Search

Fang-Fang Lin,1 Wei-Yuan Yang,1 Jun-Xiang Zhou,1 Luo-Yuan Cao,2 Ling-Ling Huang1 1Department of Rehabilitation, Ningde Municipal Hospital Affiliated to Ningde Normal University, Ningde, 352000, People’s Republic of China; 2Department of Central Laboratory, Ningde Municipal Hospital Affiliated to Ningde Normal University, Ningde, 352000, People’s Republic of ChinaCorrespondence: Jun-Xiang Zhou; Wei-Yuan Yang, Department of Rehabilitation, Ningde Municipal Hospital Affiliated to Ningde Normal University, No. 7 of Jiaocheng North Road, Jiaocheng District, Ningde, 352000, People’s Republic of China, Tel +86-15159370026 ; +86-13004929861, Email zhoujunxiangz@126.com; weiyuanyang9@126.comObjective: We investigated the clinical characteristics, fall outcomes, and related factors of falls in patients who were hospitalized in the rehabilitation department, and explored strategies to reduce the incidence of falls and prevent falls in patients.Methods: Data from 60 patients who fell in the rehabilitation department between 2016 and 2021 were analyzed for clinical characteristics, associated factors, incidence of falls, injuries, and patient demographics. Under the random stratified sampling method, 60 patients who did not fall during the same period were selected as the control group, and relevant data was collected. Measurement data were compared using an independent sample t-test. Enumeration data were compared using chi-squared (χ2) test was employed to compare these data between the two groups. Non-parametric data were analyzed using the Mann–Whitney U-test. Factors potentially influencing falls were scrutinized through both univariate and binary logistic regression analyses.Results: The median annual incidence of falls among patients who were hospitalized in the rehabilitation department was 0.04%, while the overall fall injury rate was 60%. Falls were most prevalent within 30 days of hospitalization (71.67%). The most common fall-related condition was craniocerebral disease (83.33%). The incidents of falls location of fall were mainly reported in nearby areas of rehabilitation ward (70%). Most accidents occurred between 7:00 a.m.– 12:00 p.m. and 3:01 p.m.– 6:00 p.m. (63.33%), and dyskinesia was the most common cause of falls (71.67%). There were 39 patients (65.00%) with Barthel Index (BI) scores ranging between 40– 60.Conclusion: Patients in the rehabilitation department had a greater incidence of falls and fall injuries. Within 30 days of admission, patients with moderately dependent craniocerebral disorders and dyskinesia frequently experienced falls during typical daytime shifts in areas characterized by endemic conditions.Keywords: daily living activities, dyskinesia, fall, hospitalized patients, rehabilitation department, retrospective analysis

Ding-Yun Feng,* Jian-Xia Zhou,* Xia Li, Wen-Bin Wu, Yu-Qi Zhou, Tian-Tuo Zhang Department of Pulmonary and Critical Care Medicine, Third Affiliated Hospital of Sun Yat-Sen University, Institute of Respiratory Diseases of Sun Yat-Sen University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tian-Tuo Zhang, Department of Pulmonary and Critical Care Medicine, Third Affiliated Hospital of Sun Yat-sen University, Institute of Respiratory Diseases of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, People’s Republic of China, Tel +86-20-85252241, Fax +86-20-85253084, Email zhtituli@163.comPurpose: Acinetobacter baumannii is the most common microorganism in sputum cultures from long-term hospitalized patients and is often the cause of hospital-acquired pneumonia (HAP), which is usually associated with poor prognosis and high mortality. It is sometimes difficult to distinguish between A. baumannii infection and colonization. This study aimed to evaluate factors that differentiate infection from colonization and predict mortality in patients with nosocomial pneumonia caused by A. baumannii.Patients and Methods: The data used in this study were collected in our hospital between January 2018 and December 2020 from patients whose sputum cultures were positive for A. baumannii.Results: A total of 714 patients were included, with 571 in the infection group and 143 in the colonization group. The in-hospital mortality rate in the infection group was 20.5%. Univariate and multivariate logistic regression analyses showed that age, total number of inpatient departments, absolute neutrophil count, and C-reactive protein (CRP) level helped distinguish between infection and colonization. The area under the receiver operating characteristic curve (ROC) of the identification model was 0.694. In the infection group, age, Charlson comorbidity score, neutrophil-to-lymphocyte ratio, blood urea nitrogen/albumin ratio, CRP level, presence of multidrug resistance, and clinical pulmonary infection score (≥ 6) ratio were associated with in-hospital mortality. The area under the ROC curve for the prediction model was 0.828. The top three drug resistance rates in the infection group were 100% (cefazolin), 98.77% (ceftriaxone), and 71.8% (cefuroxime).Conclusion: The combination of common parameters helps identify A. baumannii respiratory tract infection or colonization. Several novel predictors can be used to predict the risk of death from A. baumannii pneumonia to reduce mortality. The drug resistance of A. baumannii remains high.Keywords: Acinetobacter baumannii, infection, colonization, mortality, drug resistance

Jian xin Zhou,1,* Li jin Feng,2,* Xi Zhang3 1Department of Gynecology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, 2Department of Pathology, Shanghai Tenth People’s Hospital, Tongji University, School of Medicine, Shanghai, 3Department of Radiation Oncology, Affiliated Hospital of Hebei University, Baoding, China *These authors contributed equally to this work Purpose: Hematologic toxicities, including neutropenia, thrombocytopenia, and anemia, are major adverse effects of PARP inhibitors (PARPis), but the incidence rate and overall risk has not been systematically studied. Therefore, we conducted a meta-analysis of published clinical trials to investigate the incidence and relative risks (RRs) of severe (high-grade) hematologic events in cancer patients treated with PARPis.Methods: PubMed, Embase, and oncology conference proceedings were searched for relevant studies. Eligible studies were Phase II and III randomized controlled trials (RCTs) of PARPis in cancer patients with adequate safety data on hematologic toxicities. The summary incidence, RRs, and 95% confidence intervals (CIs) were calculated.Results: A total of 2,479 patients from 12 RCTs revealed that the incidence of PARPi-associated severe hematologic toxicities was, respectively: neutropenia: 32.9% (95% CI, 20.5%–48.3%); thrombocytopenia: 15.9% (95% CI, 9.5%–25.4%), and anemia: 9.1% (95% CI, 5.1%–15.7%). Olaparib was associated with an increased risk of severe neutropenia. Veliparib was associated with an increased risk of severe neutropenia and thrombocytopenia. Niraparib was associated with an increased risk of severe thrombocytopenia, anemia, and neutropenia. When stratified by combination therapy, significantly increased risk of hematologic toxicities was observed for patients treated with PARPis monotherapy and PARPis combined with single-agent chemotherapy.Conclusion: Treatment with PARPis olaparib, veliparib, and niraparib is associated with a significant increase in the risk of hematologic toxicities in cancer patients, and frequent clinical monitoring should be emphasized when managing these PARPis. Keywords: hematologic toxicities, PARP inhibitors, cancer, meta-analysis, RCTs

