Search

Sangsang Xiong,1,* Mingqi Tu,1,* Xiaoting Wu,1 Siying Qu,1 Nisang Chen,1 Junyan Jin,1 Haiqin Rong,1 Shuangyi Pei,2 Jianqiao Fang,1 Xiaomei Shao1 1Key Laboratory for Research of Acupuncture Treatment and Transformation of Emotional Diseases, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaomei Shao; Jianqiao Fang, Zhejiang Chinese Medical University, No. 548, Binwen Road, Binjiang District, Hangzhou City, Zhejiang Province, People’s Republic of China, Tel +86 189 5713 0287, Email shaoxiaomei@zcmu.edu.cn; fangjianqiao7532@163.comBackground: Major depressive disorder (MDD) is highly prevalent, affecting more than 300 million individuals worldwide, and its occurrence may be related to the abnormality of the prefrontal cortex and bilateral temporal cortex. Acupuncture, rooted in the theories of acupoints and meridians, has demonstrated its efficacy in regulating cortical blood flow (CBF) in the brains of MDD patients. As one form of acupuncture, intradermal acupuncture (IA) can alleviate clinical symptoms such as depressive mood and insomnia in MDD patients. However, it remains unknown whether IA will have a specific effect on the prefrontal cortex and bilateral temporal cortex in MDD patients.Methods: In total, 60 participants will be recruited: 20 healthy control participants and 40 MDD patients. All healthy control participants will be allocated to the control group, whereas the 40 MDD patients will be randomly divided into two groups: the gallbladder meridian acupoint (GBA) group and the non-acupoint (NA) group, at a 1:1 allocation ratio. All groups will undergo a one-time IA intervention while their cortical activity is monitored using functional near-infrared spectroscopy (fNIRS). Total hemoglobin, oxygenated hemoglobin, and deoxygenated hemoglobin of the prefrontal and bilateral temporal cortices will be measured by fNIRS during the test procedure.Discussion: This trial aims to use fNIRS to compare real-time hemodynamic changes in the prefrontal and bilateral temporal cortices of healthy individuals and MDD patients during IA. The primary objective is to investigate whether MDD patients exhibit specific real-time responses to IA stimulation in these brain regions. The findings from this study will provide clinical data and a possible theoretical basis for the assumption that stimulation of IA may treat MDD by modulating the relevant brain regions.Trial Registration: The study protocol has been registered in the clinicaltrials.gov with the code NCT05707299.Keywords: major depressive disorder, intradermal acupuncture, functional near-infrared spectroscopy, prefrontal cortex, temporal cortex

Heng Rong,1,&ast; Weixin Dai,1,&ast; Yinying Qin,1,&ast; Zhikeng Meng,2 Xia Zou,3 Binbin Wang,4 Qiufeng Wei,1 Yubo Xie1,5 1Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Anesthesiology, The First People’s Hospital of Yulin, Yulin, People’s Republic of China; 3Department of Anesthesiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China; 4Department of Anesthesiology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 5Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yubo Xie, Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuang-Yong Road, Nanning, Guangxi, 530021, People’s Republic of China, Email xybdoctor@163.comPurpose: In this prospective observational study, an ultrasonographic measurement of antral cross-sectional area (ACSA) was conducted to evaluate the gastric content and volume as well as to identify high-risk stomach in non-pregnant adult surgical patients adhering to preanesthetic fasting guidelines.Patients and Methods: Fasted patients undergoing gastrointestinal endoscopy under sedation were included. Ultrasonographic measurements of ACSA were conducted in both semi-recumbent and right lateral decubitus positions before endoscopic procedures. Gastroscopy was employed to guide the measurement of suctioned gastric volume (GV). Ultrasonography was performed to assess gastric contents and identify patients with high-risk stomach. The relationship between ACSA and suctioned GV was also evaluated.Results: ACSA was evaluated in 736 out of 782 patients. A significant positive correlation was discovered between ACSA in the right lateral decubitus position and suctioned GV, which was more reliable than in the semi-recumbent position. To analyze high-risk stomach with a GV > 100 mL, the cutoff value of ACSA in the right lateral decubitus was found to be 7.5 cm2, with the AUC, sensitivity and specificity of 0.80 (95% CI, 0.76– 0.82; P< 0.001), 82.4% and 67.3%, respectively. A novel mathematical model based on ACSA to estimate GV in non-pregnant fasted adults was presented.Conclusion: Ultrasonographic measurement of ACSA can assist anesthesiologists in estimating the risk of pulmonary aspiration of gastric contents during general anesthesia and sedation.Keywords: gastroscopy, antrum, gastric content, pulmonary aspiration, ultrasonography

Pingyi Wang,1– 3 Hongyan Lu,1– 3 Hao Rong,1– 3 Yuhe Wang,1– 4 Li Wang,1– 3 Xue He,1– 3 Dongya Yuan,1– 3 Yongjun He,1– 3 Tianbo Jin1– 3 1Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, People’s Republic of China; 2Key Laboratory of High Altitude Hypoxia Environment and Life Health, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, People’s Republic of China; 3School of Basic Medical Sciences, Xizang Minzu University, Xianyang, Shaanxi, People’s Republic of China; 4Department of Clinical Laboratory, the Affiliated Hospital of Xizang Minzu University, Xianyang, Shaanxi, People’s Republic of ChinaCorrespondence: Tianbo Jin; Yongjun He, Tel +86-18681940990 ; +86-18691008772, Email jintb@xzmu.edu.cn; 545139647@qq.comBackground: High altitude pulmonary edema (HAPE) is still the most common fatal disease at high altitudes. DNA methylation proceeds with an important role in HAPE progression. This study was designed to investigate the association between CYP39A1 methylation and HAPE.Methods: Peripheral blood samples were enrolled from 106 participants (53 HAPE patients and 53 healthy subjects) to study the association of CYP39A1 methylation with HAPE. DNA methylation site in the promoter region of CYP39A1 was detected by Sequenom MassARRAY EpiTYPER platform.Results: Probability analysis showed that the methylation probabilities of CYP39A1_1_CpG_5 and CYP39A1_3_CpG_21 are significant differences between the cases and controls (p< 0.05). The methylation level analysis indicated that CYP39A1_1_CpG_2.3.4, CYP39A1_5_CpG_6.7, and CYP39A1_5_CpG_9.10 were higher methylation in HAPE compared to the controls (p< 0.05). CYP39A1_3_CpG_21 and CYP39A1_4_CpG_3 exhibited a lower methylation level in HAPE than that in the controls (p< 0.05). The association analysis given that CYP39A1_1_CpG_2.3.4 (OR 2.56, p= 0.035), CYP39A1_5_CpG_6.7 (OR 3.99, p= 0.003), CYP39A1_5_CpG_9.10 (OR 3.99, p= 0.003), CYP39A1_5_CpG_16.17.18 (OR 2.53, p= 0.033), and CYP39A1_5_CpG_20 (OR 3.05, p= 0.031) are associated with an increased risk of HAPE. Whereas CYP39A1_1_CpG_5 (OR 0.33, p= 0.016) and CYP39A1_3_CpG_21 (OR 0.18, p= 0.005) have a protective role in HAPE. Besides, age-stratification analysis showed that CYP39A1_1_CpG_5 (OR 0.16, p= 0.014) and CYP39A1_3_CpG_21 (OR 0.08, p= 0.023) had a protective impact on HAPE in people aged ≤ 32 years. CYP39A1_5_CpG_6.7 (OR 6.70, p= 0.008) and CYP39A1_5_CpG_9.10 (OR 6.70, p= 0.008) were related to an increased susceptibility to HAPE aged > 32 years. Moreover, the diagnostic value of CYP39A1_3_CpG_21 (AUC = 0.712, p< 0.001) was significantly better than other CpG sites.Conclusion: The methylation level of CYP39A1 was associated with a risk of HAPE in the Chinese population, which provided new perspective for preventing and diagnosing of HAPE.Keywords: HAPE, DNA methylation, CYP39A1, CpG, the Chinese population

