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Taomei Li, Lu Tan, Fei Lei, Xiangdong Tang Sleep Medicine Center, Mental Health Center, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Xiangdong Tang, Sleep Medicine Center, Mental Health Center, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, 28 Dian Xin Nan Jie, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-28-85422733, Fax +86-28-85422632, Email 2372564613@qq.comBackground: White blood cell (WBC) and its subset counts are standard, inexpensive, direct markers of inflammation. Obstructive sleep apnea (OSA) is implicated in changes in inflammation markers, and sex differences are evident in both OSA and inflammation. It is unknown whether sex modulates the relationship between OSA severity and leukocyte measures.Methods: 1222 patients (914 males, 308 females) underwent overnight laboratorial polysomnography and measurement of WBC and its subset (lymphocyte, neutrophil, monocyte) counts. Patients were divided into primary snoring and mild, moderate, and severe OSA groups, and differences in leukocyte parameters were analyzed separately by sex in multivariable analyses.Results: In multiple regression models, higher apnea-hypopnea index (AHI) was independently associated with neutrophil counts only in men, and with higher total WBC, lymphocyte and monocyte counts both in women and men. Further ordinal logistic regression analysis revealed a significant association between AHI and total WBC (OR 1.87, 95% CI 1.09– 3.23) and neutrophil (OR 1.77, 95% CI 1.02– 3.07) counts in men only. Correlation analysis also revealed more robust relationships between leukocyte measures and cardiometabolic risk markers in men than in women.Conclusion: This study provides novel data suggesting a significant association between neutrophil count and OSA severity only in men but not women. Similarly, the relationship between leukocyte parameters and cardiometabolic risk markers were more pronounced in men than women. Our findings suggest a sex-specific impact of OSA on leukocyte measures and on their relationship with indices of cardiometabolic risk.Keywords: obstructive sleep apnea, leukocyte measures, neutrophil, sex differences, cardiometabolic risk factors

Chengzhang Yang,1,2,* Weifang Liu,2,3,* Zijia Tong,1,* Fang Lei,3,4 Lijin Lin,2,3 Xuewei Huang,3,5 Xingyuan Zhang,3,6 Tao Sun,2,3 Gang Wu,1 Huajing Shan,1 Shaoze Chen,1 Hongliang Li2,3 1Department of Cardiology, Huanggang Central Hospital, Huanggang, People’s Republic of China; 2Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 3Institute of Model Animal, Wuhan University, Wuhan, People’s Republic of China; 4Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 5Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 6School of Basic Medical Science, Wuhan University, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongliang Li, Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China, Tel/Fax +86-27-68759302, Email lihl@whu.edu.cn Shaoze Chen, Department of Cardiology, Huanggang Central Hospital, Huanggang, People’s Republic of China, Tel/Fax +86-713-8381191, Email chenshaoze@hgyy.org.cnAim: The evidence on the association between insulin resistance (IR) and the prevalence or incidence of cardiac dysfunction has been controversial, and the relationship between pre-diabetic IR and cardiac function is lacking. Large sample studies in the Chinese general population are urgently needed to explore the association between IR and the risk of left ventricular hypertrophy (LVH) and decreased left ventricular diastolic function with preserved ejection fraction (LVDFpEF).Methods: Based on a National Health Check-up database in China, we conducted a multicenter cross-sectional retrospective study in 344,420 individuals. Furthermore, at a single center, we performed two retrospective longitudinal studies encompassing 8270 and 5827 individuals to investigate the association between IR and the development of new-onset LVH and LVDFpEF, respectively. The median follow-up duration exceeded 2.5 years. The triglyceride and glucose (TyG) index, known for its high sensitivity in detecting IR, serves as a reliable alternative marker