Guang-Hua Xiang,1,2,* Guo-Bin Hong,2,3,* Yong Wang,2 Du Cheng,2 Jing-Xing Zhou,1 Xin-Tao Shuai21Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China; 2PCFM Laboratory of Ministry of Education, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, People's Republic of China; 3Department of Radiology, Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, People's Republic of China*These two authors contributed equally to this workObjective: To evaluate the cytotoxicity of poly(ethylene glycol)-block-poly(D,L-lactic acid) (PEG-PDLLA) nanovesicles loaded with doxorubicin (DOX) and the photosensitizer hematoporphyrin monomethyl ether (HMME) on human hepatocellular carcinoma HepG2 cells and to investigate potential apoptotic mechanisms.Methods: PEG-PDLLA nanovesicles were simultaneously loaded with DOX and HMME (PEG-PDLLA-DOX-HMME), and PEG-PDLLA nanovesicles were loaded with DOX (PEG-PDLLA-DOX), HMME (PEG-PDLLA-HMME), or the PEG-PDLLA nanovesicle alone as controls. The cytotoxicity of PEG-PDLLA-DOX-HMME, PEG-PDLLA-DOX, PEG-PDLLA-HMME, and PEG-PDLLA against HepG2 cells was measured, and the cellular reactive oxygen species, percentage of cells with mitochondrial membrane potential depolarization, and apoptotic rate following treatment were determined.Results: Four nanovesicles (PEG-PDLLA-DOX-HMME, PEG-PDLLA-DOX, PEG-PDLLA-HMME, and PEG-PDLLA) were synthesized, and mean particle sizes were 175±18 nm, 154±3 nm, 196±2 nm, and 147±15 nm, respectively. PEG-PDLLA-DOX-HMME was more cytotoxic than PEG-PDLLA-DOX, PEG-PDLLA-HMME, and PEG-PDLLA. PEG-PDLLA-HMME-treated cells had the highest mean fluorescence intensity, followed by PEG-PDLLA-DOX-HMME-treated cells, whereas PEG-PDLLA-DOX- and PEG-PDLLA-treated cells had a similar fluorescence intensity. Mitochondrial membrane potential depolarization was observed in 54.2%, 59.4%, 13.8%, and 14.8% of the cells treated with PEG-PDLLA-DOX-HMME, PEG-PDLLA-HMME, PEG-PDLLA-DOX, and PEG-PDLLA, respectively. The apoptotic rate was significantly higher in PEG-PDLLA-DOX-HMME-treated cells compared with PEG-PDLLA-DOX- and PEG-PDLLA-HMME-treated cells.Conclusion: The PEG-PDLLA nanovesicle, a drug delivery carrier, can be simultaneously loaded with two anticancer drugs (hydrophilic DOX and hydrophobic HMME). PEG-PDLLA-DOX-HMME cytotoxicity to HepG2 cells is significantly higher than the PEG-PDLLA nanovesicle loaded with DOX or HMME alone, and DOX and HMME have a synergistic effect against human hepatocellular carcinoma HepG2 cells.Keywords: polymeric vesicles, hematoporphyrin monomethyl ether, HMME, photodynamic therapy, PDT

Guo-bin Hong,1,2 Jing-xing Zhou,2 Ren-xu Yuan31Department of Radiology, Fifth Affiliated Hospital, Zhuhai, 2Department of Radiology, Sun Yat-sen Memorial Hospital, Guangzhou, 3School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, ChinaAbstract: Targeted delivery of contrast agents is a highly desirable strategy for enhancing diagnostic efficiency and reducing side effects and toxicity. Water-soluble and tumor-targeting superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized by loading hydrophobic SPIONs into micelles assembled from an amphiphilic block copolymer poly(ethylene glycol)-poly(ε-caprolactone) (PEG-PCL) bearing folate in the distal ends of PEG chains. Compared to the water-soluble SPIONs obtained by small molecular surfactant coating, ultrasmall SPION encapsulation with PEG-PCL micelles (PEG-PCL-SPIONs) simultaneously increases transverse (r2) and decreases longitudinal (r1) magnetic resonance (MR) relaxivities of water proton in micelle solution, leading to a notably high r2/r1 ratio up to 78, which makes the PEG-PCL-SPIONs a highly sensitive MR imaging (MRI) T2 contrast agent. The mean size of folate-attached SPION micelles (Fa-PEG-PCL-SPIONs) is 44 ± 3 nm on average, ideal for in vivo MRI applications in which long circulation is greatly determined by small particle size and is highly desirable. Prussian blue staining of BEL-7402 cells over-expressing folate receptors, after incubation with micelle-containing medium, demonstrated that folate functionalization of the magnetic particles significantly enhanced their cell uptake. The potential of Fa-PEG-PCL-SPIONs as a potent MRI probe for in vivo tumor detection was assessed. At 3 hours after intravenous injection of the Fa-PEG-PCL-SPION solution into mice bearing subcutaneous xenografts of human BEL-7402 hepatoma, a 41.2% signal intensity decrease was detected in the T2-weighted MR images of the tumor, indicating the efficient accumulation of Fa-PEG-PCL-SPIONs in the tumor tissue.Keywords: tumor targeting, magnetic resonance imaging, polymeric micelles, superparamagnetic iron oxide

Objective: The objective of this study was to compare the effects of two kinds of gargles (Koushu & Koutai) on oral mucositis (OM) in patients with agranulocytosis., Methods: One hundred eighty patients who underwent allogeneic hematopoietic stem cell transplantation in the Peking University Institute of Hematology were enrolled from March 2018 to January 2019. The subjects were randomly divided into two groups by random number table. The observation group gargled with Koushu gargle, whereas the control group gargled with Koutai gargle. Patients in both groups used 10 to 15 mL of gargles for 2 minutes when awake in the morning, 30 minutes after each meal, and before sleep. The two groups used the same way to gargle except the types of gargle used. The difference of incidence, grade, healing time, and pain grade of oral mucositis were analyzed., Results: The incidence of oral mucositis in the observation group was significantly lower than that in the control group (P < .01).There were no significant difference in grade of OM, healing time, or pain grade between the two groups (P > .05). The effect of the Koushu gargle on the prevention of OM among the patients with agranulocytosis is better than that of the Koutai gargle. The Koushu gargle is better suited than the Koutai gargle as a prevention and treatment option for the patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Gallbladder cancer (GBC) was once considered a contraindication for laparoscopic surgery, but it is becoming more common to use laparoscopic surgery for GBC treatment. The aim of this study was to analyze the long- and short-term outcomes of patients with more advanced T-staged GBC treated with curative intent as defined by the National Comprehensive Cancer Network (NCCN) after laparoscopic resection (LR) versus open resection (OR)., Methods: A multicenter database was used to select consecutive GBC patients treated with curative-intent resection as defined by the NCCN between 2016 and 2020. The patients were divided into the LR group and the OR group. Propensity score matching (PSM) was used to eliminate selection bias. The endpoints were overall survival (OS), progression-free survival (PFS), and short-term outcomes. Risk factors that were independently associated with OS and PFS were identified., Results: Of 626 GBC patients treated with curative-intent resection, after PSM, 51 patients were in the LR group and 153 patients were in the OR group. The LR group had more patients who were suitable to receive adjuvant chemotherapy (AC), a longer operation time, more harvested lymph nodes, and a lower overall morbidity rate. The rates of OS and PFS were not significantly different between the two groups. AC was independently associated with better OS and PFS., Conclusions: The overall morbidity of GBC patients after LR was lower, but the long-term outcomes between LR and OR were not significantly different. The GBC patients treated with LR were more likely to receive AC, and the use of AC after curative-intent resection of GBC helped achieve better long-term survival outcomes., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-23-518/coif). W.Y.L. serves as an unpaid editorial board member of Hepatobiliary Surgery and Nutrition. The other authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

There are enormous differences in benzo[a]pyrene (BaP) acute toxicity tests on Daphnia magna , according to previous publications. The explanations of the reasons for this extreme variation are necessary. In this context, the acute toxicity tests of different experiment conditions (light/dark, culture medium, and solvent) were conducted on Daphnia magna with BaP as the toxicant of concern. Based on the experiments above, molecular dynamics (MD) simulations were employed to investigate the mechanisms of action. According to our results, the significant influence of light exposure on the acute toxicity test of BaP ( p < 0.05) on D. magna was recorded. On the basis of the MD simulations, it was possible that BaP may not affect the normal operation of Superoxide Dismutase and Catalase directly, and it could be quickly transferred from the body through Glutathione S-transferase and Cytochromes P450. Therefore, when exposed to light, the oxidative stress process intensifies, causing damage to Daphnia magna . Apparently, the ecotoxicity tests based on inhibition for D. magna cannot adequately reflect the toxic effects of BaP.