Yun Wang,1 Xiaohua Liu,2,3 Daihui Peng,2 Yan Wu,2 Yun’ai Su,4 Jia Xu,5 Xiancang Ma,6 Yi Li,7 Jianfei Shi,8 Xiaojing Cheng,9 Han Rong,10 Yiru Fang1,3,11 1Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Psychiatry, Peking University Sixth Hospital, Peking, People’s Republic of China; 5Department of Psychiatry, Harbin First Specific Hospital, Harbin, People’s Republic of China; 6Department of Psychiatry, The First Affiliated Hospital of Xi’an Jiao Tong University, Xi’an, People’s Republic of China; 7Department of Psychiatry, Wuhan Mental Health Center, Wuhan, People’s Republic of China; 8Department of Psychiatry, Hangzhou Seventh People’s Hospital, Hangzhou, People’s Republic of China; 9Department of Psychiatry, Shandong Mental Health Center, Shandong, People’s Republic of China; 10Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen, People’s Republic of China; 11CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai, People’s Republic of ChinaCorrespondence: Daihui Peng; Yiru Fang Email pdhsh@126.com; yirufang@aliyun.comBackground: Despite the best treatments, about 20% of patients with major depressive disorder (MDD) receiving drugs and psychological intervention show little or no improvement. There is no trial comparing different treatment methods in patients with anxiety/somatic subtype MDD.Aim: To compare the efficacy and safety of various treatments in patients with anxiety/somatic subtype MDD.Methods: This was a preliminary multicenter randomized controlled trial at eight participating hospitals in China (09/2016-06/2019) (ClinicalTrials.gov #NCT03219008). The patients were randomized to mirtazapine/SNRIs, mirtazapine/SNRIs+cognitive behavioral therapy (CBT), mirtazapine+SNRIs, or mirtazapine+SNRIs+physical therapies (modified electroconvulsive treatment or repetitive transcranial magnetic stimulation). The primary endpoint was the 17-item Hamilton Depression Scale (HAMD-17). The Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) and Quality of Life (QOL)-6 were the secondary endpoints. The adverse events (AEs) were monitored. The patients were assessed at baseline (0 weeks), and at the end of the 2nd, 4th, 6th, 8th, and 12th week during treatment.Results: Finally, 107 patients were included: mirtazapine/SNRIs (n=36), mirtazapine/SNRIs+CBT (n=28), mirtazapine+SNRIs (n=29), and mirtazapine+SNRIs+physical therapies (n=14). The 17-HDRS and QIDS-SR scores decreased in all four groups, and the QOL-6 scores increased. There were no differences in the 17-HDRS (P=0.099), QIDS-SR (P=0.407), and QOL-6 (P=0.485) scores among the four groups. There were no differences in the occurrence of AEs among the four groups (P=0.942).Conclusion: This preliminary trial suggests that all four interventions (mirtazapine/SNRIs, mirtazapine/SNRIs+CBT, mirtazapine+SNRIs, or mirtazapine+SNRIs+physical therapies) achieved similar response and remission rates in patients with anxiety/somatic subtype MDD. The safety profile was manageable.Keywords: major depressive disorder, anxiety, mirtazapine, serotonin-norepinephrine reuptake inhibitor, cognitive behavioral therapy, Hamilton Depression Scale

Abstract Irrigation with saline groundwater has become necessary to overcome freshwater scarcity in the agricultural industry in arid areas. However, the effects of long-term saline groundwater irrigation on soil salinity and bacterial diversity have rarely been examined. In this study, a Lycium ruthenicum field was divided into two parts and subjected to flooding irrigation with saline groundwater (pH 7.81, total salinity 0.95 g L−1) and surface water (pH 7.76, total salinity 0.36 g L−1) for 8 years. After 8 years of irrigation, the soil salinity and salt ion content (i.e., Na+, Mg2+, K+, Ca2+, Cl− and CO3 2−) in the groundwater irrigation group were significantly greater than those in the surface water irrigation group (p

Abstract Chemotherapy resistance has been a great challenge in pancreatic ductal adenocarcinoma(PDAC) treatments. Current first-line chemotherapy regimens for PDAC include gemcitabine-based regimens such as AG regimen (albumin paclitaxel and gemcitabine), fluorouracil-based regiments such as FOLFIRINOX regimen ((5-fluorouracil5-FU), oxaliplatin, Irinotecan) and platinum-based regimens for patients with BRCA mutations. large amounts of work have been done on exploring the mechanism underlying resistance of gemcitabine-based and platinum-based regimens, while little research has been achieved on the mechanism of FOLFIRINOX regimens resistance. Hence, we identified Polypeptide N-Acetylgalactosaminyltransferase 5, (GALNT5) as a vital regulator and a potential therapeutic target in FOLFIRINOX regimens resistance. Colony formation assays and flow cytometry assays were performed to explore the roles of GALNT5 in cell proliferation and apoptosis in PDAC treated with FOLFIRINOX. IC50 alterations were calculated in GALNT5 knockdown and overexpressed cell lines. RNA-seq followed by GSEA (gene set enrichment analysis) was displayed to explore the potential mechanism. WB (western blotting), real-time PCR, and IF (immunofluorescence) were performed to validate relative pathways. The mouse orthotopic xenograft PDAC model was established to examine GALNT5 functions in vivo. GALNT5 was highly expressed in PDAC tissues and predicted poor prognosis in PDAC. Upregulation of GALNT5 in PDAC cells conferred FOLFIRINOX resistance on PDAC by inhibiting DNA damage. Moreover, GALNT5 interacted with MYH9, thus participating in the activation of the NOTCH pathways, resulting in hampering FOI-induced DNA damage. Functions of GALNT5 promoting FOLFIRINOX resistance were validated in vivo. In this study, we found that aberrantly overexpressed GALNT5 in PDAC took part in the activation of the NOTCH pathway by interacting with MYH9, thus inhibiting the DDR to achieve FOLFIRINOX resistance and causing poor prognosis. We identified GALNT5 as a potential therapeutic target for PDAC patients resistant to FOLFIRINOX chemotherapy.

Abstract Background The effect of supplements on mortality risk in patients with cancer remains uncertain and has scarcely been investigated in subgroups of patients with varying characteristics. This study aimed to investigate the association between two popular supplements, fish oil and glucosamine, and mortality risk in a large population-based cohort and determine whether cardiovascular health and clinical prognosis influence these associations. Methods This prospective cohort study analyzed the data of UK Biobank participants who were diagnosed with cancer. The associations of fish oil and glucosamine consumption with mortality were analyzed using Cox proportional hazards models. Subgroup analyses were performed to assess the effects of Life Essential 8 [LE8] scores (a measure of cardiovascular health) and cancer prognosis (grouped according to the survival rates of specific cancer types) on the associations between supplement use and mortality. Results This analysis included 14,920 participants (mean age = 59.9 years; 60.2% female). One third (34.1%) of the participants reported using fish oil, and one fifth (20.5%) reported using glucosamine. Over a median follow-up of 12.0 years, 2,708 all-cause deaths were registered. The use of fish oil was associated with reduced risks of all-cause mortality (adjusted hazard ratio [aHR] = 0.89, 95% Confidence Interval [CI] = 0.81–0.97) and cancer mortality (aHR = 0.89, 95% CI = 0.81–0.98). Similarly, glucosamine use was associated with reduced risks of all-cause mortality (aHR = 0.83, 95% CI = 0.74–0.92) and cancer mortality (aHR = 0.83, 95% CI = 0.74–0.93) in the fully adjusted model. Subgroup analyses revealed that the protective effects of fish oil and glucosamine against mortality risk were only observed in patients with LE8 scores lower than the mean score or a poor cancer prognosis. Additionally, the association between glucosamine use and a reduced risk of CVD-related mortality was only observed in patients with lower LE8 scores. Conclusions This large cohort study identified the potential differential impact of LE8 scores and cancer prognosis on the associations of fish oil and glucosamine supplementation with survival in patients with cancer. This suggests the importance of considering these factors in future research on supplements and in the provision of personalized integrative cancer care.

