Renal protective and immunoregulatory effects of Lactobacillus casei strain Shirota in nephropathy-prone mice.

Introduction: The incidence of severe acute kidney injury (AKI) is considerably high worldwide. A previous study showed that gut microbial dysbiosis was a hallmark of AKI in mice. Whether the probiotic Lactobacillus casei strain Shirota (LcS) plays a role in kidney disease, particularly AKI, remains unclear. Methods: To investigate the effects of LcS on kidney injury, tubule-specific conditional von Hippel-Lindau gene-knockout C57BL/6 mice (Vhlhdel/del mice) were supplemented without (Ctrl) or with probiotics (LcS) in Experiment 1, and their lifespan was monitored. Additionally, the Vhlhdel/+ mice were supplemented without (Ctrl and AA) or with probiotics (LcS and LcS + AA) in Experiment 2. Probiotic LcS (1 × 109 colony-forming units) was supplemented once daily. After 4 weeks of LcS supplementation, AA and LcS + AA mice were administered aristolochic acid (AA; 4 mg/kg body weight/day)-containing purified diet for 2 weeks to induce AA nephropathy before sacrifice. Results: Supplementation of LcS significantly prolonged the lifespan of Vhlhdel/del mice, suggesting a potential renal protective effect. AA induced-nephropathy increased not only the indicators of renal dysfunction and injury, including urinary protein and kidney injury molecule (KIM)-1, serum blood urea nitrogen (BUN) and creatinine, but also serum interleukin (IL)-6 levels, renal macrophage infiltrations, and pathological lesions in Vhlhdel/+ mice. LcS supplementation significantly reduced urinary protein and KIM-1 levels, serum BUN and IL-6 levels, and renal M1 macrophages, tissue lesions, and injury scores. We also found that LcS maintained gut integrity under AA induction and increased intestinal lamina propria dendritic cells. Furthermore, LcS significantly reduced pro-inflammatory IL-17A and upregulated anti-inflammatory IL-10 production by immune cells from intestinal Peyer's patches (PP) or mesenteric lymph nodes (MLN), and significantly increased IL-10 and reduced IL-6 production by splenocytes. Conclusion: Prior supplementation with probiotic LcS significantly alleviated the severity of renal injury. This renal protective effect was partially associated with the enhancements of intestinal and systemic anti-inflammatory immune responses, suggesting that LcS-induced immunoregulation might contribute to its renal protective effects.

Valley Spin-Polarization of MoS2 Monolayer Induced by Ferromagnetic Order in an Antiferromagnet.

Transition metal dichalcogenide (TMD) monolayers exhibit unique valleytronics properties due to the dependency of the coupled valley and spin state at the hexagonal corner of the first Brillouin zone. Precisely controlling valley spin-polarization via manipulating the electron population enables its application in valley-based memory or quantum technologies. This study uncovered the uncompensated spins of the antiferromagnetic nickel oxide (NiO) serving as the ferromagnetic (FM) order to induce valley spin-polarization in molybdenum disulfide (MoS2) monolayers via the magnetic proximity effect (MPE). Spin-resolved photoluminescence spectroscopy (SR-PL) was employed to observe MoS2, where the spin-polarized trions appear to be responsible for the MPE, leading to a valley magnetism. Results indicate that local FM order from the uncompensated surface of NiO could successfully induce significant valley spin-polarization in MoS2 with the depolarization temperature approximately at 100 K, which is relatively high compared to the related literature. This study reveals new perspectives in that the precise control over the surface orientation of AFMs serves as a crystallographic switch to activate the MPE and the magnetic sustainability of the trion state is responsible for the observed valley spin-polarization with the increasing temperature, which promotes the potential of AFM materials in the field of exchange-coupled Van der Waals heterostructures.

Demystifying gene(tic) therapies.

This article summarizes the discussion from a session entitled "Demystifying gene therapies" that was held at the joint RE(ACT) congress and IRDiRC conference, 14-15 March 2023 in Berlin, Germany. The focus of this session was to discuss the changing landscape of genetic therapies and whether current resources exist to provide adequate education to stakeholders, such as researchers, clinicians, patient advocates, legislators, as well as the patients and their families. The goal of this article is not to provide a comprehensive overview of the current landscape in genetic therapies, but rather to highlight resources that may be useful to help "demystify" the myriad of genetic therapeutic approaches.

