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Abstract Background Vitamin C (vitC) enhances the activity of 2-oxoglutarate-dependent dioxygenases, including TET enzymes, which catalyse DNA demethylation, and Jumonji-domain histone demethylases. The epigenetic remodelling promoted by vitC improves the efficiency of induced pluripotent stem cell derivation, and is required to attain a ground-state of pluripotency in embryonic stem cells (ESCs) that closely mimics the inner cell mass of the early blastocyst. However, genome-wide DNA and histone demethylation can lead to upregulation of transposable elements (TEs), and it is not known how vitC addition in culture media affects TE expression in pluripotent stem cells. Results Here we show that vitC increases the expression of several TE families, including evolutionarily young LINE-1 (L1) elements, in mouse ESCs. We find that TET activity is dispensable for L1 upregulation, and that instead it occurs largely as a result of H3K9me3 loss mediated by KDM4A/C histone demethylases. Despite increased L1 levels, we did not detect increased somatic insertion rates in vitC-treated cells. Notably, treatment of human ESCs with vitC also increases L1 protein levels, albeit through a distinct, post-transcriptional mechanism. Conclusion VitC directly modulates the expression of mouse L1s and other TEs through epigenetic mechanisms, with potential for downstream effects related to the multiple emerging roles of L1s in cellular function.

Yuxuan Zhu,1,2 Jianguo Feng,2 Rongxue Wan,2,3 Wenhua Huang2– 4 1The First Clinical Medical School, Southern Medical University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics, National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, People’s Republic of China; 3Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of China; 4Guangdong Engineering Research Center for Translation of Medical 3D Printing Application, Guangzhou, People’s Republic of ChinaCorrespondence: Rongxue Wan; Wenhua Huang, Email wrx1253071629@163.com; huangwenhua2009@139.comAbstract: Chimeric antigen receptor (CAR) T cell therapy, as an innovative immunotherapy, plays a huge role in current cancer therapy. Although CAR T cell therapy has demonstrated therapeutic effects in some subtypes of B cell leukemia or lymphoma, there are many challenges that limit the therapeutic efficacy of CAR T cells in solid tumors. And how to efficiently transport CAR T cells to tumor tissues is a continuing concern for us. In this review, experiments have been extensively studied and compared. We finally compared the influence of different injection methods on therapeutic efficacy. We also carefully explored the difficulties of designing, homing, and working of CAR T cells, and ultimately came up with better solutions for each process to help CAR T cells reach tumor tissue more efficiently and quickly. These results will have significant implications for guiding CAR T cell therapy in cancer treatment.Keywords: immunotherapy, CAR T cells, metastasis, infiltration, tumor microenvironment

Rong Wan,1 Shengwei Cai,2 Dejian Pan,2 Weilin Yang,2 Rengui Zhou2 1Department of Quality Management, The 904th Hospital of Joint Logistic Support Force (Anhui Medical University Affiliated Wuxi Clinical College), Wuxi, 214044, People’s Republic of China; 2Department of Oncology, The 904th Hospital of Joint Logistic Support Force (Anhui Medical University Affiliated Wuxi Clinical College), Wuxi, 214044, People’s Republic of ChinaCorrespondence: Rong Wan, Department of Quality Management, The 904th Hospital of Joint Logistic Support Force (Anhui Medical University Affiliated Wuxi Clinical College), Xing Yuan North Road 101, Wuxi, 214044, People’s Republic of China, Tel +86 051085142023, Fax +86 051085142601, Email yings2007@21cn.comIntroduction: Postoperative delirium (POD) is one of the prevalent and potentially fatal clinical conditions, leading to high disability and mortality in older patients, as well as increased duration of hospital stay and more hospitalization expenses. There were no effective drugs in the clinical management of POD, and an absence of evidence-based medicine concerning the treatment of POD.Materials and Methods: The present study explored whether atorvastatin (Ato) can decrease the occurrence rate of POD. The present research included patients over the age of 60 who were hospitalized to critical care units (ICUs) following surgery for malignant tumors. Patients received Ato (40mg/day) or placebos utilizing a computer-based random sequencing (in a 1:1 ratio). The primary outcome measure was the occurrence of delirium within the first seven days following surgery.Results: A total of 230 individuals were classified into two groups, namely the placebo group (n=123) and the Ato group (n=107). Patients belonging to two groups had similar baseline clinical data, and there were no statistically significant differences between them. The occurrence of delirium in the Ato group was remarkably reduced unlike the case in the placebo group. 30-day all-cause mortality did not vary significantly between the two groups. Pulmonary infection and Bedsore were significantly decreased in the Ato group than the placebo group, there were no statistically significant differences between the two groups in rhabdomyolysis and abnormal liver enzymes. In terms of medication responses, there were no statistically significant differences between the two groups. Ato patients had remarkably shortened hospital stays and spent remarkably less on hospitalization expenditures in comparison with those in the placebo group.Conclusion: The findings from the present research indicated that Ato can decrease the occurrence of delirium following surgical operation of malignant tumors among elderly patients, it also can reduce the duration of hospitalization, hospital cost, and post-surgical complications, but not improve 30-day all-cause mortality.Registration Number: ChiCTR-IPR-17011984.Keywords: atorvastatin, 30-day all-cause mortality, postoperative delirium, RCT, outcome