Abstract Latexin (LXN) is abundant in macrophages and plays critical roles in inflammation. Much is known about macrophages in atherosclerosis, the role of macrophage LXN in atherosclerosis has remained elusive. Here, the expression of LXN in human and mouse atherosclerotic lesions was examined by immunofluorescence and immunohistochemistry. LXN knockout and LXN/ApoE double-knockout mice were generated to evaluate the functions of LXN in atherosclerosis. Bone marrow transplantation (BMT) experimentation was carried out to determine whether macrophage LXN regulates atherosclerosis. We found that LXN is enriched in human and murine atherosclerotic lesions, mainly localized to macrophages. LXN deletion ameliorated atherosclerosis in ApoE -/- mice. BMT demonstrate that deletion of LXN in bone marrow protects ApoE -/- mice against atherosclerosis. Mechanistically, we found that LXN targets and inhibits JAK1 in macrophages. LXN deficiency stimulates the JAK1/STAT3/ABC transporter pathway, thereby enhancing the anti-inflammatory and anti-oxidant phenotype, cholesterol efflux, subsequently minimizing foam cell formation and atherosclerosis. Gene therapy by treatment of atherosclerotic mice with adeno-associated virus harbouring LXN-depleting shRNA attenuated the disease phenotype. In summary, our study provides new clues for the role of LXN in the pathological regulation of atherosclerosis, and determines that LXN is a target for preventing atherosclerosis, which may be a potential new anti-atherosclerosis therapeutic target.

Abstract Background Transfusion-dependent β-thalassemia (TDT) is one of the global public health concerns highlighted by the World Health Organization. Patients with TDT require regular blood transfusion to survive. However, the availability of blood resources is extremely limited. The purpose of this study was to investigate transfusion burden and willingness to pay (WTP) for temporary remission of anemia status among patients with TDT and to explore the associated factors. Methods Adult patients with TDT were recruited through cluster sampling across several high-incidence provinces in China. Consenting patients completed online questionnaires on demographic information, transfusion burden and WTP with real-time WeChat communication assistance from researchers. The guiding techniques of double-bounded dichotomous choices and open-ended questions in the contingent valuation method (CVM) were used to obtain participants’ WTP for 1 unit of leukocyte-depleted red blood cells. WTP calculations were performed using maximum likelihood estimation, with further insights gained through subgroup analysis based on gender, family monthly income level and convenience of blood transfusion. Results The analysis included 149 TDT patients from five high-incidence provinces, with an average monthly income of $198.5. Patients received an average of 3.7 units per transfusion, 15.4 times annually, with an average WTP of $70.4 per unit (95% CI [62.0, 78.9]). Estimated WTP for temporary anemia alleviation per transfusion totaled $260.6, exceeding monthly income by 1.32 times. Higher WTP was observed among males, higher-income households, and those with at least junior education. Lower WTP was noted among patients with lower transfusion volumes and those needing to travel for transfusion or during hospitalization for blood transfusion. Conclusion High WTP indicated a strong desire for temporary anemia relief. Most TDT patients faced significant economic and transfusion burden. The evident gap in meeting clinical needed underscores the urgent demand for innovative treatments to reduce transfusion dependency, potentially transforming TDT care and improving socioeconomic well-being and clinical outcomes. These findings supported evidence-based decision-making for TDT pharmacoeconomics and efficient healthcare resource allocation in China.

Abstract Background The increasing prevalence of cognitive impairment poses substantial risks to older adults, particularly those with chronic diseases. While existing studies have examined the connection between the empty nest phenomenon and cognitive function, few have attempted to consider endogeneity issues within this relationship, with limited attention given to older adults with chronic diseases. This study investigates the impact of empty nest status on cognitive function among rural Chinese older adults with chronic diseases and explores the possible mechanisms underlying this effect. Methods A cross-sectional study involved 365 older adults aged 60 or above with chronic diseases in rural areas of Shaanxi province, northwest China. Cognitive function was measured using the Mini-Mental State Examination. Multiple regression models and the instrumental variable (IV) method were employed to examine the association between empty nest and cognitive function. Results Among the 365 older adults aged 60 or above with chronic diseases, 43% experienced cognitive impairment. Results from both multiple regression and IV analyses consistently demonstrate a significant association between empty nest status and higher cognitive function scores (β = 1.757, p = 0.007; β = 3.682, p = 0.034, respectively). Mechanism analysis further supports that the positive association may arise from empty nesters receiving more social support from children and friends, and perceiving loneliness experiences as inadequate. Heterogeneity analysis reveals that the association between empty nest status and cognitive function is more pronounced among male adults with chronic diseases. Conclusions This study challenges the notion that empty nest status is a risk factor for cognitive decline in older adults with chronic diseases in rural China. The positive impact is attributed to the robust social relationships of empty nesters, encompassing sustained support from their social network, and the absence of an increase in loneliness. Therefore, future interventions aimed at improving cognitive function in older adults may benefit from promoting the development of social relationships.

Abstract Background Muscle invasive bladder cancer (MIBC) is a life-threatening malignant tumor characterized by high metastasis rates, poor prognosis, and limited treatment options. Immune checkpoint inhibitors (ICIs) targeting PD-1 and PD-L1 represent an emerging treatment for MIBC immunotherapy. However, the characteristics of patients likely to benefit from immunotherapy remain unclear. Methods We performed single-cell mass cytometry (CyTOF) analysis of 179,483 single cells to characterize potential immunotherapy-related cancer stem cells (CSCs)-like populations in the tumor microenvironment of 38 MIBC tissues. The upregulated expression of IGF2BP3 in CD274 + ALDH + CSC-like cells, which was associated with poor clinical prognosis, was analyzed by bulk RNA-sequencing data from an in-house cohort. The functional role of IGF2BP3 was determined through cell proliferation, colony formation, cell apoptosis and sphere formation assays. The regulation of SPHK1 expression by IGF2BP3 was investigated using methylated RNA immunoprecipitation sequencing (MeRIP-seq) and bulk RNA-sequencing (bulk RNA-seq). We further utilized single-nucleus RNA sequencing (snRNA-seq) data from 67,988 cells of 25 MIBC tissues and single-cell RNA sequencing (scRNA-seq) data from MIBC patient-derived organoids to characterize the molecular features of bladder cancer cells co-expressing IGF2BP3 and SPHK1. Spatial transcriptomics (ST) and co-detection by indexing (CODEX) analysis were used to describe the spatial distribution and interactions of IGF2BP3 + SPHK1 + bladder cancer cells and immune cells. Results A subset of CD274 + ALDH + CSC-like cells was identified, associating with immunosuppression and low survival rates in MIBC patients. IGF2BP3, an m6A reader gene, was found to be upregulated in the CD274 + ALDH + CSC-like cell population and linked to poor clinical prognosis in MIBC. Knockout of IGF2BP3 dramatically promoted cell apoptosis and reduced cell proliferation in T24 cells. By integrating MeRIP-seq and bulk RNA-seq analyses, we identified SPHK1 served as a substrate for IGF2BP3 in an m6A-dependent manner. Further snRNA-seq, scRNA-seq, ST, and CODEX analysis revealed a closer topographical distance between IGF2BP3 + SPHK1 + bladder cancer cells and exhausted CD8 + T cells, providing one explanation for the superior response to immunotherapy in IGF2BP3 + SPHK1 + bladder cancer cells-enriched patients. Finally, an ICI-associated signature was developed based on the enriched genes of IGF2BP3 + SPHK1 + bladder cancer cells, and its potential ability to predict the response to immunotherapy was validated in two independent immunotherapy cohort. Conclusions Our study highlighted the critical involvement of the IGF2BP3/SPHK1 signaling in maintaining the stemness of CSCs and promoting MIBC progression. Additionally, these findings suggested that the IGF2BP3/SPHK1 signaling might serve as a biomarker for prognosis and immunotherapy response in MIBC.