"What you Say Matters": Review of Clinical Outcome of Advanced Medical Directives Between Cancer and Non-cancer Patients in a Chinese Culture Society.

INTRODUCTION: Advance medical directives (AMD) are statements made by individuals indicating the life-sustaining treatment that they would refuse in the future when they lost their mental capacity for medical decisions. While the proposal for the AMD legislation is ongoing locally in Hong Kong SAR, there are limited reviews on the clinical outcomes associated with it. OBJECTIVE: To provide a comprehensive review on clinical outcomes of signed AMD. METHODOLOGY: Retrospective, multi-center study, which includes AMD signed within five cluster hospitals. Records of signed AMD from 1st JAN 2020 to 31st DEC 2022 were retrieved from a central registry. Clinical information of each patient was obtained from the electronic patient record. RESULT: 456 patients with documented AMD were included in the study. 91.6% of AMD were signed by palliative care (PC) team. Majority (74.6%) of the patients were accompanied by family members or friends when AMD were signed. The concordance rate between the AMD and the medical care received was 89.5%. No patient revoked their AMD. Cancer and non-cancer patients showed similar rates of AMD concordance, frequency of Accident & Emergency Department (AED) visits or acute ward admissions, duration of hospital stays in the 30 days before death, and prevalence of receiving invasive or intensive treatments. CONCLUSION: Our study demonstrated that PC team currently plays a pivotal role in AMD completion, and AMD remains important in ensuring patients' care preferences are executed across different medical conditions. With the upcoming AMD legislation in Hong Kong SAR, adequate promotion and education should be launched.

Mechanistic insights into bismuth(iii) inhibition of SARS-CoV-2 helicase.

The COVID-19 pandemic caused by SARS-CoV-2 resulted in a global public health crisis. In addition to vaccines, the development of effective therapy is highly desirable. Targeting a protein that plays a critical role in virus replication may allow pan-spectrum antiviral drugs to be developed. Among SARS-CoV-2 proteins, helicase (i.e., non-structural protein 13) is considered as a promising antiviral drug target due to its highly conserved sequence, unique structure and function. Herein, we demonstrate SARS-CoV-2 helicase as a target of bismuth-based antivirals in virus-infected mammalian cells by a metal-tagged antibody approach. To search for more potent bismuth-based antivirals, we further screened a panel of bismuth compounds towards inhibition of ATPase and DNA unwinding activity of nsp13 and identified a highly potent bismuth compound Bi(5-aminotropolonate)3, namely Bi(Tro-NH2)3 with an IC50 of 30 nM for ATPase. We show that bismuth-based compounds inhibited nsp13 unwinding activity via disrupting the binding of ATP and the DNA substrate to viral helicase. Binding of Bi(iii) to nsp13 also abolished the interaction between nsp12 and nsp13 as evidenced by immunofluorescence and co-immunoprecipitation assays. Finally, we validate our in vitro data in SARS-CoV-2 infected mammalian cells. Notably, Bi(6-TG)3 exhibited an EC50 of 1.18 ± 0.09 µM with a selective index of 847 in VeroE6-TMPRSS2 infected cells. This study highlights the important role of helicase for the development of more effective antiviral drugs to combat SARS-CoV-2 infection.

Enhancing nursing students' clinical competency using a multi-patient simulation learning model: A randomized controlled study.

BACKGROUND: For nurses, clinical competency is paramount in ensuring that patients receive safe, high-quality care. Multi-patient simulation (MPS) in nursing education is gaining attention, and evidence shows its suitability for real-life situations. MPS can be an effective solution for nurses' continuing clinical education. OBJECTIVES: This project compares the effectiveness of MPS (involving both a standardized patient and a high fidelity simulator) and a single high-fidelity simulation (single HFS; only involving a high fidelity simulator) for enhancing the clinical competency of nursing students. DESIGN: A stratified, permuted, block randomized controlled study design was used. SETTINGS AND PARTICIPANTS: Sixty undergraduate nursing students in years 3, 4, and 5 were selected to participate. Subgroups with each comprising three undergraduate nursing students from different years were formed. METHODS: The participants were randomized to receive either an MPS (intervention group) or single HFS (control group) for 1 day; they later received the same intervention after a 30-day washout period. One objectively measured questionnaire and two self-reported questionnaires were used to measure clinical competency: the Creighton Competency Evaluation Instrument (CCEI), Clinical Competence Questionnaire (CCQ), and Simulation Effectiveness Tool - Modified Questionnaire (SET-M). RESULTS: The results revealed significant between-group differences. Specifically, the intervention group showed greater improvement than the control group in both the CCQ (linear contrast [d] = 71.4; 95 % confidence interval [CI] = 53.407, 89.393; P < 0.001) and CCEI total scores (d = 7.17; 95 % CI = 5.837, 8.503; P < 0.001). The SET-M results indicated that 85 % of the participants (n = 51) strongly agreed that they felt more confident about performing a patient handover to the healthcare team after the simulation. CONCLUSIONS: The study findings indicated that both the MPS and single HFS effectively enhanced students' clinical competency. However, MPSs have superior educational outcomes relative to traditional single HFSs.