Background: Acute respiratory distress syndrome (ARDS) is a severe condition characterized by lung stiffness and compromised gas exchange, often requiring mechanical ventilation for treatment. In addition to its clinical significance, understanding the publication trends and research patterns in respiratory mechanics related to ARDS can provide insights into the evolution of this field from a bibliometric perspective, aiding in strategic planning and resource allocation for future research endeavors., Objective: This study aimed to explore the trends and identify the hotspots in respiratory mechanics research related to ARDS., Methods: All relevant studies on respiratory mechanics of ARDS published between 1985 and 2023 were retrieved from the Web of Science Core Collection (WoSCC), and the retrieval strategy was topic search "TS = respiratory mechanics OR lung mechanics AND TS = ARDS OR acute respiratory distress syndrome." Annual trends, citation patterns, and contributions from countries, institutions, authors, and journals were analyzed using Bibliometrix Biblioshiny. Networks and overlay of authors, institutions, countries, journals, co-citations, and keywords were analyzed and visualized using VOSviewer., Results: Our analysis included 1,248 articles published between 1985 and 2023, revealing fluctuations in publication output over time. The United States emerged as the leading contributor, with Critical Care Medicine being the most prominent journal. Key research themes included mechanical ventilation, acute lung injury, and protective ventilation strategies. International collaboration was evident, facilitating knowledge exchange and interdisciplinary cooperation., Conclusion: Our study sheds light on the evolving landscape of respiratory mechanics research in ARDS. International collaboration is pivotal in advancing the field, while researchers increasingly focus on personalized approaches to address the complexities of ARDS respiratory mechanics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhou, Tian, Wang, Wang, Yang, Zhou and Zhang.)

Inflammation is a potential risk factor of voriconazole (VCZ) overdose, procalcitonin (PCT) is reported to act as a diagnostic marker for bacterial infections. However, the association of PCT with VCZ trough serum concentrations (VCZ-C min ) is not fully clear. Our study aims to investigate the associations between PCT and VCZ-C min . In this retrospective cohort study, we collected the clinical data of 147 patients who received VCZ and monitored the VCZ concentration of them in our hospital from August 2017 to August 2021. All patients underwent routine clinical examinations on the day or the day before VCZ administration. General information and clinical symptoms of these patients were recorded. Multivariate liner analysis showed that PCT was significantly associated with VCZ-C min (p < 0.001). Overall, it was shown that VCZ-C min was significantly increased by 0.32 µg/mL for each fold increment in PCT in crude model. In the minor adjusted model (Model 1, adjustment for sex, age, albumin, direct bi1irubin, WBC) and fully adjusted model (Model 2, adjustment for sex, age, albumin, direct bilirubin, WBC, AST and ALT), VCZ-C min was significantly increased by 0.23 µg/mL and 0.21 µg/mL, respectively, for each fold increment in PCT. In conclusion, this research reveals the correlation between PCT and VCZ-C min , indicating that PCT has the potential to serve as a valuable biomarker for drug monitoring in the treatment of VCZ., (© 2024. The Author(s).)

The low-order normal modes with small grazing angles (SGA) often control long-range sound field characteristics in shallow water. The SGA reflection loss from a half-space low-velocity bottom (LVB) is independent of the sound attenuation, except around the angle of complete transmission; the SGA bottom reflection loss (BRL) from a seafloor with a top low-velocity layer is very insensitive to the LVB attenuation also, except around a few selected frequencies. Thus, the "seafloor velocity-attenuation coupling" problem will be more fatal for LVB geo-acoustic inversions. The dispersion equation of the normal modes in the LVB layer is coincidentally the same as the singularity expression of the SGA reflection coefficient in the water column, resulting in a sound siphon effect that causes the abnormally high SGA BRL and transmission loss in the water at the siphon frequencies. The siphon effect is very sensitive to seafloor acoustic parameters, might offer a physical base for geo-acoustic inversion, and show a dim light in a "gray area" for inverting the LVB sound attenuation at low to mid frequencies. As an example, the acoustic siphon effect and related seafloor geophysical parameters forming it in the Yellow Sea are reported in this paper., (© 2024 Acoustical Society of America.)

Aims: Despite islet transplantation has proved a great potential to become the standard therapy for type 1 diabetes mellitus (T1DM), this approach remains limited by ischemia, hypoxia, and poor revascularization in early post-transplant period as well as inflammation and life-long host immune rejection. Here, we investigate the potential and mechanism of human amniotic mesenchymal stem cells (hAMSCs)-islet organoid to improve the efficiency of islet engraftment in immunocompetent T1DM mice., Main Methods: We generated the hAMSC-islet organoid structure through culturing the mixture of hAMSCs and islets on 3-dimensional-agarose microwells. Flow cytometry, whole-body fluorescent imaging, immunofluorescence, Calcein-AM/PI staining, ELISA, and qPCR were used to assess the potential and mechanism of shielding hAMSCs to improve the efficiency of islet transplantation., Key Findings: Transplant of hAMSC-islet organoids results in remarkably better glycemic control, an enhanced glucose tolerance, and a higher β cell mass in vivo compared with control islets. Our results show that hAMSCs shielding provides an immune privileged microenvironment for islets and promotes graft revascularization in vivo. In addition, hAMSC-islet organoids show higher viability and reduced dysfunction after exposure to hypoxia and inflammatory cytokines in vitro. Finally, our results show that shielding with hAMSCs leads to the activation of PKA-CREB-IRS2-PI3K and PKA-PDX1 signaling pathways, up-regulation of SIL1 mRNA levels, and down-regulation of MT1 mRNA levels in β cells, which ultimately promotes the synthesis, folding and secretion of insulin, respectively., Significance: hAMSC-islet organoids can evidently increase the efficiency of islet engraftment and might develop into a promising alternative for the clinical treatment of T1DM., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Although pressure support ventilation is one of the most commonly used assisted ventilation modes in intensive care units, there is still a lack of precise strategies for setting pressure support. By performing an end-inspiratory airway occlusion, the difference between the peak and plateau airway pressure, which is defined as pressure muscle index (PMI), can be easily measured on the ventilator screen. Previous studies have shown that PMI is accurate in detecting high and low inspiratory effort. No study has been conducted to investigate the use of PMI as an indicator for setting inspiratory pressure support., Method and Analysis: This is a study protocol for a prospective, single-centre, randomised controlled, pilot trial. Sixty participants undergoing pressure support ventilation will be randomly assigned in a 1:1 ratio to the control group or intervention group, with pressure support adjusted according to standard care or guided by the PMI strategy for 48 hours, respectively. The feasibility of the PMI-guided strategy will be evaluated. The primary endpoint is the proportion of inspiratory effort measurements within a well-accepted 'normal' range, which is predefined as oesophageal pressure-time product per minute between 50 and 200 cmH 2 O⋅s/min, for each patient during 48 hours of pressure support adjustment., Ethics and Dissemination: The study protocol has been approved by Beijing Tiantan Hospital (KY2023-005-02). The data generated in the present study will be available from the corresponding author on reasonable request. The results of the trial will be submitted to international peer-reviewed journals., Trial Registration Number: NCT05963737; ClinicalTrials.org., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The recycling and utilization of precious metals have emerged as a critical research focus in advancing the development of the circular economy. Among numerous methods for recovering precious metals such as gold, adsorbents with both high adsorption selectivity and capacity have become key technologies. This article incorporated the N-phenylpyrrolidine into a flexible porous polynorbornene backbone to create a class of distinctive porous organic polymers, named BIT-POP-14-BIT-POP-17. Through a reductive capture mechanism, the reductive adsorption sites of N-phenylpyrrolidine coordinate selectively with precious metals, the reduced metal is captured by the hierarchically porous polymers with flexible backbone. This approach leads to remarkable gold recovery efficiency, achieving a record of 2321 mg g -1 at ambient conditions, and 3020 mg g -1 under UV light, surpassing the theoretical limit. The porous polymers are filled in a column for a continuous uptake of gold from waste printed circuit boards (PCBs), showing recovery efficiency toward gold as high as 95% after 84 h. Overall, this work offers a new perspective on designing novel adsorbents for precious metal recovery, providing inspiration for researchers to explore novel adsorption modes and contribute to the advancement of the circular economy., (© 2024 Wiley‐VCH GmbH.)