Objective The transverse tibial transfer technique is employed primarily to treat diabetic foot ulcers (DFUs), aiming to enhance leg circulation and promote new blood vessel growth. This technique is also beneficial for various conditions associated with poor blood flow in the lower extremities. However, there is no clear molecular mechanism to explain the relationship between the transverse tibial transfer technique and angiogenesis in patients with diabetic foot. This study aims to preliminarily explore the change of IL‐6 and related cytokines in promoting angiogenesis during transverse tibial transplantation, providing a direction for future research. Methods We retrospectively assessed a study from April 2022 to November 2023 on 76 patients with severe DFUs at Wagner stages 3–4. Flow cytometry was used to detect the levels of 12 cytokines in serum before the operation and 3, 7, 14, 21, and 35 days after the operation. Ankle‐brachial index (ABI), transcutaneous oxygen tension (TcPO2), and glycosylated hemoglobin (Hba1c) were recorded at admission and discharge. We examined the variations in cytokine levels, wound healing duration, amputation rates, infection incidence, and other key outcomes. Results In our investigation, a total of 76 individuals participated, comprising 49 males and 27 females. These subjects had an average age of 64.7 years, with a standard deviation of 13 years. The mean ulcer healing time was 74 ± 31 days, amputation occurred in 3 patients, pin tract infection occurred in one patient (1.3%), and incision infection occurred in one patient (1.3%). By day 35 following the surgery, both the ABI and TcPO2 values showed a significant increase from their preoperative levels. HbA1c significantly improved compared with presurgery (p

Abstract Objective To explore the distribution of thrombin–antithrombin complex (TAT), plasmin-α2-antiplasmin inhibitor complex (PIC), thrombomodulin (TM), and tissue plasminogen activator-inhibitor complex (t-PAIC) in healthy older Chinese adults, and establish the reference intervals (RIs). Methods The Biotech Shine i2900 chemiluminescence immune assay was used to measure the plasma concentrations of TAT, PIC, TM, and t-PAIC in 1628 adults ≥ 60 years. The RIs were established using the 2.5th and 97.5th percentiles of the distribution. Results TAT levels were lower in males than females across all ages. Differences between the ages of 60–79 and ≥ 80 in both sex groups were statistically significant, with an upward trend with age. PIC levels showed no difference between the sexes but increased with age in both groups. TM levels did not differ between the sex groups, with slight fluctuation with age. The level in females aged 60–69 was slightly higher than that in the other groups; the difference was statistically significant. T-PAIC levels were not significantly different between the sex groups, with less fluctuation with sex and age. The level in males ≥ 80 years old was slightly lower than that in the other groups; the difference was statistically significant. The RIs for all markers in healthy older Chinese adults were determined and statistically reported by age and sex. For TAT, the RIs for males aged 60–79 and ≥ 80 are 0.51–2.30 ng/mL and 0.88–3.72 ng/mL, respectively, whereas for females aged 60–79 and ≥ 80, the RIs are 0.68–2.82 ng/mL and 1.02–3.67 ng/mL, respectively. For PIC, the RIs for the age groups 60–69, 70–79, and ≥ 80 are 0.10–0.89 µg/mL, 0.12–1.00 µg/mL, and 0.21–1.04 µg/mL, respectively. The RI of TM for females aged 60–69 is 3.32–13.22 TU/mL, whereas it is 2.96–13.26 TU/mL for the other groups. The RI of t-PAIC for males aged ≥ 80 is 1.63–10.68 ng/mL, whereas it is 2.33–11.34 ng/mL for the other groups. Conclusions Discrepancies exist in thrombus markers among different sex and age groups. The RIs of TAT, PIC, TM and t-PAIC for healthy older Chinese adults were successfully established.

Abstract Background It remains unclear which early gestational biomarkers can be used in predicting later development of gestational diabetes mellitus (GDM). We sought to identify the optimal combination of early gestational biomarkers in predicting GDM in machine learning (ML) models. Methods This was a nested case-control study including 100 pairs of GDM and euglycemic (control) pregnancies in the Early Life Plan cohort in Shanghai, China. High sensitivity C reactive protein, sex hormone binding globulin, insulin-like growth factor I, IGF binding protein 2 (IGFBP-2), total and high molecular weight adiponectin and glycosylated fibronectin concentrations were measured in serum samples at 11–14 weeks of gestation. Routine first-trimester blood test biomarkers included fasting plasma glucose (FPG), serum lipids and thyroid hormones. Five ML models [stepwise logistic regression, least absolute shrinkage and selection operator (LASSO), random forest, support vector machine and k-nearest neighbor] were employed to predict GDM. The study subjects were randomly split into two sets for model development (training set, n = 70 GDM/control pairs) and validation (testing set: n = 30 GDM/control pairs). Model performance was evaluated by the area under the curve (AUC) in receiver operating characteristics. Results FPG and IGFBP-2 were consistently selected as predictors of GDM in all ML models. The random forest model including FPG and IGFBP-2 performed the best (AUC 0.80, accuracy 0.72, sensitivity 0.87, specificity 0.57). Adding more predictors did not improve the discriminant power. Conclusion The combination of FPG and IGFBP-2 at early gestation (11–14 weeks) could predict later development of GDM with moderate discriminant power. Further validation studies are warranted to assess the utility of this simple combination model in other independent cohorts.

Abstract Purpose Parastomal hernia (PH) is a frequent complication following radical cystectomy and ileal conduit. The purpose of this study was to summarize the clinical experience and technical characteristics of laparoscopic Sugarbaker repair of PH following radical cystectomy and ileal conduit. Methods We retrospectively evaluated all patients who underwent laparoscopic treatment of PH following radical cystectomy and ileal conduit at Huashan Hospital, Fudan University from May 2013 to December 2022. Results Thirty-five patients were included in the study. Median follow up was 32months (IQR, 25–38 months). Three patients presented with a recurrence (8.6%), with a median time to recurrence of 14 months. Out of the 35 patients, Thirty-two underwent totally laparoscopic repair using the Sugarbaker technique, Three patients required open surgery to repair the intestinal injury after laparoscopic exploration. One patient died 9 months post-surgery due to COVID-19. During the follow-up period, two patients developed a peristomal abscess, and one patient experienced partial intestinal obstruction 10 days after surgery. Conclusion Surgical management of PH following radical cystectomy and ileal conduit is challenging. The laparoscopic Sugarbaker technique for repairing PH following radical cystectomy and ileal conduit has low complication and recurrence rate.

Abstract Enhancing drought tolerance in crops and understanding the underlying mechanisms have been subject of intense research. The precise function and molecular mechanisms of B-box zinc finger proteins (BBX) remain elusive. Here, we report a natural allele of BBX18 (BBX18 TT ) that encodes a C-terminal truncated protein. While most wild tomato germplasms contain the BBX18 CC allele and show more drought tolerant, modern cultivated tomatoes mostly carry BBX18 TT allele and are more drought sensitive. Knockout of BBX18 leads to improved drought tolerance in transgenic plants of cultivated tomato. Ascorbate peroxidase 1 (APX1) is identified as a BBX18-interacting protein that acts as a positive regulator of drought resistance in tomato. Chromatin immunoprecipitation sequencing analyses reveal that BBX18 binds to a unique cis-acting element of the APX1 promoter and represses its gene expression. This study provides insights into the molecular mechanism underlying drought resistance mediated by the BBX18-APX1 module in plants.