A do it yourself (DIY) point-of-care wrist ultrasound phantom for joint access training.

BACKGROUND: Joint access is essential for arthrocentesis, or joint aspiration of fluids. Joint treatments that are not performed properly can result in avoidable patient issues such as damage to the muscles, tendons, and blood vessels surrounding the joint. The use of ultrasound has become the gold standard for this procedure and proven to be a support in the skill learning process. However, success with this equipment, particularly in small joints like the wrist, depends on a clinician's capacity to recognize the crucial landmarks that guide these procedures. Prior to executing on a real patient, task trainers have proven to be an effective way for doctors to practice and prepare for procedures. However, shortcomings of current solutions include high purchase costs, incompatibility with ultrasound imaging, and low reusability. In addition, since this is a procedure that is not performed frequently, there may not be space or resources available in healthcare facilities to accommodate one at the point of care. This study aimed to close the existing gap by developing a DIY ultrasound compatible task trainer for wrist joint access training. RESULTS: We developed a novel ultrasound compatible wrist joint model that can be made from sustainable materials and reusable parts, thus reducing the costs for acquisition and environmental impact. Our model, which was produced utilizing small-batch production methods, is made up of 3D-printed bones enclosed in an ultrasound-compatible gelatin mixture. It can be easily remade after each practice session, removing needle tracks that are visible under ultrasound for conventional phantoms. The ultrasonic properties of this model were tested through pixel brightness analysis and visual inspection of simulated anatomical structures. CONCLUSION: Our results report the advantages and limitations of the proposed model regarding production, practice, and ultrasound compatibility. While future work entails the transfer to patients of the same skill, this reusable and replicable model has proven, when presented to experts, to be successful in representing the physical characteristics and ultrasound profile of significant anatomical structures. This novel DIY product could be an effective alternative to teach procedures in the context of resource-restrained clinical simulation centers.

Dried Blood Spot Postmortem Metabolic Autopsy With Genotype Validation for Sudden Unexpected Deaths in Infancy and Childhood in Hong Kong.

Background Inborn errors of metabolism (IEM) are collectively rare but potentially preventable causes of sudden unexpected death (SUD) in infancy or childhood, and metabolic autopsy serves as the final tool for establishing the diagnosis. We conducted a retrospective review of the metabolic and molecular autopsy on SUD and characterized the biochemical and genetic findings. Methodology A retrospective review of postmortem metabolic investigations (dried blood spot acylcarnitines and amino acid analysis, urine metabolic profiling where available, and next-generation sequencing on a panel of 75 IEM genes) performed for infants and children who presented with SUD between October 2016 and December 2021 with inconclusive autopsy findings or autopsy features suspicious of underlying IEM in our locality was conducted. Clinical and autopsy findings were reviewed for each case. Results A total of 43 infants and children aged between zero days to 10 years at the time of death were referred to the authors' laboratories throughout the study period. One positive case of multiple acyl-CoA dehydrogenase deficiency was diagnosed. Postmortem reference intervals for dried blood spot amino acids and acylcarnitines profile were established based on the results from the remaining patients. Conclusions Our study confirmed the importance of metabolic autopsy and the advantages of incorporating biochemical and genetic testing in this setting.

A Metal-Free Cycloaddition of α-Diazoacetates with Amino Acid-Derived NHPI Esters for the Facile Synthesis of 1,2,4-Triazoles.

