Background: Evidence from clinical trials suggest anti-SARS-CoV-2 monoclonal antibodies (mABs) may reduce COVID-19-related hospitalizations. The purpose of this study was to assess the real world impact of mAB administration on COVID-19 hospitalization among patients 65 years or older.

Methods: This was a retrospective, propensity-matched cohort study that included patients aged 65 years and older who presented to the emergency department (ED) within ten days of symptom onset of mild to moderate COVID-19 infection. Outcomes were compared between those who did and did not receive mAB therapy. The primary endpoint was the rate of hospitalization for COVID-19 within 30 days of index ED visit.

Results: A total of 137 patients receiving mABs were matched to 137 controls. Hospitalization occurred in 2.9% of mAB-treated patients compared to 14.6% of patients of the standard of care (SOC) arm (OR 0.20, [95% CI 0.07-0.59]). There were zero intubations and zero deaths compared to three (2.2%) and two (1.5%) in the SOC group. Among the 223 patients receiving mAB in the overall cohort, adverse drug events occurred in 10 (4.5%).

Conclusions: Treatment with mAB therapy for mild to moderate COVID-19 was associated with a substantially reduced risk of hospitalization among patients at least 65 years of age. This article is protected by copyright. All rights reserved.

Keywords: COVID-19; anti-SARS-CoV-2 monoclonal antibodies; bamlanivimab; casirivimab +imdevimab; older adults.

Objectives: To develop a method for in vitro assembly of recombinant proteins expressed in E. coli into chimeric virus-like particles (cVLPs).

Results: A fusion protein (Bepi-Cap-A) between capsid protein (Cap) of PCV2b and B cell epitope (Bepi) of IBDV was expressed in E. Coli, and purified. For assembling them into cVLPs (Bepi-Cap-VLP), the Bepi-Cap-A was suspended in buffer C [0.03% ("%" stands for "v/v" unless otherwise indicated) polyethylene glycol, 0.4 M Tris, 10 mM β-mercaptoethanol, 5% glycerol, 0.02% (w/v) gellan gum, 0.1 M glycine, 0.03% Tween 80, 500 mM NaCl], and incubated. After centrifugation, the pellet was resuspended in buffer D [50 mM Na₂HPO₄, 50 mM NaH₂PO₄, 0.01% (w/v) gellan gum, 0.05 mM EDTA, 500 mM NaCl, 0.03% Tween 80, pH 6.5], and then dialyzed against dialysis buffer (50 mM Na₂HPO₄, 50 mM NaH₂PO₄, 500 mM NaCl, 0.03% Tween 80, pH 6.5). The procedure resulted in typical and immunogenic Bepi-Cap-VLP.

Conclusions: The data provide a method which is feasible for in vitro assembly of recombinant proteins into chimeric virus-like particles.

Keywords: B-cell epitope; Capsid protein; Chimeric virus-like particle (cVLP); Dialysis; In vitro assembly.

Redox flow batteries (RFBs) stand out as a promising energy storage system to solve the grid interconnection problems of renewable energy. Membranes play a critical role in regulating the performance of RFBs, and the selectivity is commonly controlled via either size exclusion or Donnan exclusion. Membranes typically account for 40% of the stack cost of RFBs, and it is essential to develop cost-effective membranes with high selectivity to achieve widespread application. Here, a type of membrane composed of highly abundant materials derived in nature, based on a scalable fabrication process, is reported. Moreover, high selectivity is achieved attributed to the host-guest interactions between membranes and redox species, which effectively alleviate the crossover of redox-active molecules. By incorporating starch into a chitosan matrix for zinc-iodine RFBs, the highly selective recognition of starch and chitosan (host) toward triiodide (guest) builds a "wall" to block the triiodide-based active materials, meanwhile, the conducting properties of such a membrane are not compromised. The proof-of-concept battery delivers a Coulombic efficiency of 98.6% and energy efficiency of 77.4% at a current density of 80 mA cm^-2 , showing the promise of such a novel and cost-effective membrane design beyond traditional selectivity chemistry.

Keywords: chitosan; flow batteries; host-guest chemistry; starch; zinc-iodine.