Alteration of DNA methylation leads to diverse diseases, and the dynamic changes of DNA methylation (DNAm) on sets of CpG dinucleotides in mammalian genomes are termed "DNAm age" and "epigenetic clocks" that can predict chronological age. However, whether and how dysregulation of DNA methylation promotes cyst progression and epigenetic age acceleration in autosomal dominant polycystic kidney disease (ADPKD) remains elusive. Here, we show that DNA methyltransferase 1 (DNMT1) is upregulated in cystic kidney epithelial cells and tissues and that knockout of Dnmt1 and targeting DNMT1 with hydralazine, a safe demethylating agent, delays cyst growth in Pkd1 mutant kidneys and extends life span of Pkd1 conditional knockout mice. With methyl-CpG binding domain (MBD) protein-enriched genome sequencing (MBD-seq), DNMT1 chromatin immunoprecipitation (ChIP)-sequencing and RNA-sequencing analysis, we identified two novel DNMT1 targets, PTPRM and PTPN22 (members of the protein tyrosine phosphatase family). PTPRM and PTPN22 function as mediators of DNMT1 and the phosphorylation and activation of PKD-associated signaling pathways, including ERK, mTOR and STAT3. With whole-genome bisulfide sequencing in kidneys of patients with ADPKD versus normal individuals, we found that the methylation of epigenetic clock-associated genes was dysregulated, supporting that epigenetic age is accelerated in the kidneys of patients with ADPKD. Furthermore, five epigenetic clock-associated genes, including Hsd17b14, Itpkb, Mbnl1, Rassf5 and Plk2, were identified. Thus, the diverse biological roles of these five genes suggest that their methylation status may not only predict epigenetic age acceleration but also contribute to disease progression in ADPKD., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Lipid accumulation and redox imbalance, resulting from dysregulation of hepatic fatty acids oxidation, contribute to the development of steatohepatitis and insulin resistance. Recently, dysregulated RNA N 6 -methyladenosine (m 6 A) methylation modification has been found involving fatty liver. However, the role of methyltransferase-like 14 (METTL14), the core component of m 6 A methylation, in the development of steatohepatitis is unknown. Herein, we aimed to explore the role of METTL14 on steatohepatitis and insulin resistance in mice with metabolic dysfunction-associated steatotic liver disease (MASLD)., Methods: The liver tissues of mice and patients with MASLD were collected to detect the expression of METTL14. METTL14 overexpression and METTL14 silence were used to investigate the effect of METTL14 on lipid metabolism disorder in vivo and in vitro . Knockout of METTL14 in primary hepatocytes was used to investigate the role of Sirtuin 1 (SIRT1) on lipid accumulation induced by METTL14., Results: METTL14 was dramatically up-regulated in the livers of db/db mice, high-fat diet (HFD)-fed mice, and patients with MASLD. METTL14 overexpression exacerbated MASLD and promoted lipid metabolism disorder and insulin resistance in mice. Conversely, METTL14 knockout ameliorated lipid deposition and insulin resistance in HFD-fed mice. Furthermore, METTL14 overexpression facilitated lipid accumulation, while METTL14 knockout reduced lipid accumulation in HepG2 cells and primary hepatocytes. In addition, METTL14 lost up-regulated SIRT1 expression in hepatocytes. SIRT1 deficiency abrogated the ameliorating effects of METTL14 downregulation in MASLD mice., Conclusions: These findings suggest that dysfunction of the METTL14-SIRT1 pathway might promote hepatic steatosis and insulin resistance., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective: To describe the epidemiology of injuries and illnesses sustained during the Beijing 2022 Paralympic Winter Games, organised in a closed-loop environment to adhere with COVID-19 restrictions., Methods: Injuries and illnesses from all teams were recorded on a daily basis by team medical staff on a web-based form and by local organising committee medical (polyclinic) facilities and venue medical support. Duplicates recorded on both systems were removed. Incidence of injuries and illnesses are reported per 1000 athlete days (95% CI)., Results: 564 athletes (426 male and 138 female) representing 46 countries were monitored for the 13-day period of the Beijing 2022 Paralympic Winter Games (7332 athlete days). The overall incidences were 13.0 injuries (10.6-15.8) and 6.1 illnesses (4.5-8.4) per 1000 athlete days. The incidence of injury in alpine skiing (19.9; 15.2-26.1) was significantly higher compared with Nordic skiing, ice hockey and wheelchair curling (p<0.05), while the incidence of respiratory illness was significantly higher in Nordic skiing (1.6; 0.9-2.9) compared with alpine skiing, ice hockey and snowboarding (p<0.05)., Conclusion: The incidence of both injury and illness at the Beijing 2022 Games were the lowest yet reported in the Paralympic Winter Games. The incidence of injury was highest in alpine skiing. These findings underscore the importance of ongoing vigilance and continued injury risk mitigation strategies to safeguard the well-being of athletes in these high-risk competitions. Respiratory illnesses were most commonly reported in Nordic skiing, which included the three cases of COVID-19 recorded at the games., Competing Interests: Competing interests: WD and MS are associate editors of BJSM IPHP editions., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Chlorinated polyfluorinated ether sulfonate, commercially known as F-53B, has been associated with adverse birth outcomes. However, the reproductive toxicology of F-53B on the placenta remains poorly understood. To address this gap, we examined the impact of F-53B on placental injury and its underlying molecular mechanisms in vivo. Pregnant C57BL/6 J female mice were randomly allocated to three groups: the control group, F-53B 0.8 µg/kg/day group, and F-53B 8 µg/kg/day group. After F-53B exposure through free drinking water from gestational day (GD) 0.5-14.5, the F-53B 8 µg/kg/day group exhibited significant increases in placental weights and distinctive histopathological alterations, including inflammatory cell infiltration, heightened syncytiotrophoblast knots, and a loosened trophoblastic basement membrane. Within the F-53B 8 µg/kg/day group, placental tissue exhibited increased apoptosis, as indicated by increased caspase3 activation. Furthermore, F-53B potentially induced the NF-κB signaling pathway activation through IκB-α phosphorylation. Subsequently, this activation upregulated the expression of inflammatory cytokines and components of the NLRP3 inflammasome, including activated caspase1, IL-1β, IL-18, and cleaved gasdermin D (GSDMD), ultimately leading to pyroptosis in the mouse placenta. Our findings reveal a pronounced inflammatory injury in the placenta due to F-53B exposure, suggesting potential reproductive toxicity at concentrations relevant to the human population. Further toxicological and epidemiological investigations are warranted to conclusively assess the reproductive health risks posed by F-53B., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The prognostic value of carbohydrate antigen 19-9 (CA19-9) is known to be affected by elevated bilirubin levels in patients with gallbladder carcinoma (GBC). The clinical significance of changes in the ratio of CA19-9 levels to total bilirubin (TB) levels in patients with GBC after curative-intent resection remains unknown. The aim of this study was to determine the prognostic value of changes in preoperative and postoperative CA19-9/TB ratio in these patients., Methods: Prospectively collected data on consecutive patients who underwent curative-intent resection for GBC between January 2015 and December 2020 stored in a multicenter database from 10 hospitals were analyzed in this retrospective cohort study. Based on the adjusted CA19-9 defined as the ratio of CA19-9 to TB, and using 2×10 3  U/µmol as the upper normal value, patients were divided into a normal group (with normal preoperative and postoperative adjusted CA19-9), a normalization group (with abnormal preoperative but normal postoperative adjusted CA19-9), and a non-normalization group (with abnormal postoperative adjusted CA19-9). The primary outcomes were overall survival (OS) and recurrence-free survival (RFS). The log-rank test was used to compare OS and RFS among the groups. The Cox regression model was used to determine factors independently associated with OS and RFS., Results: The normal group ( n =179 patients) and the normalization group ( n =73 patients) had better OS and RFS than the non-normalization group ( n =65 patients) (the 3-year OS rates 72.0%, 58.4% and 24.2%, respectively; the RFS rates 54.5%, 25.5% and 11.8%, respectively; both P <0.001). There were no significant differences between the normal and the normalization groups in OS and RFS (OS, P =0.255; RFS, P =0.130). Cox regression analysis confirmed that the non-normalization group was independently associated with worse OS and RFS. Subgroup analysis revealed that the non-normalization group of patients who received adjuvant therapy had significantly improved OS and RFS as compared to those who did not receive adjuvant therapy (OS, P =0.025; RFS, P =0.003)., Conclusions: Patients with GBC who underwent curative-intent surgical resection with postoperative abnormal levels of adjusted CA19-9 (the CA19-9/TB ratio) were associated with poorer long-term survival outcomes. Adjuvant therapy after surgery improved the long-term outcomes of these patients., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Fibroblasts are ubiquitous mesenchymal cells that exhibit considerable molecular and functional heterogeneity. Besides maintaining stromal integrity, oral fibroblast subsets are thought to play an important role in host-microbe interaction during injury repair, which is not well explored in vivo. Here, we characterize a subset of fibroblast lineage labeled by paired-related homeobox-1 promoter activity (Prx1Cre + ) in oral mucosa and skin and demonstrate these fibroblasts readily respond to microbial products to facilitate the normal wound healing process. Using a reporter mouse model, we determined that Prx1Cre + fibroblasts had significantly higher expression of toll-like receptors 2 and 4 compared to other fibroblast populations. In addition, Prx1 immunopositive cells exhibited heightened activation of inflammatory transcription factor NF-κB during the early wound healing process. At the cytokine level, CXCL1 and CCL2 were significantly upregulated by Prx1Cre + fibroblasts at baseline and upon LPS stimulation. Importantly, lineage-specific knockout to prevent NF-κB activation in Prx1Cre + fibroblasts drastically impaired both oral and skin wound healing processes, which was linked to reduced macrophage infiltration, failure to resolve inflammation, and clearance of bacteria. Together, our data implicate a pro-healing role of Prx1-lineage fibroblasts by facilitating early macrophage recruitment and bacterial clearance., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Timely palliative care and surgical interventions improve symptoms, health-related quality of life (HRQoL), and reduce medical cost for seriously ill adults at end of life (EOL). However, there is still poor delivery and underutilization of these palliative services. We hypothesize that the sub-optimal delivery is due to limited understanding among healthcare providers., Methods: A nationwide cross-sectional online survey was conducted among primary and tertiary healthcare providers. The survey assessed challenges faced, palliative education, confidence in managing palliative patients, and knowledge on palliative surgery. Overall palliative care awareness and knowledge was assessed using a 6-point score. Likelihood of considering various palliative interventions at EOL was also determined using a threshold score (higher score = higher threshold)., Results: There were 145 healthcare providers who completed the survey (81.9% response rate); majority reported significant challenges in providing various aspects of palliative care: 57% ( n = 82) in the provision of emotional support. Sixty-nine percent ( n = 97) in managing social issues, and 71% ( n = 103) in managing family expectations. Most expressed inadequate palliative care training in both under-graduate and post-graduate training and lack confidence in managing EOL issues. Up to 57% had misconceptions regarding potential benefits, morbidity and mortality after palliative surgery. In general, most providers had high thresholds for Intensive Care Unit admissions and palliative surgery, and were more likely to recommend endoscopic or interventional radiology procedures at EOL., Conclusion: Healthcare providers in Singapore have poor knowledge and misconceptions about palliative care and surgery. Improving awareness and education among those caring for seriously ill adults is essential., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Juan, Ng, Wong, Fong, Lee, Lie, Zhou, Cai, Ong, Seo, Chia and Wong.)