Mengxi Xiu,1,2 Xiaohong Zeng,3 Renfeng Shan,1 Wu Wen,1 Jianfeng Li,1 Renhua Wan1 1Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, People’s Republic of China; 2Second Clinical Medical College, Nanchang University, Nanchang, People’s Republic of China; 3Imaging Department, The First Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, People’s Republic of ChinaCorrespondence: Xiaohong ZengImaging Department, The First Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, People’s Republic of ChinaEmail 775112840@qq.comRenhua WanDepartment of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang University, 603 Bayi Road, Nanchang, Jiangxi, 330006, People’s Republic of ChinaTel + 64 (0791)-86360580Email zww726696@sina.comAbstract: The dysregulation of Notch signaling is found in many cancers and is closely related to cancer progression. As an important Notch receptor, abnormal Notch4 expression affects several tumor-cell behaviors, including stemness, the epithelial–mesenchymal transition, radio/chemoresistance and angiogenesis. In order to inhibit the oncogenic effects of Notch4 activation, several methods for targeting Notch4 signaling have been proposed. In this review, we summarize the known molecular mechanisms through which Notch4 affects cancer progression. Finally, we discuss potential Notch4-targeting therapeutic strategies as a reference for future research.Keywords: Notch4 signaling, cancer, cancer stem cell, epithelial–mesenchymal transition, drug resistance, molecular mechanism, therapeutic perspective

Wangwang Yan,1,2,&ast; Yanling Yu,1,2,&ast; Yafei Wang,1 Xue Jiang,1,2 Ruihan Wan,1,3 Chang Ji,1,4 Le Shi,1 Xueqiang Wang,2 Yuling Wang1 1Department of Rehabilitation Medicine, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou City, Guangdong Province, People’s Republic of China; 2Department of Sport Rehabilitation, Shanghai University of Sport, Shanghai, People’s Republic of China; 3Department of Sport Rehabilitation, Shenyang Sport University, Shenyang City, Liaoning Province, People’s Republic of China; 4Postgraduate Research Institute, Guangzhou Sport University, Guangzhou City, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xueqiang WangDepartment of Sport Rehabilitation, Shanghai University of Sport, 188 Hengren Road, Shanghai, 200438, People’s Republic of ChinaEmail wangxueqiang@sus.edu.cnYuling WangDepartment of Rehabilitation Medicine, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Erheng Road, Yuancun, Tianhe District, Guangzhou, 510655, People’s Republic of ChinaEmail wangyul@mail.sysu.edu.cnBackground: Low back pain (LBP) is a highly prevalent musculoskeletal disorder that contributes to the greatest degree of disability worldwide. It has become a very serious public health problem that has attracted considerable research interest. The number of publications associated with LBP and physical activity (PA) is gradually increasing. Nevertheless, few studies have utilised visualisation in analysing the general aspects of this field. Therefore, we aimed to provide a systematic overview of global scientific research related to low back pain and physical activity from 2000 to 2020. It has significant benefits in terms of providing researchers with the status and trends of research on low back pain and physical activity.Methods: Publications on Science Citation Index-Expanded of Web of Science from 2000 to 2020 were searched, and publications relevant to LBP and PA were analysed using Citespace and SPSS. Analyses mainly included cooperation amongst authors, countries and institutions; co-occurrence analysis of keywords; and co-citation analysis of references, revealing productive researchers and contributing institutions tracking the status and trend of research fields.Results: Results of linear regression analysis showed that the number of publications on LBP and PA studies increased significantly (p< 0.001). The subject categories predominantly focused on orthopaedics (2579, 26.54%), rehabilitation (2544, 26.18%) and sport sciences (2015, 25.44%). The United States had the highest number of published papers (2700, 27.789%) and citations (86, 958). In terms of the number of publications, amongst the top 20 journals, Spine contributed the most, whilst the British Journal of Sports Medicine had the highest impact factor (IF2019, 12.022). The University of Sydney had the highest number of publications (330 publications). Maher published the most papers (123 papers) and had the highest H-index (41). Several citation articles and keywords (such as aerobic, obesity and fear-avoidance beliefs) can be used to provide frontier clues for research on LBP and PA.Conclusion: The results of our study may provide information, such as research trends and frontiers of research and collaborating partners, institutions and countries, on LBP and PA.Keywords: low back pain, physical activity, research trends, Web of Science