All-solid-state lithium ion batteries (ASS-LIBs) are promising due to their safety and higher energy density as compared to that of conventional LIBs. Over the next few decades, tremendous amounts of spent ASS-LIBs will reach the end of their cycle life and would require recycling in order to address the waste management issue along with reduced exploitation of rare elements. So far, only very limited studies have been conducted on recycling of ASS-LIBS. Herein, we investigate the recycling of the Li₇ La₃ Zr₂ O₁₂ (LLZO) solid-state electrolyte in a LiFePO₄ /LLZO/Li₄ Ti₅ O₁₂ system using a hydrometallurgical approach. Our results show that different concentration of the leaching solutions can significantly influence the final product of the recycling process. However, it was possible to recover relatively pure La₂ O₃ and ZrO₂ to re-synthesize the cubic LLZO phase, whose high purity was confirmed by XRD measurements.

Keywords: Li7La3Zr2O12; all-solid-state lithium-ion batteries; circular economy; hydrometallurgy; recycling.

Human induced pluripotent stem cell (hiPSC)-derived cerebral organoids (COs) can serve as an in vitro model for studying normal and pathologic human brain development. Here, we optimized existing protocols to streamline the generation of forebrain COs from hiPSCs. We employ these COs to define the impact of disease-causing mutations on cell fate, differentiation, maturation, and morphology relevant to neurodevelopmental disorders. Although limited to forebrain CO identity, this schema requires minimal external interference and is amenable to low-throughput biochemical assays. For complete details on the use and execution of this profile, please refer to Anastasaki et al. (2020) and Wegscheid et al. (2021).

Keywords: Cell Biology; Cell culture; Developmental biology; Health Sciences; Neuroscience; Organoids; Stem Cells.

Objective: Cancer is a significant cause of mortality worldwide. The diagnosis of advanced cancer affects both patients and their family caregivers. Understanding the course of both negative and positive experiences of caregiving provides a more comprehensive understanding of the caregiving experience. The study aims to identify joint trajectories of burden and esteem among family caregivers of patients with solid metastatic cancer, and to identify caregiver characteristics that predict membership for each delineated trajectory.

Methods: A prospective longitudinal study of 346 informal family caregivers of patients with solid metastatic cancer were recruited between July 2016 and December 2019. Surveys were conducted every 3 months for 2 years. We assessed caregiver burden and positive aspects of caregiving using the modified Caregiver Reaction Assessment. We estimated the joint trajectories for these outcomes using group-based multi-trajectory modelling.

Results: We identified 4 trajectories describing caregivers with 1) low burden, moderate esteem (38.3%), 2) low burden, high esteem (20.3%), 3) high burden, low esteem (16.4%), 4) high burden, high esteem (24.9%). Compared to the "low burden, high esteem" trajectory, male and non-spousal caregivers were more likely to experience high burden and esteem while caregivers from low socioeconomic status were more likely to belong to trajectories with a high burden.

Conclusion: Recognising caregivers at high risk of belonging to trajectories with high burden or low esteem may enable healthcare professionals to anticipate and provide appropriate support to mitigate the impact of negative outcomes.

Keywords: Caregiver; advanced; cancer; metastatic; oncology; primary; prospective; trajectory.

Background: A school district in Northern Ohio implemented a COVID-19 surveillance program from January 4 to May 21, 2021, as in-person school and extracurricular activities resumed.

Methods: Among 560 staff members and >6300 students, random weekly testing was performed on 563 students and weekly for 204 students participating in extracurricular activities, and 553 staff.

Results: Cases of COVID-19 were identified among 26 staff members and 23 students. Most of those infected were participating in extracurricular activities (14/23) and in the age range of 14-18. Percent positivity was low (range 0.2-2.4%) throughout the school surveillance program despite significant changes in positivity rate (2.8-19.8%).

Conclusion: This demonstrates that in a setting employing basic yet consistent mitigation strategies, there is low transmission among young children and adolescents as they return to in-person classes and activities. Maintaining layered prevention strategies implemented and sustained with fidelity can substantially limit transmission within schools.

Keywords: COVID-19; mitigation; schools; surveillance; transmission.

Objective: The COVID-19 pandemic has disproportionately impacted minority communities, yet little data exists regarding whether disparities have improved at a health system level. This study examined whether sociodemographic disparities in hospitalization and clinical outcomes changed between two temporal waves of hospitalized COVID-19 patients.