Abstract Background Bi-allelic variants in DNAH11 have been identified as causative factors in Primary Ciliary Dyskinesia, leading to abnormal respiratory cilia. Nonetheless, the specific impact of these variants on human sperm flagellar and their involvement in male infertility remain largely unknown. Methods A collaborative effort involving two Chinese reproductive centers conducted a study with 975 unrelated infertile men. Whole-exome sequencing was employed for variant screening, and Sanger sequencing confirmed the identified variants. Morphological and ultrastructural analyses of sperm were conducted using Scanning Electron Microscopy and Transmission Electron Microscopy. Western Blot Analysis and Immunofluorescence Analysis were utilized to assess protein levels and localization. ICSI was performed to evaluate its efficacy in achieving favorable pregnancy outcomes for individuals with DNAH11 variants. Results In this study, we identified seven novel variants in the DNAH11 gene in four asthenoteratozoospermia subjects. These variants led the absence of DNAH11 proteins and ultrastructure defects in sperm flagella, particularly affecting the outer dynein arms (ODAs) and adjacent structures. The levels of ODA protein DNAI2 and axoneme related proteins were down regulated, instead of inner dynein arms (IDA) proteins DNAH1 and DNAH6. Two out of four individuals with DNAH11 variants achieved clinical pregnancies through ICSI. The findings confirm the association between male infertility and bi-allelic deleterious variants in DNAH11, resulting in the aberrant assembly of sperm flagella and contributing to asthenoteratozoospermia. Importantly, ICSI emerges as an effective intervention for overcoming reproductive challenges caused by DNAH11 gene variants.

Titanium hydride (TiH2), a promising high-energy additive, is doped into PTFE/Al to optimize the energy output structure of the reactive jet and strive for better aftereffect damage ability to the target. Six types of PTFE/Al/TiH2 reactive liners with different TiH2 content are prepared by the molding and sintering method. The energy release characteristics of PTFE/Al/TiH2 reactive jet are tested by the transient explosion energy test, and are characterized from pressure and temperature. The reaction delay time, pressure history, and temperature history of the energy release process are obtained, then the actual value of released energy and reaction efficiency of the reactive jet are calculated. The results show that the peak pressure and temperature of the PTFE/Al/TiH2 jet initially increase and then decrease with increasing TiH2 content. When the TiH2 content is 10%, the actual value of released energy and reaction efficiency increased by 24% and 6.4%, respectively, compared to the PTFE/Al jet. The reaction duration of the reactive material is significantly prolonged as the TiH2 content increased from 0% to 30%. Finally, combined with the energy release behaviors of PAT material and the dynamic deformation process of liner, the enhancement mechanism of TiH2 on energy release of the reactive jet is expounded.

Extracting uranium from seawater is an effective strategy for sustainable nuclear fuel supplementation. Uranium in seawater mainly exists in the form of hexavalent uranyl(U(Ⅵ)), although the total amount is large, the mass fraction of U(Ⅵ) is only 3.3×10−9, and many metal ions coexist with uranium. Extracting uranium from seawater is extremely challenging. Electrochemical seawater uranium extraction has become an emerging method for seawater uranium extraction due to its advantages over physical and chemical adsorption processes, such as fast reaction rate, strong anti-interference ability, and simple desorption. However, due to the lack of research on the structure-activity relationship between catalysts and uranium extraction performance, the rational design of highly active electrocatalysts remains a challenge. In this work, we proposed an interface bonding strategy by using a simple hydrothermal method to bond the {2 2 2} fact of octahedral Fe3O4 to the {0 0 2} fact of MoS2. This significantly improves the electron transfer rate at the interface and the cycling stability of Fe3O4, verifying the feasibility of interface bonding for the electrochemical extraction of uranium from seawater. After 7 hours of electrochemical extraction in a simulated solution, the extraction efficiency of uranium can reach 96%. Meanwhile, the experimental results of coexisting ion extraction of uranium indicated that MoS2/Fe3O4 has good selectivity for uranium and anti-interference ability against coexisting ions. Electrochemical extraction is also performed in 10 L natural seawater with a yield of 27.2 μg. The extraction amount of uranium is 5.44 mg/g. A series of characterizations such as XPS and HRTEM, show that Fe3O4 is dispersed on the surface of MoS2 and effectively bound through interfacial interactions. This dispersion effectively solves the aggregation problem of Fe3O4, and the stability of MoS2 structure ensures the cycling stability of Fe3O4. By combining the MoS2 and Fe3O4 at the interface, an efficient electron transfer channel can be constructed, accelerating electron transfer and achieving the goal of simultaneously improving the selectivity, stability, and electron transfer rate of the catalyst. Therefore, the interfacial regulation strategy proposed in this work utilizes the synergistic effects of different components in the composite material to achieve stability and the cyclicity of the catalyst in seawater uranium extraction. At the same time, the interface control strategy will also provide a feasible solution for achieving efficient reduction and extraction of uranyl in a series of complex environments such as seawater. And the electron transfer path and the species change of uranium during catalytic reduction need to be further explored in the mechanism analysis in this work.

Uranium, as the most important fuel for nuclear power operation, is crucial to ensure the sustainable development of nuclear power. However, the supply-demand contradiction of uranium resources in China has become increasingly prominent, and the gap needs to be filled by overseas development and international market procurement. The photoreduction and electroreduction of uranium under complex conditions are mainly targeted at uranium containing radioactive wastewater, real seawater, and other systems. Uranium containing radioactive wastewater comes from the processes of uranium mining, uranium enrichment, uranium conversion, and manufacture of nuclear fuel elements, with the characteristics of complex interfering ions. Although the total amount of uranium in seawater is very large, the concentration of uranium in seawater is low, making the extraction of uranium from seawater extremely challenging. On the one hand, the reserves of uranium in seawater are nearly a thousand times higher than those on land; on the other hand, the entire application process of the nuclear industry produces a large amount of uranium containing radioactive wastewater. If efficient separation of uranium from seawater and uranium containing radioactive wastewater can be achieved, it can promote the secondary supply of uranium resources and alleviate the supply-demand contradiction of uranium resources in China. Therefore, the development of uranium recovery and extraction technology from seawater and uranium containing radioactive wastewater is important for the sustainable development of the nuclear industry. This paper reviews the recent research progress in separating uranium in complex environments such as seawater and uranium containing radioactive wastewater. In terms of uranium speciation analysis, it describes the coordination environment of complex environmental uranyl and summarizes the advantages of photocatalysis and electrocatalysis in the fields of uranium extraction from uranium containing radioactive wastewater and seawater. In terms of designing photocatalysts, strategies such as element doping, metal loading, defect engineering, and introducing heterojunctions have been summarized for the preparation of photocatalytic semiconductor materials. The modification of functional groups on heterojunctions to regulate their energy band structure had introduced, which improved the overall performance of the material. The integration of selective adsorption and catalytic reduction, electrochemical methods can reduce soluble uranyl ions to neutral and insoluble products for separation, with advantages such as fast kinetics, wide extraction concentration range, and large separation capacity. However, there are also many key technical challenges in the practical application process, such as the competition between multiple cations and uranyl ions in complex systems, and the problem of excessive energy consumption caused by the competing reaction of water splitting during the cathodic uranium extraction process. In terms of electrocatalysis, various aspects such as electrode carrier selection, electrochemical device design, defect engineering, surface engineering, interface engineering, and microbial electrochemistry have been summarized to design electrocatalytic materials. In terms of key technical bottlenecks, combining photocatalysis and electrocatalysis technology with challenges in complex scenarios such as uranium speciation analysis, material functionalization design, intermediate reaction species analysis, uranium extraction mechanism analysis, cost control, and real-world application outcomes, relevant research have focused on challenges such as efficient photocatalytic reduction of uranium under natural light, identification of intermediate uranium species, uranium extraction from uranium containing radioactive wastewater, and seawater extraction from real ocean environments.