of IR. The logistic and cox proportional hazard regression models were used to determine the relationships.Results: In the cross-sectional study, IR showed a positive association with the prevalence of LVH and decreased LVDFpEF after adjusting for confounders. In the longitudinal cohort, IR was also correlated with the new onset of LVH and decreased LVDFpEF, with hazard ratios (HR) of 1.986 (95% CI: 1.307, 3.017) and 1.386 (95% CI: 1.167, 1.647) in the fourth quartile of TyG levels compared to the lowest quartile, respectively, after adjusting for confounders. The subgroup analysis in non-hypertensive or non-diabetic people and the sensitivity analysis in the population with homeostasis model assessment of insulin resistance (HOMA-IR) further verified the above-mentioned results.Conclusion: IR was associated with LVH and decreased LVDFpEF. Effective management of IR may prevent or delay the development of adverse LVH and decreased LVDFpEF.Keywords: insulin resistance, triglyceride and glucose index, left ventricular hypertrophy, left ventricular diastolic function

Xujun Feng, Yuan Shi, Ye Zhang, Fei Lei, Rong Ren, Xiangdong Tang Department of Respiratory and Critical Care Medicine, Sleep Medicine Center, Mental Health Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Rong Ren; Xiangdong Tang, Department of Respiratory and Critical Care Medicine, Sleep Medicine Center, Mental Health Center, West China Hospital, Sichuan University, Dian Xin Nan Jie 28#, Chengdu, 610041, People’s Republic of China, Tel +86-28-85422733, Email 498880651@qq.com; 2372564613@qq.comAbstract: Lungs experience frequent interactions with the external environment and have an abundant supply of blood; therefore, they are susceptible to invasion by pathogenic microorganisms and tumor cells. However, the limited pharmacokinetics of conventional drugs in the lungs poses a clinical challenge. The emergence of different nano-formulations has been facilitated by advancements in nanotechnology. Inhaled nanomedicines exhibit better targeting and prolonged therapeutic effects. Although nano-formulations have great potential, they still present several unknown risks. Herein, we review the (1) physiological anatomy of the lungs and their biological barriers, (2) pharmacokinetics and toxicology of nanomaterial formulations in the lungs; (3) current nanomaterials that can be applied to the respiratory system and related design strategies, and (4) current applications of inhaled nanomaterials in treating respiratory disorders, vaccine design, and imaging detection based on the characteristics of different nanomaterials. Finally, (5) we analyze and summarize the challenges and prospects of nanomaterials for respiratory disease applications. We believe that nanomaterials, particularly inhaled nano-formulations, have excellent prospects for application in respiratory diseases. However, we emphasize that the simultaneous toxic side effects of biological nanomaterials must be considered during the application of these emerging medicines. This study aims to offer comprehensive guidelines and valuable insights for conducting research on nanomaterials in the domain of the respiratory system. Keywords: nanoparticles, respiratory system, lungs, nanomaterials, nanotechnology

Xiao-Hui Song,1,&ast; Bo Liu,2,3,&ast; Fang Lei,2,4 Ye-Mao Liu,2,5,6 Xingyuan Zhang,2,4 Ze Chen,7 Peng Zhang,2,4 Xiao-Jing Zhang,2,4 Zhi-Gang She,1,2 Jingjing Cai,2,8 Jin-Hua Wang,9 Hongliang Li1– 3,6 1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Institute of Model Animal, Wuhan University, Wuhan, People’s Republic of China; 3Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 4School of Basic Medical Science, Wuhan University, Wuhan, People’s Republic of China; 5Department of Cardiology, Huanggang Central Hospital of Yangtze University, Huanggang, People’s Republic of China; 6Huanggang Institute of Translational Medicine, Huanggang Central Hospital of Yangtze University, Huanggang, People’s Republic of China; 7Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 8Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 9Department of Neurology, Huanggang Central Hospital of Yangtze University, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongliang Li, Department of Cardiology, Renmin Hospital of Wuhan University, Luojia Mount Wuchang, Wuhan, 430072, People’s Republic of China, Tel/Fax +86-27-68759302, Email lihl@whu.edu.cn Jin-Hua Wang, Department of Neurology, Huanggang Central Hospital of Yangtze University, Hubei, 438000, People’s Republic of China, Email wangjinhua1985@qq.comPurpose: Emerging evidence suggested that metabolic dysfunction-associated fatty liver disease (MAFLD) was significantly associated with atherosclerotic diseases. Atherosclerosis in the peripheral arteries is the most common cause of peripheral arterial disease (PAD), which has not been substantially controlled in the past. We aimed to investigate the association between MAFLD and PAD in the Chinese population.Patients and Methods: This observational study covered 102,115 participants who underwent health checkups with detailed examinations for PAD and MAFLD. PAD was measured by ankle-brachial index, and MAFLD was diagnosed by abdominal ultrasound. The generalized linear mixed models and random-effects Cox proportional hazards models were used to analyze the relationship between MAFLD and PAD.Results: The baseline characteristics showed that patients with MAFLD had higher prevalence of PAD compared with those without MAFLD (2.7% vs 2.2%). Compared to non-MAFLD, the individuals with MAFLD were associated with a higher risk of the presence of PAD (adjusted odds ratio: 1.30, 95% confidence interval (CI): 1.19– 1.42, P < 0.001). In the prospective cohort study, 6833 participants underwent a follow-up of 2.76 (standard deviation: 1.36) years, and MAFLD at baseline was a higher risk of associated with incident PAD (adjusted hazards ratio: 1.67, 95% CI: 1.17– 2.38, P = 0.005). Moreover, with the accumulation of metabolic abnormalities, the risk of the PAD was increased in the individuals with MAFLD. Furthermore, MAFLD attributed risk of PAD was more evident in participants without metabolic comorbidities.Conclusion: MAFLD was associated with a significantly higher risk for the prevalence and incidence of PAD in the Chinese population. The finding suggested that individuals with MAFLD are not only have a higher risk of coronary heart diseases but also have an increased risk of atherosclerosis in peripheral arteries.Keywords: chronic liver disease, metabolic disorder, arteriosclerosis, cross-sectional study, prospective cohort study

Lu Tan,1 Taomei Li,1 Lian Luo,1 Xiaofang Xue,2,3 Fei Lei,1 Rong Ren,1 Ye Zhang,1 Jiaming He,2,3 Konrad E Bloch,4 Xiangdong Tang1,5– 7 1Sleep Medicine Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Emergency, Diqing Tibetan Autonomous Prefectural People’s Hospital, Shangri-La, People’s Republic of China; 3Department of Intensive Care Unit, Diqing Tibetan Autonomous Prefectural People’s Hospital, Shangri-La, People’s Republic of China; 4Department of Respiratory Medicine, Sleep Disorders Center, University Hospital of Zurich, Zurich, Switzerland; 5Mental Health Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 7State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Xiangdong Tang, Sleep Medicine Center, Mental Health Center, Department of Respiratory and Critical Care Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 28 Dian Xin Nan Jie, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-28-85422733, Fax +86-28-85422632, Email 2372564613@qq.comPurpose: Obstructive sleep apnea (OSA) is common both at low and high altitude. Since adaptations to high altitude and respiratory control may differ among Tibetans and Hans, we compared characteristics of sleep-disordered breathing in the two ethnic groups at high altitude.Materials and Methods: This was a prospective observational study including 86 Tibetan and Han long-term (> 5 years) high altitude residents with chief complaints of snoring and/or witnessed apnea underwent clinical evaluation and polysomnography at 3200 meters in Shangri-La, China.Results: In 42 Tibetans, 38 men, median (quartiles) age was 50.0 (41.0; 56.0)y, total apnea/hypopnea index (AHI) 53.9 (32.0; 77.5)/h, obstructive AHI 51.0 (28.0; 72.2)/h and central AHI 1.5 (0.2; 3.1)/h. In 