The primary cilium is a microtubule-based sensory organelle that plays a critical role in signaling pathways and cell cycle progression. Defects in the structure and/or function of the primary cilium result in developmental diseases collectively known as ciliopathies. However, the constituents and regulatory mechanisms of the primary cilium are not fully understood. In recent years, the activity of the epigenetic modifier SMYD3 has been shown to play a key role in the regulation of cell cycle progression. However, whether SMYD3, a histone/lysine methyltransferase, contributes to the regulation of ciliogenesis remains unknown. Here, we report that SMYD3 drives ciliogenesis via the direct and indirect regulation of cilia-associated components. We show that SMYD3 is a novel component of the distal appendage and is required for centriolar appendage assembly. The loss of SMYD3 decreased the percentage of ciliated cells and resulted in the formation of stumpy cilia. We demonstrated that SMYD3 modulated the recruitment of centrosome proteins (Cep164, Fbf1, Ninein, Ttbk2 and Cp110) and the trafficking of intraflagellar transport proteins (Ift54 and Ift140) important for cilia formation and maintenance, respectively. In addition, we showed that SMYD3 regulated the transcription of cilia genes and bound to the promoter regions of C2cd3, Cep164, Ttbk2, Dync2h1 and Cp110. This study provides insights into the role of SMYD3 in cilia biology and suggests that SMYD3-mediated cilia formation/function may be relevant for cilia-dependent signaling in ciliopathies.