1,2,4-Triazoles are privileged scaffolds for many pharmaceuticals, and methods for structurally diverse compound libraries are of current interest. Here we report an efficient coupling of α-diazoacetates with amino acid-derived alkyl N-hydroxy phthalimide esters, under metal-free conditions involving 1,8-diazabicyclo(5.4.0)undec-7-ene as the base, with which highly functionalized 1,2,4-triazoles can be obtained in excellent yields with remarkable functional group tolerance. Preliminary studies revealed that 1,2,4-triazole 3a exhibits potent inhibition of tyrosinase activities in melanoma B16F10 cell lines, demonstrating promising skin-whitening properties.

The Hippo-YAP/TAZ-TEAD axis promotes multipotency in bone marrow stromal cells.

The mechanisms by which bone marrow stromal cells (BMSCs) maintain multilineage potency in vitro remain elusive. To identify the transcriptional regulatory circuits that contribute to BMSC multipotency, we performed paired single-nucleus multiomics of the expansion of freshly isolated BMSCs and of BMSCs undergoing tri-lineage differentiation. By computationally reconstructing the regulatory programs associated with initial stages of differentiation and early expansion, we identified the TEAD family of transcription factors, which is inhibited by Hippo signaling, as highly active in the BMSC in vitro multipotent state. Pharmacological inhibition of TEAD enhanced BMSC osteogenic and adipogenic differentiation, whereas its activation maintained BMSCs in an undifferentiated state, supporting a model whereby isolation of BMSCs coincides with a TEAD-controlled transcriptional state linked to multipotency. Our study highlights the Hippo pathway as a pivotal regulator of BMSC multipotency, and our regulatory network inferences are a reservoir of testable hypotheses that link transcription factors and their regulons to specific aspects of BMSC behavior.

Transurethral En Bloc Resection Versus Standard Resection of Bladder Tumour: A Randomised, Multicentre, Phase 3 Trial.

BACKGROUND AND OBJECTIVE: Conventionally, standard resection (SR) is performed by resecting the bladder tumour in a piecemeal manner. En bloc resection of the bladder tumour (ERBT) has been proposed as an alternative technique in treating non-muscle-invasive bladder cancer (NMIBC). The objective of this study is to investigate whether ERBT could improve the 1-yr recurrence rate of NMIBC, as compared with SR. METHODS: A multicentre, randomised, phase 3 trial was conducted in Hong Kong. Adults with bladder tumour(s) of ≤ 3cm were enrolled from April 2017 to December 2020, and followed up until 1 yr after surgery. Patients were randomly assigned to receive either ERBT or SR in a 1:1 ratio. The primary outcome was 1-yr recurrence rate. A modified intention-to-treat analysis on patients with histologically confirmed NMIBC was performed. The main secondary outcomes included detrusor muscle sampling rate, operative time, hospital stay, 30-d complications, any residual or upstaging of disease upon second-look transurethral resection, and 1-yr progression rate. KEY FINDINGS AND LIMITATIONS: A total of 350 patients underwent randomisation, and 276 patients were histologically confirmed to have NMIBC. At 1 yr, 31 patients in the ERBT group and 46 in the SR group developed recurrence; the Kaplan-Meier estimate of 1- yr recurrence rates were 29% (95% confidence interval, 18-37) in the ERBT group and 38% (95% confidence interval, 28-46) in the SR group (p = 0.007). Upon a subgroup analysis, patients with 1-3 cm tumour, single tumour, Ta disease, or intermediate-risk NMIBC had a significant benefit from ERBT. None of the patients in the ERBT group and three patients in the SR group developed progression to muscle-invasive bladder cancer; the Kaplan-Meier estimates of 1-yr progression rates were 0% in the ERBT group and 2.6% (95% confidence interval, 0-5.5) in the SR group (p = 0.065). The median operative time was 28 min (interquartile range, 20-45) in the ERBT group and 22 min (interquartile range, 15-30) in the SR group (p < 0.001). All other secondary outcomes were similar in the two groups. CONCLUSIONS AND CLINICAL IMPLICATIONS: In patients with NMIBC of ≤ 3cm, ERBT resulted in a significant reduction in the 1-yr recurrence rate when compared with SR. The study results support ERBT as the first-line surgical treatment for patients with bladder tumours of≤ 3cm.