44 Hans, 32 men, median (quartiles) age was 47.0 (43.5; 51.0)y, total AHI 22.2 (12.8; 39.2)/h, obstructive AHI 17.7 (12.0; 33.0)/h and central AHI 2.4 (0.5; 3.4)/h (p < 0.001 total and obstructive AHI vs Tibetans). In Tibetans, mean nocturnal oxygen saturation was lower [median 85.0 (83.0; 88.0)% vs 88.5 (87.0; 90.0)%] and obstructive apnea and hypopnea duration was longer [22.0 (19.6; 24.8) sec vs 18.3 (16.7; 20.6) sec] than in Hans (all p < 0.001). In regression analysis, Tibetan ethnicity, neck circumference and high-altitude living duration were the predictors of total AHI. We also found that with every 10/h increase in total AHI, there were an approximately 0.9 beat/min and 0.8 beat/min increase in mean heart rate during rapid eye movement (REM) and non-REM sleep and 1.9 mmHg and 2.0 mmHg increase in evening and morning systolic blood pressure.Conclusion: Our data suggest that Tibetans presented more severe obstructive sleep apnea, hypoxemia and longer apnea duration compared to Hans at 3200 meters, which was correlated with higher heart rate and blood pressure suggesting a greater cardiovascular risk.Keywords: obstructive sleep apnea, high altitude, Tibetan, long-term Han resident

A carbothermal reduction process simulating EAF process is used to handle the zinc oxide dust, and the zinc in the dust can be extracted and recovered efficiently. The crude zinc and lead-tin alloy were obtained finally. The effects of temperature, holding time, and reductant dosage on zinc volatilization rate were investigated, and the “Pelletizing - Calcination- Carbothermic reduction” experiment was conducted. The results found the optimal reduction condition was as follows: the temperature of 1300℃, reductant dosage of 14.04%, and holding time of 120 min. After the calcination at 900℃ for 120 min, the removal rates of fluorine, chlorine, and sulfur in the dust were 98.18%, 96.38% and 28.58% respectively, and the volatilization rate of zinc was 99.83% in the reduction process. The zinc content of the crude zinc was 68.48%.

Shuanghong Luo,1,2 Chuncheng Wu,3 Qiuhong Luo,1,2 Mengdong Ran,4 Yin Liu,5 Fei Lei,6 Xin Chen,7 Zheng Yuan,8 Hanmin Liu,1,2 Chaomin Wan1,2 1Department of Paediatrics, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, People’s Republic of China; 3Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 4Department of Biostatistics, West China Women & Children Union Doctor, Chengdu, People’s Republic of China; 5Research and Development Department, West China Women & Children Union Doctor, Chengdu, People’s Republic of China; 6Medical Information Center, West China Women & Children Union Doctor, Chengdu, People’s Republic of China; 7Child Health Care Department, Nanxin Community Health Service Center, High-Tech Zone, Chengdu, People’s Republic of China; 8Economics School, Southwestern University of Finance and Economics, Chengdu, People’s Republic of ChinaCorrespondence: Chaomin Wan Tel/Fax +86-28-85503185Email wanchaomin@scu.edu.cnAbstract: As an implementation strategy, the actual functional scope of clinical pathway (CPW) can be mastered is the basis for evaluating and improving CPW management, which is very important for bridging the evidence-to-practice gap. Here, we propose and discuss a design and evaluation model for CPWs through some theoretical lenses that may help the designer master the actual functional scope of CPWs and accumulate and refine effective key management steps of a specific disease. We can thus determine the best-optimized design with the largest net benefit that allows definition of the core management steps for a specific disease.Keywords: implementation science, clinical pathway, evidence-based medicine, health technology assessment, public health economics