الملخص: تعتبر متلازمة اليد الغريبة من مضاعفات السكتة الدماغية النادرة. بالرغم من أن حدوث المتلازمة بعد السكتة الدماغية غير شائع، إلإ أنها يمكن أن تسبب أثرا معطلا على نمط الحياة والوظيفة لدى المرضى بعد السكتة الدماغية. ومن الصعب التفريق بين متلازمة اليد الغريبة والجلطة المخية النصف كروية غير السائدة مع أعراض العمى الشقي وإهمال النصف الأيسر، حيث إن المرضى بمتلازمة اليد الغريبة يمكن أيضا أن يكون لديهم إهمال وكذلك أعراض سلوكية، إذا كانت تشمل الفص الجبهي. نحن هنا نصف حالة لرجل عمره ٦٢عاما أُدخل إلى قسم إعادة التأهيل وتم علاجه من الإهمال وتعذر الأداء بعد السكتة الدماغية للشريان الدماغي الأوسط الأيمن. بعد المزيد من التقييم، تم تشخيص المريض بمتلازمة اليد الغريبة. وظيفيا، تم تحسنه واختفت الأعراض بعد أربعة أشهر من السكتة الدماغية. في وصف هذه الحالة، قمنا بإبراز صفات متلازمة اليد الغريبة ونهج علاجها الفريد Abstract: Alien hand syndrome (AHS) is a rare post-stroke complication. Although the occurrence of AHS after stroke is rare, it can have a disabling impact on the lifestyle and career of the patients post stroke. It is difficult to distinguish AHS from the non-dominant hemispheric infarction with symptoms of hemianopia and left hemineglect, as patients with AHS can also have neglect as well as behaviour symptoms if the frontal lobe is involved. We report the case of a 62-year-old gentleman who was admitted to the rehabilitation ward and was treated for neglect and apraxia following right middle cerebral artery stroke. After further re-evaluation, the patient was diagnosed with AHS. Functionally, he improved and the symptoms disappeared four months after the stroke. In this case report, we highlight the features of AHS and provide a unique management approach.

Qiuke Xiao,* Jinwei Ran,* Weizhong Lu, Ruijie Wan, Lujue Dong, Zhenyu Dai Department of Orthopedics, Chongqing Traditional Chinese Medicine Hospital, No.4 Clinical Medicine School of Chengdu University of Traditional Chinese Medicine, Chongqing 400021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhenyu DaiDepartment of Orthopedics, Chongqing Traditional Chinese Medicine Hospital, No.4 Clinical Medicine School of Chengdu University of Traditional Chinese Medicine, Jiangbei District, Chongqing 400021, People’s Republic of ChinaTel/Fax +86 23 6798 3672Email zhenyudai@cdutcm.edu.cnBackground: Increasing attention has been paid to posttraumatic affective disorders. However, orthopedic surgeons dealing with trauma often ignore the harm of such diseases.Objective: To investigate the point prevalence and influencing factors of acute stress disorder (ASD) in elderly patients with osteoporotic fractures (EPOFs) from the perspective of orthopedic surgeons.Patients and Methods: A total of 595 cases of EPOFs were treated at our hospital from January 1, 2018, to June 30, 2019. The patients meeting our inclusion criteria were assessed using a structured interview based on the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria to verify the presence of ASD. After diagnosis, the participants were divided into two groups (those with and without ASD). The sociodemographic characteristics, disease characteristics, and Social Support Rating Scale (SSRS) scores were assessed. The chi-square test was used for univariate analysis, and multivariate analysis was performed using binary logistic regression.Results: Of the 524 participants, 32 (6.1%) met the criteria for the diagnosis of ASD. The results of the univariate analysis showed that gender, personality, living alone, monthly family income, initial fear, poor prognosis expectation, anxiety/depression, pain, and social support were associated with ASD in EPOFs (P< 0.05). The multivariate regression analysis showed that isolation, low monthly family income, introversion, poor prognosis expectation, previous traumatic history, and intense pain were the main influencing factors and risk factors (OR> 1) for ASD in EPOFs.Conclusion: Being female, living alone, introversion, poor family income, intense initial fear, poor prognosis expectation, anxiety/depression, intense pain perception and low social support were significantly related to the occurrence of ASD in EPOFs. To achieve optimal recovery in EPOFs, orthopedic surgeons should meet both the physiological and psychological needs of the patients.Keywords: acute stress disorder, gender, trauma, fracture, elderly