Cardiopulmonary Resuscitation Without Aortic Valve Compression Increases the Chances of Return of Spontaneous Circulation in Out-of-Hospital Cardiac Arrest: A Prospective Observational Cohort Study.

OBJECTIVES: Following current cardiopulmonary resuscitation (CPR) guidelines, which recommend chest compressions at "the center of the chest," ~50% of patients experiencing out-of-hospital cardiac arrest (OHCA) undergo aortic valve (AV) compression, obstructing blood flow. We used resuscitative transesophageal echocardiography (TEE) to elucidate the impact of uncompressed vs. compressed AV on outcomes of adult patients experiencing OHCA. DESIGN: Prospective observational cohort study. SETTING: Single center. PATIENTS: This study included adult OHCA patients undergoing resuscitative TEE in the emergency department. Patients were categorized into AV uncompressed or AV compressed groups based on TEE findings. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was sustained return of spontaneous circulation (ROSC). The secondary outcomes included end-tidal co2 (Et co2 ) during CPR, any ROSC, survival to ICU and hospital discharge, post-resuscitation withdrawal, and favorable neurologic outcomes at discharge. Additional analyses on intra-arrest arterial blood pressure (ABP) were also conducted. The sample size was pre-estimated at 37 patients/group. From October 2020 to January 2023, 76 patients were enrolled, 39 and 37 in the AV uncompressed and AV compressed groups, respectively. Intergroup baseline characteristics were similar. Compared with the AV compressed group, the AV uncompressed group had a higher probability of sustained ROSC (53.8% vs. 24.3%; adjusted odds ratio [aOR], 4.72; p = 0.010), any ROSC (56.4% vs. 32.4%; aOR, 3.30; p = 0.033), and survival to ICU (33.3% vs. 8.1%; aOR, 6.74; p = 0.010), and recorded higher initial diastolic ABP (33.4 vs. 11.5 mm Hg; p = 0.002) and a larger proportion achieving diastolic ABP greater than 20 mm Hg during CPR (93.8% vs. 33.3%; p < 0.001). The Et co2 , post-resuscitation withdrawal, and survival to discharge revealed no significant intergroup differences. No patients were discharged with favorable neurologic outcomes. Uncompressed AV seemed critical for sustained ROSC across all subgroups. CONCLUSIONS: Absence of AV compression during OHCA resuscitation is associated with an increased chance of ROSC and survival to ICU. However, its effect on long-term outcomes remains unclear.

Extending the coverage of user-diversified IM-DD PON by FDM: a mathematical model with experimental verification.

Future passive optical networks (PONs) call for more flexibility to support diversified users with various rate demands and link qualities. Using traditional time-division multiplexing (TDM), the concept of a flexible rate PON was proposed to accommodate more users with link diversity by rate adaptation. In this Letter, we reveal the PON coverage can be further extended through frequency-division multiplexing (FDM) in the presence of multiuser diversity, namely, (i) there exist users with frequency-dependent link conditions and (ii) the link conditions exhibit disparity among users. We build a mathematical model and propose an optimization algorithm based on the binary tree search to optimize diversity gain. We experimentally verify its feasibility by studying the diversity gain concerning chromatic dispersion, optical path loss, and signal-to-noise ratio (SNR) variation in a 200G-class intensity-modulation direct-detection (IM-DD) system.

Experimental Ecosystem Eutrophication Causes Offsetting Effects on Emissions of CO2, CH4, and N2O from Agricultural Reservoirs.

Despite decades of research and management efforts, eutrophication remains a persistent threat to inland waters. As nutrient pollution intensifies in the coming decades, the implications for aquatic greenhouse gas (GHG) emissions are poorly defined, particularly the responses of individual GHGs: carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O). The biogeochemical controls of each gas can differ, making it difficult to predict the overall effect of nutrient pollution on the net radiative forcing of aquatic ecosystems. Here, we induced eutrophication of small nitrogen (N)-limited agricultural reservoirs and measured changes in diffusive GHG emissions within a before-after-control-impact (BACI) study design during June to September 2021. Each gas exhibited a unique response to 300% increases in primary production, with a shift from an overall CO2 source to a sink, a modest increase in N2O flux, and, unexpectedly, no significant change in CH4 emissions. The lack of net directional change in CO2-equivalent GHG emissions in fertilized reservoirs during the summer contrasts findings from empirical studies of eutrophic lakes. Our findings illustrate the difficulty in extrapolating among different sized ecosystems and suggest that forecast 2-fold increases in agricultural N fertilization by 2050 may not result in consistently elevated GHG emissions during summer, at least from small reservoirs in continental grassland regions.