The improved wear and corrosion resistance of gray cast iron (GCI) with enhanced mechanical properties is a proven stepping stone towards the longevity of its versatile industrial applications. In this article, we have tailored the microstructural properties of GCI by alloying it with titanium (Ti) and tungsten (W) additives, which resulted in improved mechanical, wear, and corrosion resistance. The results also show the nucleation of the B-, D-, and E-type graphite flakes with the A-type graphite flake in the alloyed GCI microstructure. Additionally, the alloyed microstructure demonstrated that the ratio of the pearlite volume percentage to the ferrite volume percentage was improved from 67/33 to 87/13, whereas a reduction in the maximum graphite length and average grain size from 356 ± 31 µm to 297 ± 16 µm and 378 ± 18 µm to 349 ± 19 µm was detected. Consequently, it improved the mechanical properties and wear and corrosion resistance of alloyed GCI. A significant improvement in Brinell hardness, yield strength, and tensile strength of the modified microstructure from 213 ± 7 BHN to 272 ± 8 BHN, 260 ± 3 MPa to 310 ± 2 MPa, and 346 ± 12 MPa to 375 ± 7 MPa was achieved, respectively. The substantial reduction in the wear rate of alloyed GCI from 8.49 × 10 -3 mm 3 /N.m to 1.59 × 10 -3 mm 3 /N.m resulted in the upgradation of the surface roughness quality from 297.625 nm to 192.553 nm. Due to the increase in the corrosion potential from -0.5832 V to -0.4813 V, the impedance of the alloyed GCI was increased from 1545 Ohm·cm 2 to 2290 Ohm·cm 2 . On the basis of the achieved experimental results, it is suggested that the reliability of alloyed GCI based on experimentally validated microstructural compositions can be ensured during the operation of plants and components in a severe wear and corrosive environment. It can be predicted that the proposed alloyed GCI components are capable of preventing the premature failure of high-tech components susceptible to a wear and corrosion environment.

Attenuation is the most difficult seafloor acoustic property to get, particularly at low to mid frequencies. For low velocity bottoms (LVB), it becomes even more challenging, due to its small attenuation and lower velocity (relative to the velocity of the adjacent water). The latter one causes a fatal "seafloor velocity-attenuation couplings" in geo-acoustic inversions. Thus, attenuation inversions for the LVB require an accurate seafloor velocity profile, especially the velocity in the LVB layer. The propagation of explosive sound in the Yellow Sea with a strong thermocline and a top LVB layer exhibits many prominent characteristics: modal dispersion (the ground wave, water wave, Airy phase), two groups of water waves at high frequencies, and the siphon effect which causes abnormally large sound transmission loss at selected frequencies, etc. These observations are used to precisely measure the critical frequency, the Airy frequency, Airy wave velocity, 1st mode group velocity, and to derive the velocities in the LVB layer and in the basement. Using inverted seafloor parameters, the source level-normalized transmission loss and the first mode decay rate in ranges up to 27.66 km, the sound attenuations in the LVB are derived for a frequency range of 13-5000 Hz., (© 2024 Acoustical Society of America.)

Aim: To evaluate the effect of aging on pulmonary vessels based on computed tomography (CT) quantification and analyse the correlation between quantitative pulmonary vascular volume and pulmonary function during aging., Materials and Methods: A total of 330 healthy adult volunteers, including 161 men (53 aged 20-39 years, 61 aged 40-59 years, and 47 aged ≥60 years) and 169 women (53 aged 20-39 years, 63 aged 40-59 years, and 53 aged ≥60 years) were recruited in this study. AVIEW software was used to quantitatively measure pulmonary vascular volume, including pulmonary total blood vessel volume (TBV) and small blood vessel volume with a cross-sectional area of <5 mm 2 (BV5). Pulmonary vascular volume parameters were standardised using the ratio of vascular volume to the body surface area (BSA; TBV/BSA and BV5/BSA). Subsequently, the effect of aging on the pulmonary vessels was analysed., Results: The pulmonary vascular volume parameters TBV/BSA and BV5/BSA of the whole lung, right lung, and left lung decreased significantly with increasing age (p<0.05). Additionally, TBV/BSA and BV5/BSA of the whole lung were higher in men than in women. The declining trend of pulmonary vascular volume was consistent in men and women and increased with age., Conclusions: The pulmonary vascular volume parameters, TBV/BSA and BV5/BSA, decreased with age and were weakly positively correlated with pulmonary function., (Copyright © 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: The authors declare no conflict of interest.

Background: The successful implementation of assisted ventilation depends on matching the patient's effort with the ventilator support. Pressure muscle index (PMI), an airway pressure based measurement, has been used as noninvasive monitoring to assess the patient's inspiratory effort. The authors aimed to evaluate the feasibility of pressure support adjustment according to the PMI target and the diagnostic performance of PMI to predict the contribution of the patient's effort during ventilator support., Methods: In this prospective physiological study, 22 adult patients undergoing pressure support ventilation were enrolled. After an end-inspiratory airway occlusion, airway pressure reached a plateau, and the magnitude of change in plateau from peak airway pressure was defined as PMI. Pressure support was adjusted to obtain the PMI which was closest to -1, 0, +1, +2, and + 3 cm H 2 O. Each pressure support level was maintained for 20 min. Esophageal pressure was monitored. Pressure-time products of respiratory muscle and ventilator insufflation were measured, and the fraction of pressure generated by the patient was calculated to represent the contribution of the patient's inspiratory effort., Results: A total of 105 datasets were collected at different PMI-targeted pressure support levels. The differences in PMI between the target and the obtained value were all within ±1 cm H 2 O. As targeted PMI increased, pressure support settings decreased significantly from a median (interquartile range) of 11 (10-12) to 5 (4-6) cm H 2 O ( p  < 0.001), which resulted in a significant increase in pressure-time products of respiratory muscle [from 2.9 (2.1-5.0) to 6.8 (5.3-8.1) cm H 2 O•s] and the fraction of pressure generated by the patient [from 25% (19-31%) to 72% (62-87%)] ( p  < 0.001). The area under receiver operating characteristic curves for PMI to predict 30 and 70% contribution of patient's effort were 0.93 and 0.95, respectively. High sensitivity (all 1.00), specificity (0.86 and 0.78), and negative predictive value (all 1.00), but low positive predictive value (0.61 and 0.43) were obtained to predict either high or low contribution of patient's effort., Conclusion: Our results preliminarily suggested the feasibility of pressure support adjustment according to the PMI target from the ventilator screen. PMI could reliably predict the high and low contribution of a patient's effort during assisted ventilation. Clinical trial registration: ClinicalTrials.gov, identifier NCT05970393., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gao, Zhou, Yang, Xu, Zhou, Zhang and Miao.)

In account of the energy gap law, the development of efficient narrow-band gap thermally activated delayed fluorescence (TADF) materials remains a major challenge for the application of organic light-emitting diodes (OLEDs). The orange-red TADF materials are commonly designed with either large π-conjugated systems or strong intramolecular donor-acceptor (D-A) interactions for red-shift emission and small singlet-triplet energy gap (Δ E ST ). There are rare reports on the simultaneous incorporation of these two strategies on the same material systems. Herein, two orange-red emitters named 1P2D-BP and 2P2D-DQ have been designed by extending the conjugation degree of the center acceptor DQ and increasing the number distribution of the peripheral donor PXZ units, respectively. The emission peak of 1P2D-BP is red-shifted to 615 nm compared to 580 nm for 2P2D-DQ , revealing the pronounced effect of the conjugation extension on the emission band gap. In addition, the distorted molecular structure yields a small Δ E ST of 0.02 eV, favoring the acquisition of a high exciton utilization through an efficient reverse intersystem crossing process. As a result, orange-red OLEDs with both 1P2D-BP and 2P2D-DQ have achieved an external quantum efficiency (EQE) of more than 17%. In addition, the efficient white OLED based on 1P2D-BP is realized through precise exciton assignment and energy transport modulation, showing an EQE of 23.6% and a color rendering index of 82. The present work provides an important reference for the design of high-efficiency narrow-band gap materials in the field of solid-state lighting.