Abstract Background Childhood maltreatment (CM) is linked to long-term adverse health outcomes, including accelerated biological aging and cognitive decline. This study investigates the relationship between CM and various aging biomarkers: telomere length, facial aging, intrinsic epigenetic age acceleration (IEAA), GrimAge, HannumAge, PhenoAge, frailty index, and cognitive performance. Methods We conducted a Mendelian randomization (MR) study using published GWAS summary statistics. Aging biomarkers included telomere length (qPCR), facial aging (subjective evaluation), and epigenetic age markers (HannumAge, IEAA, GrimAge, PhenoAge). The frailty index was calculated from clinical assessments, and cognitive performance was evaluated with standardized tests. Analyses included Inverse-Variance Weighted (IVW), MR Egger, and Weighted Median (WM) methods, adjusted for multiple comparisons. Results CM was significantly associated with shorter telomere length (IVW: β = − 0.1, 95% CI − 0.18 to − 0.02, pFDR = 0.032) and increased HannumAge (IVW: β = 1.33, 95% CI 0.36 to 2.3, pFDR = 0.028), GrimAge (IVW: β = 1.19, 95% CI 0.19 to 2.2, pFDR = 0.040), and PhenoAge (IVW: β = 1.4, 95% CI 0.12 to 2.68, pFDR = 0.053). A significant association was also found with the frailty index (IVW: β = 0.31, 95% CI 0.13 to 0.49, pFDR = 0.006). No significant associations were found with facial aging, IEAA, or cognitive performance. Conclusions CM is linked to accelerated biological aging, shown by shorter telomere length and increased epigenetic aging markers. CM was also associated with increased frailty, highlighting the need for early interventions to mitigate long-term effects. Further research should explore mechanisms and prevention strategies.

Abstract Immune evasion of Mycobacterium tuberculosis (Mtb) facilitates intracellular bacterial growth. The mechanisms of immune evasion, however, are still not fully understood. In this study, we reveal that tristetraprolin (TTP), one of the best characterized RNA‐binding proteins controlling the stability of targeted mRNAs, mediates innate immune evasion of mycobacteria. We found that TTP knockout mice displayed reduced bacterial burden in the early stage after Mtb aerosol challenge. Macrophages deficient in TTP also showed an inhibition in intracellular mycobacterial growth. Live mycobacteria induced TTP protein expression in macrophages, which was blocked by the mTOR inhibitor rapamycin. Rapamycin and AZD8055 specifically blocked 4EBP1 phosphorylation in infected macrophages and suppressed intracellular BCG growth. Rapamycin promoted TTP protein degradation through the ubiquitination pathway, whereas the proteasome inhibitor MG‐132 blocked rapamycin function and thus stabilized TTP protein. TTP induction suppressed the expression of iNOS/TNF‐α/IL‐12/IL‐23, and weakened protective immune responses in macrophages, whereas rapamycin enhanced the bactericidal effects through TTP inhibition. Moreover, blocking TTP binding increased the expression of TNF‐α and iNOS and suppressed intracellular mycobacterial growth. Overall, our study reveals a novel role for RNA‐binding protein TTP in Mtb immune evasion mechanisms and provides a potential target for host‐directed therapy against tuberculosis (TB).

Abstract Background Hepatitis B virus (HBV) infection poses a substantial threat to human health, impacting not only infected individuals but also potentially exerting adverse effects on the health of their offspring. The underlying mechanisms driving this phenomenon remain elusive. This study aims to shed light on this issue by examining alterations in paternally imprinted genes within sperm. Methods A cohort of 35 individuals with normal semen analysis, comprising 17 hepatitis B surface antigen (HBsAg)-positive and 18 negative individuals, was recruited. Based on the previous research and the Online Mendelian Inheritance in Man database (OMIM, https://www.omim.org/ ), targeted promoter methylation sequencing was employed to investigate 28 paternally imprinted genes associated with various diseases. Results Bioinformatic analyses revealed 42 differentially methylated sites across 29 CpG islands within 19 genes and four differentially methylated CpG islands within four genes. At the gene level, an increase in methylation of DNMT1 and a decrease in methylation of CUL7, PRKAG2, and TP53 were observed. DNA methylation haplotype analysis identified 51 differentially methylated haplotypes within 36 CpG islands across 22 genes. Conclusions This is the first study to explore the effects of HBV infection on sperm DNA methylation and the potential underlying mechanisms of intergenerational influence of paternal HBV infection.

Abstract Introduction Highly myopic macular hole retinal detachment (MHRD) is often associated with a poor prognosis, and there is currently no optimal treatment. Platelet-rich fibrin (PRF), an autologous blood product, has been shown to promote tissue regeneration. This prospective, randomized, controlled study investigated the efficacy of conventional internal limiting membrane (ILM) peeling versus PRF membrane transplantation in highly myopic MHRD. Methods Eyes with highly myopic MHRD were randomly assigned to either a conventional ILM peeling group (IP group, n = 19) or a PRF membrane transplantation group (PMT group, n = 21). The study followed participants for a period of 6 months. The primary outcome measure was macular hole (MH) closure assessed using optical coherence tomography. Secondary outcomes included best-corrected visual acuity (BCVA), central retinal thickness (CRT), superficial vascular density (SVD), deep vascular density (DVD), rate of retinal reattachment, and any complications encountered. Results MH closure was achieved in a significantly greater proportion of eyes in the PMT group (21/21, 100.00%) compared to the IP group (15/19, 78.95%) (P = 0.042). Retinal reattachment was accomplished in all patients (100.00%) within both groups. Except for an insignificant difference in BCVA observed at 1 week post-surgery in the IP group, significant improvements in BCVA and CRT were documented in both groups across all other post-operative time points. Final BCVA (P = 0.040), CRT (P = 0.002), SVD (P = 0.002), and DVD (P = 0.013) were all significantly higher in the PMT group compared to the IP group. No serious complications were identified in either group. Conclusions This study demonstrated the superiority of PRF membrane transplantation compared to conventional ILM peeling in promoting MH closure and enhancing retinal vascular density in patients with highly myopic MHRD. Additionally, PRF membrane transplantation effectively restores retinal reattachment, improves visual function, and increases retinal thickness without introducing additional complications. Trial Registration Number www.clinicaltrials.gov , NCT06200727.

Children and adults differ significantly in physiology, biochemistry and immune function, which leads to significant differences in blood transfusion strategies between children and adults. To guide the clinical transfusion practice of pediatric patients and improve the prognosis of children, the National Health Commission organized the formulation and release of the health industry standard Guideline for Pediatric Transfusion (WS/T 795-2022).This paper will briefly introduce some concepts that help understand of the Standard and the preparation process of the Standard, and explain and interpret the preparation of the " scope", " general provisions" and " factors to consider" of the Standard, hoping to contribute to the understanding and implementation of the Standard.