Methods: This is a retrospective cohort study of primary care patients at Mass General Brigham (a large northeastern health system serving 1.27 million primary care patients) hospitalized in-system with COVID-19 between March 1, 2020, and March 1, 2021, categorized into two 6-month "wave" periods. We used chi-square tests to compare demographics between waves, and regression analysis to characterize the association of race/ethnicity and language with in-hospital severe outcomes (death, hospice discharge, intensive unit care need).

Results: Hispanic/Latino, Black, and non-English-speaking patients constituted 30.3%, 12.5%, and 29.7% of COVID-19 admissions in wave 1 (N = 5844) and 22.2%, 9.0%, and 22.7% in wave 2 (N = 4007), compared to 2019 general admission proportions of 8.8%, 6.3%, and 7.7%, respectively. Admissions from highly socially vulnerable census tracts decreased between waves. Non-English speakers had significantly higher odds of severe illness during wave 1 (OR 1.35; 95% CI: 1.10, 1.66) compared to English speakers; this association was non-significant during wave 2 (OR 1.01; 95% CI: 0.76, 1.36).

Conclusions: Comparing two COVID-19 temporal waves, significant sociodemographic disparities in COVID-19 admissions improved between waves but continued to persist over a year, demonstrating the need for ongoing interventions to truly close equity gaps. Non-English-speaking language status independently predicted worse hospitalization outcomes in wave 1, underscoring the importance of targeted and effective in-hospital supports for non-English speakers.

Keywords: COVID-19; Disparities; Language; Race; Sociodemographic.

Respiratory system damage is the primary cause of mortality in individuals who are exposed to vesicating agents including sulfur mustard (SM). Despite these devastating health complications, there are no fielded therapeutics that are specific for such injuries. Previous studies reported that SM inhalation depleted the tracheobronchial airway epithelial stem cell (TSC) pool and supported the hypothesis, TSC replacement will restore airway epithelial integrity and improve health outcomes for SM-exposed individuals. TSC express Major Histocompatibility Complex (MHC-I) transplantation antigens which increases the chance that allogeneic TSC will be rejected by the patient's immune system. However, previous studies reported that Beta-2 microglobulin (B2M) knockout cells lacked cell surface MHC-I and suggested that B2M knockout TSC would be tolerated as an allogeneic graft. This study used a Cas9 ribonucleoprotein (RNP) to generate B2M-knockout TSC, which are termed Universal Donor Stem Cells (UDSC). Whole genome sequencing identified few off-target modifications and demonstrated the specificity of the RNP approach. Functional assays demonstrated that UDSC retained their ability to self-renew and undergo multilineage differentiation. A preclinical model of SM inhalation was used to test UDSC efficacy and identify any treatment-associated adverse events. Adult male Sprague-Dawley rats were administered an inhaled dose of 0.8 mg/kg SM vapor which is the inhaled LD₅₀ on day 28 post-challenge. On recovery day 2, vehicle or allogeneic Fisher rat UDSC were delivered intravenously (n = 30/group). Clinical parameters were recorded daily, and planned euthanasia occurred on post-challenge days 7, 14, and 28. The vehicle and UDSC treatment groups exhibited similar outcomes including survival and a lack of adverse events. These studies establish a baseline which can be used to further develop UDSC as a treatment for SM-induced airway disease.

Keywords: Cas9; inhalation; medical countermeasure; ribonucleoprotein complex; sulfur mustard; tracheobronchial epithelial tissue specific stem cell.

Introduction: The benefits of minimally invasive surgery using laparoscopy on postoperative pain and opioid use are well established. Our goal was to determine whether patients who underwent Roux-en-Y gastric bypass using a robotic approach (RA-RYGB) had lower postoperative pain and required less opioids than those undergoing laparoscopic Roux-en-Y gastric bypass (L-RYGB). Secondary outcomes evaluated included length of stay, operative time, and readmissions.

Methods and procedures: This was a retrospective cohort study from a tertiary academic medical center. Patients who underwent L-RYGB or RA-RYGB between 5/1/2018 and 10/31/2019 were included. Cases with concomitant hernia repair, chronic opioid use, and those who did not receive a TAP block or multimodal pain control were excluded. Baseline demographics were compared. Inpatient and outpatient opioid use in Morphine Milligram Equivalents (MME) and pain scores (10-point Likert scale) were compared.