'Human neural stem cells' jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research, is the first guideline for human neural stem cells (hNSCs) in China. This standard specifies the technical requirements, test methods, test regulations, instructions for use, labelling requirements, packaging requirements, storage requirements, transportation requirements and waste disposal requirements for hNSCs, which is applicable to the quality control for hNSCs. It was originally released by the China Society for Cell Biology on 30 August 2022. We hope that publication of the guideline will facilitate institutional establishment, acceptance and execution of proper protocols, and accelerate the international standardization of hNSCs for clinical development and therapeutic applications., (© 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

Human midbrain dopaminergic progenitors (mDAPs) are one of the most representative cell types in both basic research and clinical applications. However, there are still many challenges for the preparation and quality control of mDAPs, such as the lack of standards. Therefore, the establishment of critical quality attributes and technical specifications for mDAPs is largely needed. "Human midbrain dopaminergic progenitor" jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research, is the first guideline for human mDAPs in China. This standard specifies the technical requirements, test methods, inspection rules, instructions for usage, labelling requirements, packaging requirements, storage requirements, transportation requirements and waste disposal requirements for human mDAPs, which is applicable to the quality control for human mDAPs. It was originally released by the China Society for Cell Biology on 30 August 2022. We hope that the publication of this guideline will facilitate the institutional establishment, acceptance and execution of proper protocols, and accelerate the international standardization of human mDAPs for clinical development and therapeutic applications., (© 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

Evidence from animal experiments has shown that chlorinated polyfluoroalkyl ether sulfonic acids (Cl-PFESAs) can induce vision dysfunction in zebrafish. However, environmental epidemiological evidence supporting this hypothesis remains limited. In our case-control study, samples collected from 270 individuals (135 controls and 135 cases) from the Isomers of C8 Health Project data were analyzed for Cl-PFESAs. We also repeated our analysis on zebrafish to support our findings in humans and to decipher the mechanism underlying Cl-PFESA eye toxicity. The serum levels of per- and polyfluoroalkyl substances (PFASs) and alternatives were significantly higher in the cases than in the controls. Higher serum Cl-PFESA levels were associated with greater odds of eye diseases, and the trend showed a statistically significant dose-dependent relationship. The Shapley additive explanations (SHAP) value indicated that 8:2 Cl-PFESA was the dominant eye disease risk factor among the 13 studied PFASs. In zebrafish experiments, Cl-PFESAs induced eye toxicity in adult zebrafish by oxidative damage and cell apoptosis. Compared to the control group, there was significantly reduced thicknesses of the inner plexiform layer (IPL), outer plexiform layer (OPL), and retinal tissue in the zebrafish exposed to Cl-PFESAs. Our study provides human clinical and animal experimental data, showing that exposure to PFASs increases the odds of the development of eye toxicity., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Co-published by Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, and American Chemical Society.)

The progression of autosomal dominant polycystic kidney disease (ADPKD), an inherited kidney disease, is associated with renal interstitial inflammation and fibrosis. CD74 has been known not only as a receptor of macrophage migration inhibitory factor (MIF) it can also have MIF independent functions. In this study, we report unknown roles and function of CD74 in ADPKD. We show that knockout of CD74 delays cyst growth in Pkd1 mutant kidneys. Knockout and knockdown of CD74 (1) normalize PKD associated signaling pathways, including ERK, mTOR and Rb to decrease Pkd1 mutant renal epithelial cell proliferation, (2) decrease the activation of NF-κB and the expression of MCP-1 and TNF-alpha (TNF-α) which decreases the recruitment of macrophages in Pkd1 mutant kidneys, and (3) decrease renal fibrosis in Pkd1 mutant kidneys. We show for the first time that CD74 functions as a transcriptional factor to regulate the expression of fibrotic markers, including collagen I (Col I), fibronectin, and α-smooth muscle actin (α-SMA), through binding on their promoters. Interestingly, CD74 also regulates the transcription of MIF to form a positive feedback loop in that MIF binds with its receptor CD74 to regulate the activity of intracellular signaling pathways and CD74 increases the expression of MIF in ADPKD kidneys during cyst progression. We further show that knockout of MIF and targeting MIF with its inhibitor ISO-1 not only delay cyst growth but also ameliorate renal fibrosis through blocking the activation of renal fibroblasts and CD74 mediated the activation of TGF-β-Smad3 signaling, supporting the idea that CD74 is a key and novel upstream regulator of cyst growth and interstitial fibrosis. Thus, targeting MIF-CD74 axis is a novel therapeutic strategy for ADPKD treatment.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder worldwide and progresses to end-stage renal disease (ESRD). However, its precise mechanism is not fully understood. In recent years, epigenetic reprogramming has drawn increasing attention regarding its effect on cyst growth. However, considering the complexity of epigenetic mechanisms and the broad range of alterations of epigenetic components in ADPKD, identifying more specific epigenetic factors and understanding how they are mechanistically linked to promote cyst growth is relevant for the development of treatment for ADPKD. Here, we find that the histone methyltransferase SMYD3, which activates gene transcription via histone H3 lysine 4 trimethylation (H3K4me3), is upregulated in PKD1 mutant mouse and human ADPKD kidneys. Genetic knockout of SMYD3 in a PKD1 knockout mouse model delayed cyst growth and improved kidney function compared with PKD1 single knockout mouse kidneys. Immunostaining and Western blot assays indicated that SMYD3 regulated PKD1-associated signaling pathways associated with proliferation, apoptosis, and cell cycle effectors in PKD1 mutant renal epithelial cells and tissues. In addition, we found that SMYD3 localized to the centrosome and regulated mitosis and cytokinesis via methylation of α-tubulin at lysine 40. In addition, SMYD3 regulated primary cilia assembly in PKD1 mutant mouse kidneys. In summary, our results demonstrate that overexpression of SMYD3 contributes to cyst progression and suggests targeting SMYD3 as a potential therapeutic strategy for ADPKD.