Abstract Calcific aortic valve disease (CAVD) is becoming an increasingly important global medical problem, but effective pharmacological treatments are lacking. Noncoding RNAs play a pivotal role in the progression of cardiovascular diseases, but their relationship with CAVD remains unclear. Sequencing data revealed differential expression of many noncoding RNAs in normal and calcified aortic valves, with significant differences in circHIPK3 and miR-182-5p expression. Overexpression of circHIPK3 ameliorated aortic valve lesions in a CAVD mouse model. In vitro experiments demonstrated that circHIPK3 inhibits the osteogenic response of aortic valve interstitial cells. Mechanistically, DEAD-box helicase 5 (DDX5) recruits methyltransferase 3 (METTL3) to promote the N6-methyladenosine (m6A) modification of circHIPK3. Furthermore, m6A-modified circHIPK3 increases the stability of Kremen1 (Krm1) mRNA, and Krm1 is a negative regulator of the Wnt/β-catenin pathway. Additionally, miR-182-5p suppresses the expression of Dickkopf2 (Dkk2), the ligand of Krm1, and attenuates the Krm1-mediated inhibition of Wnt signaling. Activation of the Wnt signaling pathway significantly contributes to the promotion of aortic valve calcification. Our study describes the role of the Krm1-Dkk2 axis in inhibiting Wnt signaling in aortic valves and suggests that noncoding RNAs are upstream regulators of this process.

Abstract Background This study investigated the molecular mechanism of long intergenic non-protein coding RNA 1605 (LINC01605) in the process of tumor growth and liver metastasis of pancreatic ductal adenocarcinoma (PDAC). Methods LINC01605 was filtered out with specificity through TCGA datasets (related to DFS) and our RNA-sequencing data of PDAC tissue samples from Renji Hospital. The expression level and clinical relevance of LINC01605 were then verified in clinical cohorts and samples by immunohistochemical staining assay and survival analysis. Loss- and gain-of-function experiments were performed to estimate the regulatory effects of LINC01605 in vitro. RNA-seq of LINC01605-knockdown PDAC cells and subsequent inhibitor-based cellular function, western blotting, immunofluorescence and rescue experiments were conducted to explore the mechanisms by which LINC01605 regulates the behaviors of PDAC tumor cells. Subcutaneous xenograft models and intrasplenic liver metastasis models were employed to study its role in PDAC tumor growth and liver metastasis in vivo. Results LINC01605 expression is upregulated in both PDAC primary tumor and liver metastasis tissues and correlates with poor clinical prognosis. Loss and gain of function experiments in cells demonstrated that LINC01605 promotes the proliferation and migration of PDAC cells in vitro. In subsequent verification experiments, we found that LINC01605 contributes to PDAC progression through cholesterol metabolism regulation in a LIN28B-interacting manner by activating the mTOR signaling pathway. Furthermore, the animal models showed that LINC01605 facilitates the proliferation and metastatic invasion of PDAC cells in vivo. Conclusions Our results indicate that the upregulated lncRNA LINC01605 promotes PDAC tumor cell proliferation and migration by regulating cholesterol metabolism via activation of the mTOR signaling pathway in a LIN28B-interacting manner. These findings provide new insight into the role of LINC01605 in PDAC tumor growth and liver metastasis as well as its value for clinical approaches as a metabolic therapeutic target in PDAC.

Abstract Despite extensive research on the relationship between choline and cardiovascular disease (CVD), conflicting findings have been reported. We aim to investigate the relationship between choline and CVD. Our analysis screened a retrospective cohort study of 14,663 participants from the National Health and Nutrition Examination Survey conducted between 2013 and 2018. Propensity score matching and restricted cubic splines was used to access the association between choline intake and the risk of CVD. A two-sample Mendelian randomization (MR) analysis was conducted to examine the potential causality. Additionally, sets of single cell RNA-sequencing data were extracted and analyzed, in order to explore the role of choline metabolism pathway in the progression and severity of the CVD and the underlying potential mechanisms involved. The adjusted odds ratios and 95% confidence intervals for stroke were 0.72 (0.53–0.98; p = 0.035) for quartile 3 and 0.54 (0.39–0.75; p

Abstract Background Genetic disorders often manifest as abnormal fetal or childhood development. Copy number variations (CNVs) represent a significant genetic mechanism underlying such disorders. Despite their importance, the effectiveness of clinical exome sequencing (CES) in detecting CNVs, particularly small ones, remains incompletely understood. We aimed to evaluate the detection of both large and small CNVs using CES in a substantial clinical cohort, including parent–offspring trios and proband only analysis. Methods We conducted a retrospective analysis of CES data from 2428 families, collected from 2018 to 2021. Detected CNV were categorized as large or small, and various validation techniques including chromosome microarray (CMA), Multiplex ligation-dependent probe amplification assay (MLPA), and/or PCR-based methods, were employed for cross-validation. Results Our CNV discovery pipeline identified 171 CNV events in 154 cases, resulting in an overall detection rate of 6.3%. Validation was performed on 113 CNVs from 103 cases to assess CES reliability. The overall concordance rate between CES and other validation methods was 88.49% (100/113). Specifically, CES demonstrated complete consistency in detecting large CNV. However, for small CNVs, consistency rates were 81.08% (30/37) for deletions and 73.91% (17/23) for duplications. Conclusion CES demonstrated high sensitivity and reliability in CNV detection. It emerges as an economical and dependable option for the clinical CNV detection in cases of developmental abnormalities, especially fetal structural abnormalities.

Abstract Introduction Intracerebral hemorrhage (ICH) is a severe manifestation of stroke, demonstrating notably elevated global mortality and morbidity. Thus far, effective therapeutic strategies for ICH have proven elusive. Currently, minimally invasive techniques are widely employed for ICH management, particularly using endoscopic hematoma evacuation in cases of deep ICH. Exploration of strategies to achieve meticulous surgery and diminish iatrogenic harm, especially to the corticospinal tract, with the objective of enhancing the neurological prognosis of patients, needs further efforts. Methods We comprehensively collected detailed demographic, clinical, radiographic, surgical, and postoperative treatment and recovery data for patients who underwent endoscopic hematoma removal. This thorough inclusion of data intends to offer a comprehensive overview of our technical experience in this study. Results One hundred fifty-four eligible patients with deep supratentorial intracerebral hemorrhage who underwent endoscopic hematoma removal were included in this study. The mean hematoma volume was 42 ml, with 74 instances of left-sided hematoma and 80 cases of right-sided hematoma. The median Glasgow Coma Scale (GCS) score at admission was 10 (range from 4 to 15), and the median time from symptom onset to surgery was 18 (range 2 to 96) h. The mean hematoma clearance rate was 89%. The rebleeding and mortality rates within 1 month after surgery were 3.2% and 7.8%, respectively. At the 6-month mark, the proportion of patients with modified Rankin Scale (mRS) scores of 0–3 was 58.4%. Conclusion Both the reduction of surgery-related injury and the protection of the residual corticospinal tract through endoscopic hematoma removal may potentially enhance neurological functional outcomes in patients with deep ICH, warranting validation in a forthcoming multicenter clinical study.

An extreme heavy rainfall event struck the northern part of the Guilin urban area in the early morning of May 22, 2023, breaking local historical records for both hourly and three-hourly precipitation, resulting in severe urban waterlogging. Analysis was conducted using data from routine observation, ground-based dense automatic stations, Doppler weather radar, and ERA5 reanalysis. The results are as follows. (1) This event occurred on the edge of the subtropical high-pressure system, with the continuous strengthening of the southwest jet stream providing abundant moisture and energy for the extreme rainfall under the influence of the low-level shear line and the southward movement of the surface cold front. (2) The echoes of heavy rainfall evolved into a linear convection, which changed the direction and shape when timely met with the surface cold air. Meanwhile, the continuously developing new individual cells on its western side joined to form a "train effect," leading to extreme rainfall. The echo exhibited characteristics of low core and high efficiency. (3) The timely intrusion of weak cold air intensified convective rainfall and enhanced cold pool outflow, triggering new convection in the warm and moist region ahead of it, which favored the development and persistence of heavy rainfall. (4) During the eastward movement of individual convective cells, they merged through cloud bridges and expanded through cloud development, forming new cloud clusters and rapidly intensifying precipitation. The interaction and merging of convective cells were the main mechanisms for the prolonged and intensified heavy rainfall. (5) Various numerical models underestimated the intensity of this event, with biases in forecasting the rainfall center mainly due to deviations in the timing of forecasting the influence of surface cold air.