Results: There were 573 RY patients included (462 L-RYGB; 111 RA-RYGB). Median and maximum inpatient pain scores were similar for L-RYGB and RA-RYGB (3.0 vs 3.1, p = 0.878; 7.0 vs 7.0, p = 0.688). Median inpatient opioid use and maximum single day use were similar for L-RYGB and RA-RYGB (40.0 MME vs. 42.0 MME, p = 0.671; 30.0 MME vs 30.0 MME, p = 0.648). Both the outpatient prescribing of opioids (50.2% vs. 42.3%, p = 0.136) and outpatient opioid MME at 2 weeks (L-RYGB 30.0 MME vs. 33.8 MME, p = 0.854) were comparable between cohorts. Patient reported pain at 2-week follow-up was significantly higher for RA-RYGB (68.1%) than L-RYGB (55.6%) (p = 0.030). RA-RYGB had a higher rate of 30-day readmission and longer operative times compared to the L-RYGB (6.3% vs 13.5%, p = 0.010; 144.5 vs 200.0 min, p < 0.001).

Conclusion: This study identified no benefit for postoperative pain or opioid requirements in patients undergoing RA-RYGB compared to L-RYGB. The RA-RYGB group was significantly more likely to report pain at the two-week follow-up.

Keywords: Bariatric surgery; Gastric bypass; Laparoscopic; Opioids; Pain scores; Postoperative pain; Robotic.

Pemphigus vulgaris is a rare immune-mediated skin disorder of the dog, usually treated with immunosuppressive medications such as oral glucocorticoids, azathioprine or ciclosporin. Herein we report the successful treatment of pemphigus vulgaris in a dog, using oclacitinib and a topical product containing fucidic acid (0.5 % w/w) and betamethasone valerate.

寻常型天疱疮是一种罕见的免疫介导性犬皮肤病, 通常使用免疫抑制药物治疗, 如口服糖皮质激素、硫唑嘌呤或环孢素。在此, 我们报告了使用奥拉替尼和含有夫西地酸(0.5%w/w)和戊酸倍他米松的外用产品成功治疗犬寻常型天疱疮。.

Le pemphigus vulgaire est une affection cutanée rare à médiation immune chez le chien, généralement traitée avec des médicaments immunosuppresseurs tels que les glucocorticoïdes oraux, l'azathioprine ou la ciclosporine. Nous décrivons ici le traitement efficace du pemphigus vulgaire chez un chien, à l'aide d'oclacitinib et d'un produit topique contenant de l'acide fucidique (0,5 % p/p) et du valérate de bétaméthasone.

Pemphigus vulgaris ist eine seltene immun-mediierte Hauterkrankung des Hundes, die in der Regel mit immunsuppressiven Medikamenten wie Glukokortikoiden per os, Azathioprin oder Ciclosporin behandelt wird. Hierin berichten wir von der erfolgreichen Behandlung eines Pemphigus vulgaris bei einem Hund mit Oclacitinib und einem topischen Produkt, welches Fucidinsäure (0,5% w/w) und Betamethason Valerat beinhaltete.

尋常性天疱瘡は、犬にみられるまれな免疫介在性皮膚疾患であり、通常、グルココルチコイド、アザチオプリン、シクロスポリンなどの免疫抑制剤による治療が行われる。今回, 我々は, オクラシチニブマレイン酸塩とフシジン酸 (0.5%w/w) およびベタメタゾン含有外用剤を用いて、犬の尋常性天疱瘡の治療に成功したことを報告する。.

O pênfigo vulgar é uma dermatopatia imunomediada dos cães, que é usualmente tratada com medicações imunossupressoras como corticoides por via oral, azatioprina ou ciclosporina. No presente estudo, relatamos o tratamento de bem sucedido de penfigp vulgaris em um cão, utilizando o oclacitinib e um produto tópico contendo ácido fusídico (0,5 % w/w) e valerato de betametasona.

El pénfigo vulgar es un trastorno inmunomediado cutáneo poco frecuente en perros, generalmente tratado con medicamentos inmunosupresores como glucocorticoides orales, azatioprina o ciclosporina. En este artículo describimos el tratamiento exitoso de pénfigo vulgar en un perro utilizando oclacitinib y un producto tópico que contiene ácido fucídico (0,5 % p/p) y valerato de betametasona.