The plant endophytic bacteria are a great source of nature insecticides. However, no such endophytic bacteria have been found in sugarcane, to address this gap, we isolated and identified a strain of Serratia marcescens with moderate insecticidal activity from sugarcane. Taken armyworm Mythimna separata as example, the mortality rates of oral infection and injection infection were 47.06 % and 91 %, respectively. The SM has significant negative affect on the growth, development, and reproduction of M. separata. After determining that these insecticidal substances, 33 potential virulence proteins were screened through the identification and prediction of bacterial proteins. Later we confirmed serralysin was a vital toxic protein from SM that caused M. separata death by prokaryotic expression. In addition, we also found that the intestinal tissue cells infected with SM or serralysin were severely diseased, which may be a major factor in M. separata demise. Finally, through gene expression level, protein molecular docking, we found the aminopeptidase-N would be one of the potential receptors of serralysin. Taken together, our findings indicate that sugarcane endophyte S. marcescens may be beneficial for pest control in sugarcane and explain its insecticidal mechanism. This study provides new ideas and materials for the biological control of pests., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Abstract: Background. Identifying the causative pathogens of central nervous system infections (CNSIs) is crucial, but the low detection rate of traditional culture methods in cerebrospinal fluid (CSF) has made the pathogenic diagnosis of CNSIs a longstanding challenge. Patients with CNSIs after neurosurgery often overlap with inflammatory and bleeding. Metagenomic next-generation sequencing (mNGS) has shown some benefits in pathogen detection. This study aimed to investigate the diagnostic performance of mNGS in the etiological diagnosis of CNSIs in patients after neurosurgery. Methods. In this prospective observational study, we enrolled patients with suspected CNSIs after neurosurgical operations who were admitted to the intensive care unit of Beijing Tiantan Hospital. All enrolled patients' CSF was tested using mNGS and pathogen culture. According to comprehensive clinical diagnosis, the enrolled patients were divided into CNSIs group and non-CNSIs group to compare the diagnostic efficiency of mNGS and pathogen culture. Results. From December 2021 to March 2023, 139 patients were enrolled while 66 in CNSIs group and 73 in non-CNSIs. The mNGS exceeded culture in the variety and quantity of pathogens detected. The mNGS outperformed traditional pathogen culture in terms of positive percent agreement (63.63%), accuracy (82.01%), and negative predictive value (75.00%), with statistically significant differences ( P < 0.05) for traditional pathogen culture. The mNGS also detected bacterial spectrum and antimicrobial resistance genes. Conclusions. Metagenomics has the potential to assist in the diagnosis of patients with CNSIs who have a negative culture., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)

Background: The aim of the study was to measure empathy in healthcare professionals in Singapore and to compare the scores between the different professions: doctors, nurses, and allied health professionals., Methods: An online survey questionnaire was conducted using the Jefferson Scale of Empathy (JSE) from July 2019 to January 2020. The total JSE score was calculated and compared among the different groups. Multiple linear regression was performed to assess predictors of total empathy scores for groups with statistically lower scores., Results: The survey was completed by 4,188 healthcare professionals (doctors (n=569, 13.6%), nurses (n=3032, 72.4%), and allied health professionals (n=587, 14.0%)) out of the 9,348-strong survey population, with a response rate of 44.8%. The study revealed a mean empathy score (SD) of 103.6 (15.6) for the cohort. The mean empathy score (SD) was 112.3 (14.7), 101.3 (15.2), and 107.0 (15.0), respectively for doctors, nurses, and allied health professionals. These were statistically significantly different among the groups (p< 0.0001), with nurses scoring significantly lower than either doctors (p< 0.0001) or allied health professionals (p< 0.0001). Multiple linear regression showed that age < 30 years old, male gender, Malay ethnicity, and working in a hospital setting were associated with significantly lower empathy scores in the nursing group., Conclusion: Nurses in Singapore had significantly lower empathy scores compared to doctors and allied health professionals. Further research on the underlying causes should be undertaken and measures to improve empathy among Singapore nursing staff should be explored and implemented., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, He et al.)

Metal-hydride-catalyzed alkene hydroalkylation has been developed as an efficient method for C(sp 3 )-C(sp 3 ) coupling with broad substrate availability and high functional group compatibility. However, auxiliary groups, a conjugated group or a chelation-directing group, are commonly required to attain high regio- and enantioselectivities. Herein, we reported a ligand-controlled cobalt-hydride-catalyzed regio-, enantio-, and diastereoselective oxyheterocyclic alkene hydroalkylation without chelation-directing groups. This reaction enables the hydroalkylation of conjugated and unconjugated oxyheterocyclic alkenes to deliver C2- or C3-alkylated tetrahydrofuran or tetrahydropyran in uniformly good yields and with high regio- and enantioselectivities. In addition, hydroalkylation of C2-substituted 2,5-dihydrofuran resulted in the simultaneous construction of 1,3-distereocenters, providing convenient access to polysubstituted tetrahydrofuran with multiple enantioenriched C(sp 3 ) centers.

Background: To evaluate retinal structural and functional changes after silicone oil (SO) removal in eyes with macula-off rhegmatogenous retinal detachment (RRD)., Methods: Best-corrected visual acuity (BCVA) testing, microperimetry, and optical coherence tomography angiography were performed in 48 eyes with macula-off RRD before and 3 months after SO removal. The values of healthy contralateral eyes were used as control data. Correlations between retinal vessel density (VD), retinal nerve fiber layer thickness (RNFLT), the interval between retinal detachment and surgery, the duration of SO tamponade, the follow-up time after SO removal, and visual function were analyzed., Results: Significant increases in 2˚ fixation rate (FR), 4˚ FR, 2˚ mean retinal sensitivity (MRS), 6˚ MRS, parafoveal superficial capillary plexus VD and RNFLT were observed after SO removal (all P < 0.05). The increase of 2˚ MRS and 6˚ MRS were correlated with the duration of SO tamponade and the follow-up time after SO removal respectively (all P < 0.05). The last 2˚ MRS and 6˚ MRS were correlated with the duration of SO tamponade, the interval between retinal detachment and surgery, and the follow-up time after SO removal (all P < 0.01). The last FR in RRD eyes was close to that of contralateral eyes (P > 0.05)., Conclusion: Retinal structure and function improved to different degrees after SO removal. Fixation stability and retinal sensitivity increased more than BCVA postoperatively. Retinal sensitivity, which was affected by the interval between retinal detachment and surgery and the duration of SO tamponade, gradually recovered after SO removal., (© 2023. The Author(s).)

This study aimed to explore the isomer-specific, sex-specific, and joint associations of PFAS and red blood cell indices. We used data of 1,238 adults from the Isomers of C8 Health Project in China. Associations of PFAS isomers and red blood cell indices were explored using multiple linear regression models, Bayesian Kernel Machine Regression models and subgroup analysis across sex. We found that serum concentration of linear (n-) and branched (Br-) isomers of perfluorooctane sulfonate (PFOS) and perfluorohexanesulfonic acid (PFHxS) were significantly associated with red blood cell indices in single-pollutant models, with stronger associations observed for n-PFHxS than Br-PFHxS, in women than in men. For instance, the estimated percentage change in hemoglobin concentration for n-PFHxS (3.65%; 95% CI: 2.95%, 4.34%) was larger than that for Br-PFHxS (0.96%; 95% CI: 0.52%, 1.40%). The estimated percentage change in red blood cell count for n-PFHxS in women (2.55%; 95% CI: 1.81%, 3.28%) was significantly higher than that in men (0.12%; 95% CI: -1.04%, 1.29%) ( P inter < 0.001). Similarly, sex-specific positive association of PFAS mixture and outcomes was observed. Therefore, the structure, susceptive population, and joint effect of PFAS isomers should be taken into consideration when evaluating the health risk of chemicals.

Single cell modification or hybridization technology has become a popular direction in bioengineering in recent years, with applications in clean energy, environmental stewardship, and sustainable human development. Here, we draw attention to nanoarmor, a representative achievement of cytoprotection and functionalization technology. The fundamental principles of nanoarmor need to be studied with input from multiple disciplines, including biology, chemistry, and material science. In this review, we explain the role of nanoarmor and review progress in its applications. We also discuss three main challenges associated with its development: self-driving ability, heterojunction characteristics, and mineralization formation. Finally, we propose a preliminary classification system for nanoarmor., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)