Abstract Complicated associations between multiplexed environmental factors and aging are poorly understood. We manipulated aging using multidimensional metrics such as phenotypic age, brain age, and brain volumes in the UK Biobank. Weighted quantile sum regression was used to examine the relative individual contributions of multiplexed environmental factors to aging, and self-organizing maps (SOMs) were used to examine joint effects. Air pollution presented a relatively large contribution in most cases. We also found fair heterogeneities in which the same environmental factor contributed inconsistently to different aging metrics. Particulate matter contributed the most to variance in aging, while noise and green space showed considerable contribution to brain volumes. SOM identified five subpopulations with distinct environmental exposure patterns and the air pollution subpopulation had the worst aging status. This study reveals the heterogeneous associations of multiplexed environmental factors with multidimensional aging metrics and serves as a proof of concept when analyzing multifactors and multiple outcomes.

Abstract Osteoarthritis (OA) is the most common degenerative joint disorder that causes disability in aged individuals, caused by functional and structural alterations of the knee joint. To investigate whether metabolic drivers might be harnessed to promote cartilage repair, a liquid chromatography–mass spectrometry (LC–MS) untargeted metabolomics approach was carried out to screen serum biomarkers in osteoarthritic rats. Based on the correlation analyses, α-ketoglutarate (α-KG) has been demonstrated to have antioxidant and anti-inflammatory properties in various diseases. These properties make α-KG a prime candidate for further investigation of OA. Experimental results indicate that α-KG significantly inhibited H2O2-induced cartilage cell matrix degradation and apoptosis, reduced levels of reactive oxygen species (ROS) and malondialdehyde (MDA), increased superoxide dismutase (SOD) and glutathione (GSH)/glutathione disulfide (GSSG) levels, and upregulated the expression of ETV4, SLC7A11 and GPX4. Further mechanistic studies observed that α-KG, like Ferrostatin-1 (Fer-1), effectively alleviated Erastin-induced apoptosis and ECM degradation. α-KG and Fer-1 upregulated ETV4, SLC7A11, and GPX4 at the mRNA and protein levels, decreased ferrous ion (Fe2+) accumulation, and preserved mitochondrial membrane potential (MMP) in ATDC5 cells. In vivo, α-KG treatment inhibited ferroptosis in OA rats by activating the ETV4/SLC7A11/GPX4 pathway. Thus, these findings indicate that α-KG inhibits ferroptosis via the ETV4/SLC7A11/GPX4 signaling pathway, thereby alleviating OA. These observations suggest that α-KG exhibits potential therapeutic properties for the treatment and prevention of OA, thereby having potential clinical applications in the future.

A ternary system of PTFE/Al/Bi2O3 is constructed by incorporating PTFE-based reactive material and thermite for enhancing the energy release of the PTFE-based reactive material. The effects of Bi2O3 in the PTFE/Al/Bi2O3 on both mechanical properties and the energy release were investigated through various tests such as thermogravimetry-differential scanning calorimetry, adiabatic oxygen bomb test and split Hopkinson pressure bar test. The microstructure observed through scanning electron microscope and X-ray diffraction results are used to analyze the ignition and reaction mechanism of PTFE/Al/Bi2O3. The results indicate that the PTFE/Al/Bi2O3 are capable of triggering the exothermic reaction of molten PTFE/Bi2O3 and Al/Bi2O3 over the PTFE/Al reactive materials, thereby promoting reactions. The excessive aluminum in the ternary system is beneficial for increasing energy release. The ignition of shock-induced chemical reactions in PTFE/Al/Bi2O3 is closely related to the material fracture. The dominant mechanism for hot-spot generation under Split Hopkinson Pressure Bar test is the frictional temperature rise at the microcrack after failure.

Objective To investigate the status quo of health literacy among military personnel stationing on plateau and analyze its influencing factors. Methods National Health Literacy Monitoring Questionnaire (2015), self-made questionnaire for demographic data based on literature, Connor-Davidson Resilience Scale, Simplified Coping Style Questionnaire, and Positive and Negative Affect Scale were employed to survey 2 516 officers and soldiers stationing on plateau with aid of a WeChat APP Questionnaire Star. Their current status of health literacy and its influencing factors were analyzed. Results The survey results showed that the overall health literacy level was 20.03% among the 2 516 participants. The literacy levels of basic knowledge and concepts, healthy lifestyles and behaviors, and health skills were 31.08%, 26.23%, and 26.63%, respectively, and the health literacy levels of scientific health concepts, infectious disease prevention and treatment, chronic disease prevention and treatment, safety and first aid, basic medical care, and health information were 40.58%, 19.36%, 9.62%, 82.75%, 29.61%, and 45.03%, respectively. Multivariate unconditional logistic regression analysis indicated that the influencing factors of health literacy level were years of working (OR=1.857, 95%CI: 1.391~2.479; OR=4.657, 95%CI: 3.297~6.578), ethnicity (OR=0.394, 95%CI: 0.251~0.620), marriage (OR=0.609, 95%CI: 0.430~0.861), only-child family (OR=0.759, 95%CI: 0.585~0.985), home location (OR=0.545, 95%CI: 0.359~0.827), smoking (OR=1.579, 95%CI: 1.254~1.988), education level (OR=3.638, 95%CI: 1.500~8.822), weekly online game time (OR=0.517, 95%CI: 0.365~0.731; OR=0.351, 95%CI: 0.172~0.716), number of physical checkups per year (OR=3.251, 95%CI: 1.359~7.778; OR= 4.545, 95%CI: 1.841~11.221), father's occupation (OR=5.185, 95%CI: 1.800~14.933; OR=3.229, 95%CI: 1.261~8.270), mother's occupation (OR=0.221, 95%CI: 0.086~0.568; OR=0.218, 95%CI: 0.081~0.587; OR=0.046, 95%CI: 0.018~0.118), positive coping (OR=1.052, 95%CI: 1.033~1.072), and negative coping (OR=0.950, 95%CI: 0.929~0.972). Conclusion The overall health literacy level is quite low among the plateau military personnel in this ministry, and the relevant departments should actively explore effective interventions to comprehensively improve their health literacy based on the influencing factors.

Abstract The envelope (E) protein of the Japanese encephalitis virus (JEV) is a key protein for virus infection and adsorption of host cells, which determines the virulence of the virus and regulates the intensity of inflammatory response. The mutation of multiple aa residues in the E protein plays a critical role in the attenuated strain of JEV. This study demonstrated that the Asp to Gly, Ser, and His mutation of the E389 site, respectively, the replication ability of the viruses in cells was significantly reduced, and the viral neuroinvasiveness was attenuated to different degrees. Among them, the mutation at E389 site enhanced the E protein flexibility contributed to the attenuation of neuroinvasiveness. In contrast, less flexibility of E protein enhanced the neuroinvasiveness of the strain. Our results indicate that the mechanism of attenuation of E389 aa mutation attenuates neuroinvasiveness is related to increased flexibility of the E protein. In addition, the increased flexibility of E protein enhanced the viral sensitivity to heparin inhibition in vitro, which may lead to a decrease in the viral load entering brain. These results suggest that E389 residue is a potential site affecting JEV virulence, and the flexibility of the E protein of aa at this site plays an important role in the determination of neuroinvasiveness.