We report an anisotropic-kinetics transformation strategy to prepare single-crystalline aluminosilicate MFI zeolites (ZSM-5) with highly open nanoarchitectures and hierarchical porosities. The methodology relies on the cooperative effect of in situ etching and recrystallization on the evolution of pure-silica MFI zeolite (silicalite-1) nanotemplates under hydrothermal conditions. The strategy enables a controllable preparation of ZSM-5 nanostructures with diverse open geometries by tuning the relative rate difference between etching and recrystallization processes. Meanwhile, it can also be extended to synthesize other heteroatom-substituted MFI zeolite nanocages. Compared with conventional ZSM-5 microcrystals, nanocrystals, and nanoboxes, the ZSM-5 nanocages with single-crystalline nature, highly open nanoarchitectures, and hierarchical porosities exhibit remarkably enhanced catalytic lifetime and low coking rate in the methanol-to-hydrocarbons (MTH) reaction.

Keywords: ZSM-5; methanol-to-hydrocarbons reaction; nanocages; open nanostructures; zeolites.

Here, we present a step-by-step protocol for three-dimensional reconstruction of astrocyte morphology, applied to the central amygdala oxytocin receptor-expressing astrocytes. This includes RNAse-free perfusion, combination of RNAscope and immunohistochemistry, and confocal imaging. This protocol provides detailed information about tissue handling and a comprehensive description of the RNAScope technique to label rat and mouse oxytocin receptor mRNA. We also describe three-dimensional reconstruction that allows the assessment of more than 70 different cellular parameters, powerful for studying astrocyte morphology and astrocyte-astrocyte interactions. For complete details on the use and execution of this protocol, please refer to Wahis et al. (2021) and Althammer et al. (2020).

Keywords: Antibody; In Situ Hybridization; Microscopy; Molecular Biology; Neuroscience.

Knowledge of anterior-posterior (AP) movement of the femoral condyles on the tibia in healthy knees serves to assess whether an artificial knee restores natural movement. Two methods for identifying AP positions and hence condylar movements include: 1) the flexion facet center (FFC), and 2) the lowest point (LP) methods. The objectives were to determine 1) agreement between the two methods, and 2) whether addition of articular cartilage and/or smoothing significantly affects AP positions. MR images of healthy knees were obtained from eleven subjects, who performed a deep knee bend under fluoroscopy. Four different MR models of the distal femur were created: femur bone, smoothed femur bone, femur bone with cartilage, and femur bone with smoothed cartilage. In the medial and lateral compartments for the femur bone with smoothed cartilage at 0 degrees flexion, mean AP positions of the LPs were 7.7 mm and 5.4 mm more anterior than those of the FFCs, respectively (p = 0.0001, p = 0.0002) and limits of agreement were plus/minus 5.5 mm. At 30 - 90 degrees flexion, the difference in mean AP positions was 1.5 mm or less and limits of agreement were plus/minus 2.4 mm. Differences in mean AP positions between model types were less than 1.3 mm for LPs and FFCs. Since adding cartilage to 3D bone models is not required to accurately determine AP positions, faster and less expensive imaging techniques such as CT can be used to generate 3D bone models.

Background: There is a paucity of knowledge about cosmetic vaginal tightening procedures; therefore, the present study aimed to describe the clinical effects of a novel combination technique of human acellular dermal matrix (HADM) and enriched platelet therapy (EPT) for the treatment of vaginal laxity.

Methods: This single-arm, observational study was conducted on 52 patients with grade II to III vaginal relaxation. HADM biological band (U-shaped) was implanted in these patients by submucosal puncture in vagina under anesthesia. This was followed by thrice administration of EPT injection, once at the time surgery followed by each dose at a time interval of one month. Patients were followed up for a period of 6 months based on Female Sexual Function Index (FSFI) and Vaginal Health Index (VHI) scores. Patient satisfaction was measured using Visual Analogue Score (VAS).