Juan Jiang,1 Rongjun Wan,1 Pinhua Pan,1 Chengping Hu,1 Rihua Zhou,2 Yiping Yin,2 Ting Zhou,2 Hua Huang,2 Yuanyuan Li1 1Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China; 2Medical Center of Tuberculosis, The Second People’s Hospital of Chenzhou, Chenzhou, Hunan Province, People’s Republic of ChinaCorrespondence: Yuanyuan LiDepartment of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha 410008, People’s Republic of ChinaTel +86 13975806790Email leeround@csu.edu.cnHua HuangMedical Center of Tuberculosis, The Second People’s Hospital of Chenzhou, Chenzhou 423000, People’s Republic of ChinaTel +86 18673561888Email huahua1888@foxmail.comBackground: The pandemic of coronavirus disease 2019 (COVID-19) has become a global public health problem. It is important for clinical physicians to differentiate COVID-19 from other respiratory infectious diseases caused by viruses, such as human adenovirus.Subjects and Methods: This was a retrospective observational study. We analyzed and compared the clinical manifestations, laboratory findings and radiological features of two independent cohorts of patients diagnosed with either COVID-19 (n=36) or adenovirus pneumonia (n=18).Results: COVID-19 did not show a preference in males or females, whereas 94.4% of patients with adenovirus pneumonia were males. Fever and cough were common in both COVID-19 and adenovirus pneumonia. But the median maximal body temperature of the adenovirus pneumonia cohort was significantly higher than in COVID-19 (P< 0.001). Furthermore, 77.8% of patients with adenovirus pneumonia had a productive cough versus only 13.9% of COVID-19 patients (P< 0.001). Compared with adenovirus pneumonia, constitutional symptoms were less common in COVID-19, including headache (16.7% vs 38.9%, P=0.072), sore throat (8.3% vs 27.8%, P=0.058), myalgia (8.3% vs 61.1%, P< 0.001) and diarrhea (8.3% vs 44.4%, P=0.002). Furthermore, patients with COVID-19 were less likely to develop respiratory failure (8.3% vs 83.3%, P< 0.001) and showed less prominent laboratory abnormalities, including lymphocytopenia (61.1% vs 88.9%, P=0.035), thrombocytopenia (2.8% vs 61.1%, P< 0.001), elevated procalcitonin (2.8% vs 77.8%, P< 0.001) and elevated C-reactive protein (36.1% vs 100%, P< 0.001). Besides, a higher percentage of patients with adenovirus pneumonia showed elevated transaminase, myocardial enzymes, creatinine and D-dimer compared with COVID-19 patients. On chest CT, the COVID-19 cohort was characterized by peripherally distributed ground-glass opacity and patchy shadowing, while the adenovirus pneumonia cohort frequently presented with consolidation and pleural effusion.Conclusion: There were many differences between patients diagnosed with COVID-19 and those with adenovirus pneumonia in their clinical, laboratory and radiological characteristics. Compared with adenovirus pneumonia, COVID-19 patients tended to show a lower severity of illness.Keywords: coronavirus disease 2019, severe acute respiratory syndrome coronavirus 2, human adenovirus, adenovirus pneumonia, differential diagnosis