Perception of primary care doctors towards telemedicine in Kuching, Sarawak: A cross-sectional study.

Introduction: Telemedicine is the provision of healthcare remotely via information and communications technology (ICT). This study aimed to assess the familiarity and factors related to the perception towards telemedicine and the willingness to practise telemedicine among primary care doctors. Methods: A multi-centre cross-sectional study was conducted prospectively at all public healthcare clinics across Kuching, Sarawak. A questionnaire was adapted and modified from an overseas validated questionnaire, consisting of four parts: demographic data, familiarity towards telemedicine, factors related to the perception of telemedicine and willingness to implement telemedicine. Results: A total of 131 doctors were recruited. Of them, 43.5% had never interacted with patients via email, WhatsApp or Telegram, while 68.7% had never attended any conferences, speeches or meetings regarding telemedicine. The doctors had low familiarity towards guidelines, technology and medical applications of telemedicine. The majority agreed on the ability of telemedicine to save patients' time and money, the potential of ICT in healthcare and the necessity during a pandemic but perceived the possibility of technical difficulties. The doctors who had experience in interacting with patients via email, WhatsApp or Telegram (P=0.001) and those who had ≤8 years of working experience (P=0.04) had a significantly better perception towards telemedicine. Conclusion: Although the familiarity towards telemedicine among public primary care doctors is low, their perception is good in a majority of areas. Adequate technological support and continuous education on telemedicine and its guidelines, especially medicolegal issues, are imperative to adopt and propagate telemedicine in primary care.

Phytoplankton Community Integrity Index (PCII) - A potential supplementary tool for evaluating nutrient enrichment status of Hong Kong marine waters.

Diagnosis of eutrophication requires evidence of disturbance to the balance of organisms. We describe a tool, the Plankton Community Integrity Index (PCII), derived from the Plankton Index (PI) for tracking change in the seasonal patterns of abundance of diatom and dinoflagellate lifeforms when plotted in state space. The tool uses a nutrient-minimum reference period to interpret PCII values as status indicators, with values close to 1 indicating "High" status and 0.6 a Biological Water Quality Criterion (BioWQC) target set at the "Fair"/"Good" status boundary. It has been applied to Hong Kong marine waters, using data from monthly samples from 1995 through 2021. A preliminary analysis, required for the PI method, confirmed monsoonal seasonality in the diatom lifeform. In 5 of the 9 water bodies examined, PCII time series correlated with those of Total Inorganic Nitrogen (TIN). Since 2020, all Water Control Zones met the operationally defined BioWQC target.

Salinity causes widespread restriction of methane emissions from small inland waters.

Inland waters are one of the largest natural sources of methane (CH4), a potent greenhouse gas, but emissions models and estimates were developed for solute-poor ecosystems and may not apply to salt-rich inland waters. Here we combine field surveys and eddy covariance measurements to show that salinity constrains microbial CH4 cycling through complex mechanisms, restricting aquatic emissions from one of the largest global hardwater regions (the Canadian Prairies). Existing models overestimated CH4 emissions from ponds and wetlands by up to several orders of magnitude, with discrepancies linked to salinity. While not significant for rivers and larger lakes, salinity interacted with organic matter availability to shape CH4 patterns in small lentic habitats. We estimate that excluding salinity leads to overestimation of emissions from small Canadian Prairie waterbodies by at least 81% ( ~ 1 Tg yr-1 CO2 equivalent), a quantity comparable to other major national emissions sources. Our findings are consistent with patterns in other hardwater landscapes, likely leading to an overestimation of global lentic CH4 emissions. Widespread salinization of inland waters may impact CH4 cycling and should be considered in future projections of aquatic emissions.

Navigating changes: A qualitative study exploring the health-related quality of life of breast cancer survivors during the coronavirus disease 2019 pandemic.