Results: About 52 women with median age of 39 years were included in the study. The average time reported to complete HADM surgery was reported as 27 minutes. Following implantation, it was found that labia minora was significantly closed and perineal length was increased from 1.5 to 2.2 cm. Moreover, there was improvement in elasticity, contractility and lubricity of vaginal mucosa. The sexual function scores from pre- to post-surgery were significantly increased (7.95 vs. 30.09; p value: <0.001). The mean VHI score also increased significantly after 6 months of treatment (mean ± S.D. before vs after treatment: 11.2 ± 3.3 vs. 19.6 ± 4.1, P < 0.0001). The mean VAS after surgery was 1.61 ± 0.31. About 96% of the patients did not feel any pain after treatment at 6-month follow-up. No adverse effects were reported in this study.

Conclusions: These findings supported that combination treatment with HADM and EPT was safe and associated with both improved vaginal laxity and sexual function. These results may provide a novel surgical technique for this prevalent and undertreated condition.

Level of evidence iv: Therapeutic Study This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Keywords: EPT; HADM; Surgical; Vaginal laxity.

Fresh tomato juice was processed by hydrodynamic cavitation (HC) at 5 to 15 psi pressures for 5-30 min. A full factorial design was applied to optimize the HC treatment of tomato juice quality. Optimal conditions were recorded at 10 psi for 10 min, which showed no significant (p < 0.05) change in lycopene content to that of freshly obtained unprocessed tomato juice (control). After processing, the retention of 93% ascorbic acid and 96.6% of total phenolic compounds (TPC) was observed. Similarly, sedimentation and viscosity were mildly affected by HC processing (89.2 and 94.4% of values in the treated sample, respectively). While pH, total soluble solids (TSS), titratable acidity (TA) of HC treated sample remained unchanged (p < 0.05). The results were also compared with the conventional thermally processed tomato juice (90 °C for 90 s). Although thermal treatment resulted in the inactivation of 92.2% of pectin methylesterase and a 5 log reduction in total plate counts, it also showed significant reductions in ascorbic acid (61.4%), TPC (72.3%), and physical properties (37.7% of SI and 83.2% viscosity). However, HC processing could achieve a maximum of 4.9% inactivation of PME and 1 log reduction at high treatment conditions, respectively (15 psi for 30 min). The shelf-life study showed more retention of bioactives and better physicochemical properties in tomato juice samples stored at 4 °C for 15 days than the control. Sensory evaluation revealed that the overall acceptability of the optimized HC treated (0.714) sample was better than the thermally treated sample (0.591). The observed results concluded that HC-treated tomato juice was comparatively better than thermally-treated tomato juice in retaining bioactive compounds. Consequently, HC constitutes a promising approach in food processing to improve and retain the beneficial properties of tomato juice.

Keywords: Bioactive compounds; Fuzzy logic; Hydrodynamic cavitation; Pectin methyl esterase; Tomato juice; Viscosity.

Aim: S-flurbiprofen plaster (SFPP) is a novel topical nonsteroidal anti-inflammatory drug (NSAID) patch. This study aimed to assess the efficacy and safety of SFPP in knee osteoarthritis (OA) patients compared to diclofenac gel.

Methods: This study was a multicenter, randomized, active-controlled, open-label, non-inferiority phase III trial. There were 311 enrolled patients treated by SFPP or diclofenac gel for 2 weeks. The primary efficacy outcome was the knee pain when rising from the specially arranged chair assessed by visual analog scale (rVAS). The other efficacy outcomes were clinical symptoms, pain on walking, global assessment by both investigator and patient, and use/non-use of the rescue drugs during the treatment period. Adverse events (AEs) were evaluated as the safety outcome.

Results: The least-squares mean (95% CI) of ΔrVAS at the end of the study was 41.52 (39.16-43.88) mm in the SFPP group and 36.01 (33.69-38.33) mm in the diclofenac gel group, with a between-group difference of 5.51 (2.20-8.82), indicating non-inferiority. There were statistically significant differences between the groups in rVAS, clinical symptoms, pain on walking, and the global assessment by both investigator and patient. The incidence rate of AEs in the SFPP group was 5.8%, and there was no statistically significant difference from that in the diclofenac gel group (5.2%). Most of the AEs were mild, and no AE led to discontinuation.

Conclusion: Non-inferiority of SFPP to diclofenac gel was demonstrated in the efficacy for pain on rising from a chair. SFPP was also well-tolerated in knee OA patients.