Renhui Wan,* Zhengping Ding,* Sheng Xia, Longyi Zheng, Jin Lu Department of Endocrinology, Changhai Hospital, Second Military Medical University, Shanghai 200433, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jin Lu; Longyi ZhengDepartment of Endocrinology, Changhai Hospital, Second Military Medical University, No.168, Changhai Road, Shanghai 200433, People’s Republic of ChinaEmail lujin-sh@139.com; longyizheng111@163.comBackground: Peroxisome proliferator-activated receptor γ2 (PPARγ2) plays a critical role in the regulation of adipocyte differentiation and adipocytokine production. The Pro12Ala variant is the most common mutation in the PPARγ2 gene. Its effect appears to be sensitive to dietary factors, such as docosahexaenoic acid (DHA) level. The purpose of this study was to investigate the interaction effect between PPARγ2 Pro12Ala variant and DHA on the phenotypes of adipocytes.Methods: We generated stable 3T3-L1 cell lines expressing wild-type PPARγ2 or PPARγ2 Pro12Ala variant. These two cell lines were cultured with different concentrations of DHA (0, 50, 200 umol/L). Then Oil red O staining was used to observe cell differentiation and the degree of lipid accumulation, TUNNEL assay was used to detect cell apoptosis, and ELISA assays were used to detect the changes of TNF-α, resistin and adiponectin levels in cell culture supernatant.Results: PPARγ2 Pro12Ala variant reduced lipid droplet accumulation in 3T3-L1 preadipocytes treated with or without 50 μmol/L DHA, but not with 200 μmol/L DHA, compared to that of wild-type PPARγ2. PPARγ2 reduced resistin production and increased adiponectin production in 3T3-L1 adipocytes, whereas PPARγ2 Pro12Ala variant diminished these effects. However, the absence of DHA blocked PPARγ2 Ala12 variant-induced effects on adiponectin production. There was no significant difference in TNF-α secretion between wild-type PPARγ2 and PPARγ2 Pro12Ala cells whether with or without DHA.Conclusion: These results indicated that the effects of PPARγ2 Pro12Ala variant were dependent on DHA concentration.Keywords: peroxisome proliferator-activated receptor γ2, Pro12Ala variant, docosahexaenoic acid, adipocyte, differentiation, adiponectin

Zhenyu Dai,1,* Yue Li,2,* Yonggang Yan,3 Ruijie Wan,1 Qiang Ran,1 Weizhong Lu,1 Bo Qiao,4 Hong Li3 1Department of Orthopedics, Chongqing Traditional Chinese Medicine Hospital, Chongqing, People’s Republic of China; 2Department of Clinical Laboratory, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, People’s Republic of China; 3College of Physical Science and Technology, Sichuan University, Chengdu, People’s Republic of China; 4Department of Orthopedics, the First Affiliated Hospital, Chongqing Medical University, Chongqing, People’s Republic of China *These authors contributed equally to this work Objective: To evaluate the internal fixation effect of nano-calcium-deficient hydroxyapatite/poly-amino acid (n-CDHA/PAA) composite screws in the intraarticular fracture model. Materials and methods: A total of 35 New Zealand White rabbits were used in a bilateral femoral intercondylar fracture model and randomly divided into two groups. n-CDHA/PAA screws were used in the experimental group, and medical metal screws were used in the control group. The fracture condition, range of motion, and the screw push-out strength were assessed, and an arthroscopic examination of knee joint was performed at 4, 8, and 12 weeks after surgery. The biodegradation of the n-CDHA/PAA screws in vivo was tested through weighing, and changes in screw structure were assessed by X-ray diffraction at 12 weeks after surgery. Results: The general situation of all animals was good and showed no incision infection and dehiscence after surgery. X-ray scanning showed that significant callus growth was present in both groups at 4 weeks after surgery, and there was no significant difference (P>0.05) in the Lane-Sandhu score between the experimental and control groups at all time points after surgery. There were no statistically significant differences (P>0.05) in the range of motion and Oswestry Arthroscopy Score of arthroscopic examination of the knee joints between the two groups. The screw push-out strength of the control group was stronger than that of the experimental group at 4 weeks after surgery (P0.05). The degradation tests showed that the n-CDHA/PAA screws degraded gradually after implantation, and the weight loss rate was approximately 16% at 12 weeks after surgery. The X-ray diffraction results showed that the crystal structure of the outer surface of the n-CDHA/PAA screw has changed at 12 weeks after surgery. Conclusion: The n-CDHA/PAA screw is an effective and safe implant as a potential internal fixation device for an intercondylar fracture of the femur, and its internal fixation effect was similar to that of medical metal screw. Keywords: n-CDHA/PAA screw, internal fixation, intraarticular fracture, biocompatibility, bioactivity