AIMS: To explore the impact of the coronavirus disease 2019 pandemic on the health-related quality of life (HRQoL) of breast cancer survivors. DESIGN: We utilized a qualitative descriptive approach to facilitate interviews among 25 participants, all of whom are survivors of breast cancer and have received treatment in Hong Kong within the preceding 3 years. METHODS: Content analysis was performed to understand how patients' HRQoL views and experiences changed during coronavirus disease 2019 pandemic. RESULTS: The results included six themes delineating the impact of the coronavirus disease 2019 pandemic: (i) survivor sensitivities in pandemic times, (ii) coping and conditioning in pandemic times, (iii) transforming work and home dynamics in pandemic times, (iv) cognitive resilience and adaptation to the COVID-19 protective measures, (v) social resilience in pandemic times and (vi) healthcare adaptation and coping in pandemic times. CONCLUSION: This study provides insights into the experiences and challenges of breast cancer survivors during the coronavirus disease 2019 pandemic. Some survivors had new physical and psychological symptoms, including fear and anxiety, isolation, pain, lymphoedema and burnout, which potentially have long-term impact upon HRQoL. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: This study highlights the unique challenges faced by breast cancer survivors during the coronavirus disease 2019 pandemic, including accessing healthcare services and the impact of social isolation. Healthcare providers should consider the holistic needs of breast cancer survivors in the provision of health care and develop supportive interventions, including telehealth services and online support groups, to address these challenges and improve their HRQoL. IMPACT: Surgery aimed at treating breast cancer or reducing its risk generally influences the appearance of breast areas and donor sites. The continuing effects of these changes on body image and HRQoL are well-reported, although studies have ineffectively examined the initial experiences of women regarding their postoperative appearance, particularly during the pandemic. REPORTING METHOD: The checklist of consolidated criteria for reporting qualitative research (COREQ) was utilized. PATIENT OR PUBLIC CONTRIBUTION: A small selection on breast cancer survivors contributed to the design of this study, in particular the content of the semi-structured interviews.

IL-21, not IL-17A, exacerbates murine primary biliary cholangitis.

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease caused by intrahepatic bile duct injuries, resulting in fibrosis, cirrhosis, and eventually liver failure. T helper (Th) 17 cells are proposed to involve in the pathogenesis of PBC. However, how and which Th17 cell-derived cytokines affect PBC remains unclear. In this study, we investigated the effects of Th17 effector cytokines, including interleukin (IL)-17A, IL-17F, and IL-21 in PBC using a xenobiotic-induced mouse model of autoimmune cholangitis (inducible chemical xenobiotic models of PBC) treated with cytokine-expressing adeno-associated virus. Our results showed that administration of IL-17A, the well-known main cytokine produced by Th17 cells, did not augment liver inflammation or fibrosis. In contrast, we noted IL-17A-treated mice had lower hepatic Th1 cell numbers and higher hepatic CD11b+Ly6G+ polymorphonuclear myeloid-derived suppressor cell numbers. IL-17F did not alter liver inflammation or fibrosis. However, the administration of IL-21 exacerbated liver inflammatory responses and portal cell infiltration. IL-21 markedly increased the numbers of activated CD8+ T cells and liver tissue-resident memory CD8+ T cells. Moreover, IL-21 aggravates liver fibrosis in mice with autoimmune cholangitis. These results emphasized that not IL-17A but IL-21 in Th17 cell-derived cytokines affected the pathogenesis of PBC. IL-21 enhanced liver inflammation and progression to fibrosis by enhancing the numbers and effector activities of CD8+ T cells. Delineation of the effects of different Th17 effector cytokines in PBC offers clues for developing new therapeutic approaches.

Unveiling the immune system aging in single-cell resolution.

This commentary investigates the findings presented in the article by Yang et al. in 2023, published in the Journal of Leukocyte Biology. This commentary first summarizes the spatial-temporal dynamics of regulatory T cells derived from mice (Tabula Muris Senis) of different ages (3, 18, and 24 mo) at different anatomic niches like lymph nodes and bone marrow. We also reported possible combinations of receptor-ligand interactions among T follicular regulatory cells, T follicular helper cells, and germinal center B cells, such as the calmodulin/Fas axis and PSGL-1/L-selectin axis. Then, we have elaborated on the significance of understanding aging regulatory T cells and offered some possible future research directions for Yang et al., contributing to a critical analysis of their recent study. Building on these foundations, further investigations and studies can be conducted to delve deeper into the mechanisms by which regulatory T cells influence health upon aging, potentially unveiling novel therapeutic targets to ameliorate age-related pathogenicity.