Keywords: S-flurbiprofen; nonsteroidal anti-inflammatory drug; osteoarthritis; pain; patch; randomized controlled study; visual analog scale.

Acute kidney injury (AKI) is a common clinical syndrome and an independent risk factor of chronic kidney disease and end-stage renal failure. At present, the treatments of AKI are still very limited and the morbidity and mortality of AKI are rising. Non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs and circular RNAs (circRNAs), are RNAs that are transcribed from the genome, but not translated into proteins. It has been widely reported that ncRNA is involved in AKI caused by ischemia reperfusion injury (IRI), drugs and sepsis through different molecular biological mechanisms, such as apoptosis and oxidative stress response. Therefore, ncRNAs are expected to become a new target for clinical prevention and treatment of AKI and a new biomarker for early warning of the occurrence and prognosis of AKI. Here, the role and mechanism of ncRNA in AKI and the research progress of ncRNA as biomarkers are reviewed.

The control of endogenous proteins activity with light inside live cells is helpful for the high spatiotemporal probing of their dynamic roles. Herein, we report the first small-molecule-ligand-directed caging approach to control the endogenous human O 6 -alkylguanine-DNA alkyltransferases (AGT) activity with light, and the caged AGT is constructed from the native intracellular AGT. The photo-responsive O 6 -benzylguanine derivative O 6 -NBG3 is developed to site-specifically cage the AGT's catalytic cysteine residue, and the light irradiation on-demand restores AGT's activity in vitro, in bacteria, and in mammalian cells. With O 6 -NBG3, the alkylated AGT is dealkylated for the first time to recover the DNA repair activity in breast cancer MCF-7 cells by the dose-dependent light irradiation. This decaging strategy enables the localized modulation of endogenous AGT activity in high temporal precision without genetic engineering, which holds great potential for therapeutic applications.

Keywords: DNA alkyltransferases; endogenous protein modulation; photodecaging; small molecule ligands.

The kidney is one of the main target organs involved in hypertension, and it regulates water and salt metabolism, blood volume and vascular resistance. High salt intake induces salt and water retention, persistent endothelial dysfunction and elevation of blood pressure in salt sensitive individuals. Dahl salt sensitive (Dahl-SS) rats, as a classic animal model for salt sensitive hypertension, have many similar stably inherited physiological characteristics to human with salt sensitive hypertension, such as salt sensitivity, hyperlipidemia, insulin resistance, renal failure, increased urinary protein secretion and low plasma renin activity. Based on renal physiology and biochemistry researches and multi-omics analyses in Dahl-SS rats, this review will summarize the relationship between salt sensitive hypertension and renal redox, NO, amino acids, glucose and lipid metabolism.

Human amniotic epithelial cells (hAECs) are epithelial cells located on the placental amnion near the fetus. Different from other placental-derived stem cells, hAECs are derived from embryonic epiblast, and have been considered as seed cells for regenerative medicine. hAECs possess embryonic stem cell-like multi-differentiation capabilities and adult stem cell-like immunomodulatory properties. Compared with other types of stem cells, special properties of hAECs make them unique, including easy isolation, abundant cell numbers, non-tumorigenicity after transplantation, and the obviation of ethical debates. During the past two decades, the therapeutic potential of hAECs has been extensively investigated in various diseases. Accumulating evidence has demonstrated that hAECs contribute to repairing and remodeling the function of damaged tissues and organs through different molecular mechanisms. This article provides an in-depth review of the biological characteristics of hAECs, summarizes the research status of hAECs, and discusses the clinical application prospects of hAEC-based cell therapy.

Four types of primary cells-dermal fibroblasts, dermal microvascular endothelial cells, epidermal keratinocytes, and epidermal melanocytes-can be isolated simultaneously from a single human skin sample, without the use of xenogeneic murine feeder cells. This protocol describes the procedures for isolation of these cells from adult full-thickness skin obtained from surgical discard tissue. The cells isolated using this protocol contain stem cell populations and are competent to form functional skin tissue in three-dimensional reconstructed skin models. For complete details on the use and execution of this profile, please refer to Supp et al. (2002), Boyce et al. (2015), Boyce et al. (2017a), Boyce et al. (2017b), and Supp et al. (2019).

Keywords: Cell Biology; Cell culture; Cell isolation; Stem Cells; Tissue Engineering.