Kai Li,1,* Yongxing Zhang,2,* Mengting Chen,1 Yangyang Hu,1 Weiliang Jiang,1 Li Zhou,1 Sisi Li,1 Min Xu,1 Qinghua Zhao,2 Rong Wan1 1Department of Gastroenterology, Shanghai First People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Orthopaedics, Shanghai First People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: To improve the antitumor efficacy of doxorubicin (DOX) and provide novel clinical treatment of gastric cancer, halloysite nanotubes (HNTs) loaded with DOX were encapsulated by soybean phospholipid (LIP) and the formed HNTs/DOX/LIP was systematically characterized via different techniques. The in vitro anticancer activity of HNTs/DOX/LIP was examined using an MTT assay. The antitumor efficacy and biocompatibility were monitored by measuring the tumor volume and assessing the blood routine and serum biochemistry using an ectopic implantation cancer model. The results show that when the concentration of HNTs was 3 mg/mL and the concentration of DOX was 1 mg/mL the optimal DOX loading efficiency was as high as 22.01%±0.43%. In vitro drug release behavior study demonstrated that HNTs/DOX/LIP shows a pH-responsive release property with fast drug release under acidic conditions (pH =5.4). MTT assays and in vivo experimental results revealed that HNTs/DOX/LIP exhibits a significantly higher inhibitory efficacy on the growth of mouse gastric cancer cells than free DOX at the same drug concentration. In addition, the life span of tumor-bearing mice in the HNTs/DOX/LIP-treated group was obviously prolonged compared with the control groups. Moreover, HNTs/DOX/LIP possessed excellent hemocompatibility as shown in the blood and histology studies. These findings indicated that the formed HNTs/DOX/LIP possesses higher antitumor efficacy and may be used as a targeted delivery nanoplatform for targeting therapy of different types of cancer cells. Keywords: HNTs, DOX, gastric cancer, drug carrier

The Trp(620) allotype of PTPN22 confers susceptibility to rheumatoid arthritis (RA) and certain other classical autoimmune diseases. There has been a report of other variants within the PTPN22 locus that alter risk of RA; protective haplotype '5', haplotype group '6-10' and susceptibility haplotype '4', suggesting the possibility of other PTPN22 variants involved in the pathogenesis of RA independent of R620W (rs2476601). Our aim was to further investigate this possibility.A total of 4,460 RA cases and 4,481 controls, all European, were analysed. Single nucleotide polymorphisms rs3789607, rs12144309, rs3811021 and rs12566340 were genotyped over New Zealand (NZ) and UK samples. Publically-available Wellcome Trust Case Control Consortium (WTCCC) genotype data were used.The protective effect of haplotype 5 was confirmed (rs3789607; (OR = 0.91, P = 0.016), and a second protective effect (possibly of haplotype 6) was observed (rs12144309; OR = 0.90, P = 0.021). The previously reported susceptibility effect of haplotype 4 was not replicated; instead a protective effect was observed (rs3811021; OR = 0.85, P = 1.4×10(-5)). Haplotypes defined by rs3789607, rs12144309 and rs3811021 coalesced with the major allele of rs12566340 within the adjacent BFK (B-cell lymphoma 2 (BCL2) family kin) gene. We, therefore, tested rs12566340 for association with RA conditional on rs2476601; there was no evidence for an independent effect at rs12566340 (P = 0.76). Similarly, there was no evidence for an independent effect at rs12566340 in type 1 diabetes (P = 0.85).We have no evidence for a common variant additional to rs2476601 within the PTPN22 locus that influences the risk of RA. Arg620Trp is almost certainly the single common causal variant.

Abstract Background Effective Cataract Surgical Coverage (eCSC) is one of the Universal Health Coverage (UHC) indicators recommended by the World Health Organization (WHO). It is calculated from a population survey and measures access and quality of eye care services in the community. We conducted simultaneous population-based eye surveys in two regions in Malaysia in 2023 to estimate eCSC and compare the results with the survey in 2014 following the implementation of a mobile cataract program. Methods The surveys were simultaneously done in Eastern and Sarawak administrative regions using the Rapid Assessment of Avoidable Blindness (RAAB) technique. It involved a multistage cluster sampling method, each cluster comprising 50 residents aged 50 years and older. Presenting visual acuity (PVA) was checked, and subjects with cataracts were identified. The corrected VA (Pinhole) of those who had undergone cataract surgery was measured. eCSC was calculated at all levels of cataract surgical thresholds according to the protocol. The findings were compared with the previous survey. Results A total of 10,184 subjects were enumerated, with 9,709 examined and 475 non-respondents. Females had a significantly lower Cataract Surgical Coverage (CSC) than males for cataract surgical threshold of

Abstract Employing electrochemistry for the selective functionalization of liquid alkanes allows for sustainable and efficient production of high-value chemicals. However, the large potentials required for C(sp 3)-H bond functionalization and low water solubility of such alkanes make it challenging. Here we discover that a Pt/IrO x electrocatalyst with optimized Cl binding energy enables selective generation of Cl free radicals for C-H chlorination of alkanes. For instance, we achieve monochlorination of cyclohexane with a current up to 5 A, Faradaic efficiency (FE) up to 95% and stable performance over 100 h in aqueous KCl electrolyte. We further demonstrate that our system can directly utilize concentrated seawater derived from a solar evaporation reverse osmosis process, achieving a FE of 93.8% towards chlorocyclohexane at a current of 1 A. By coupling to a photovoltaic module, we showcase solar-driven production of chlorocyclohexane using concentrated seawater in a membrane electrode assembly cell without any external bias. Our findings constitute a sustainable pathway towards renewable energy driven chemicals manufacture using abundant feedstock at industrially relevant rates.

As the level of urbanization in China gradually increases, the effects of urbanization on rainfall-runoff processes have received increasingly widespread attention. Studying the effects of urbanization on rainfall-runoff processes is of significant importance for the prevention and control of urban rainstorm flood disasters. Based on multi-year hourly rainfall-runoff data before and after urbanization in the Dakeng River Basin in Guangzhou, this study analyzes the characteristics of changes in rainfall-runoff processes before and after urbanization using digital filtering and the Boussinesq equation to separate base flow. The results indicate: ① Land use has changed under the increased urbanization rate of the Dakeng River Basin, with natural soil being transformed into impermeable surfaces such as roads, buildings, and other artificial facilities. The increase in impermeable surface area and hardening of underlying surface result in increased surface runoff, peak flow and runoff coefficient, and decreased basin lag time. ② The increase in surface runoff coefficient and peak flow after urbanization is directly proportional to the total precipitation. A possible reason is that the reducing capacity of urban rainwater pipe networks on runoff and the weakening effect of urbanization on infiltration both affect the rainfall-runoff process differently depending on the total precipitation. These changes will pose new challenges for water resources management and flood control in the Dakeng River Basin.

This study' purposes are to synthesize molecularly imprinted polymer (MIP) with hydroxyethyl methacrylate (HEMA) and triethylene glycol dimethacrylate (TEGDMA) using p-xylene under ultraviolet curing at 405 nm for the recognition of hydroquinone (HQ) in aqueous medium. The template was extracted from the polymer with a mixture of methanol and acetic acid (9:1) by volume (v/v). The Fourier transform infrared (FTIR) spectrum of MIP (after wash) showed the absence of peak at the range of 840–860 cm−1, which represented the stretching outside the aromatic plane C–H at the para position (p-xylene). Field emission scanning electron microscope (FESEM) micrograph showed that the MIP had cavities compared to non-imprinted polymer (NIP). The MIP (MIP-Pxy) with ratio (monomer:crosslinker) 0.25 and 1.00% template gave the highest uptake of hydroquinone (HQ) in aqueous solution, which implied more specific recognition (highest KD value). The rebinding of HQ onto MIP-Pxy was best described by both isotherm (Langmuir and Freundlich) and kinetic model (pseudo-first and -second). The MIP was successfully synthesized using p-xylene, able to recognize HQ and was very selective to p-CP. Implication of the study, the synthesized MIP can be used for recognition and sensing materials for HQ and any similar molecules.