Xiao Tang,1 Hongya Zhang,1 Yanxiang Zhao,2 Fang Lei,1 Qigui Liu,1 Dongmei Hu,1 Guorong Li,1 Guirong Song1 1Department of Health Statistics, School of Public Health, Dalian Medical University, Dalian City, Liaoning Province, 116044, People’s Republic of China; 2Department of Mathematics, George Washington University, Washington, DC, USACorrespondence: Guirong SongDepartment of Health Statistics, School of Public Health, Dalian Medical University, No. 9 South Road, Lvshun District, Dalian City, Liaoning Province, 116044, People’s Republic of ChinaTel +86-411-86110328Email songsara110@163.comBackground: Obesity is well recognized as a risk factor for cardiometabolic diseases. The development of obesity is a dynamic process that can be described as a multistate process with an emphasis on transitions between weight states. However, it is still unclear what convenient biomarkers predict transitions between weight states. The aim of this study was to show the dynamic nature of weight status in adults stratified by age and sex and to explore blood markers of metabolic syndrome (MetS) that predict transitions between weight states.Methods: This study involved 9795 individuals aged 18 to 56 at study entry who underwent at least two health check-ups in the eight-year period of study in the health check-up centre of our institution. Weight, height and biochemical indices were measured at each check-up. The participants were divided into four groups based on age and sex (young male, middle-aged male, young female and middle-aged female groups). A multistate Markov model containing 3 states (healthy weight, overweight and obesity) was adopted to study the longitudinal weight data.Results: Young people were more likely to transit between weight states than middle-aged people, and middle-aged people were more resistant to recover from worse states. The mean sojourn time in obesity was greatest in the middle-aged male group (6.23 years), and the predicted rate of obesity beginning with healthy weight was greatest in the young male group (13.7%). In multivariate models, age group and triglyceride (TG) and high-density lipoprotein cholesterol (HDL) levels were significant for specific transitions in females, whereas age group and HDL levels were significant in males. In females, if HDL levels increased 1 mmol/L, the probability of progression from healthy weight to overweight decreased by 37.0% (HR= 0.63), and the probabilities of recovery (overweight to healthy weight and obesity to overweight) increased by 62.0% (HR= 1.62) and 1.23-fold (HR= 2.23), respectively. In males, if TG levels increased 1 mmol/L, the risk of progression from healthy weight to overweight increased by 24.0% (HR= 1.24). Each unit increase in HDL levels was associated with a 0.99-fold (HR= 1.99) increase in the chance of recovery from overweight to healthy weight and with a 0.37-fold (HR= 0.63) decrease in the risk of progression from healthy weight to overweight.Conclusion: The weight status of young people was less stable than that of middle-aged people. Males were more likely to become overweight and more resistant to recover from worse states than females. Young males with healthy weight were more likely to develop obesity than other healthy weight groups. Blood lipid levels, especially HDL, were predictors of weight transitions in adults. Prevention and intervention measures should be applied early.Keywords: obesity, multistate Markov model, triglyceride, high-density lipoprotein cholesterol, low density lipoprotein cholesterol

Xueting Wang,1,2 Xuejiao Li,2 XuHui Liu,3 Yizhe Yin,1 Yalong Dang,2 Fang Lei1 1Department of Ophthalmology, Henan University of Science and Technology School of Medicine, Luoyang, Henan, 471000, People’s Republic of China; 2Sanmenxia Central Hospital, Henan University of Science and Technology, Sanmenxia, Henan, 472000, People’s Republic of China; 3Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of ChinaCorrespondence: Yalong Dang; Fang Lei Tel +86-398-3118149; +86-379-64231886Email dangyalong@haust.edu.cn; leifang@haust.edu.cnAbstract: A 31-year-old male with mild dizziness complained of cloudy vision in his right eye for 5 days. The visual acuity of both eyes was normal, while the visual contrast sensitivity of both eyes slightly reduced. Fundus examination showed the swollen and radial superficial hemorrhage of his both optic nerves. Brain MRI scan indicated a huge tumor in the right temporal lobe with clear boundary, close to the skull. The midline structure shifted to the left. Blood tests indicated no hyperlipidemia or lipid disorders. The patient then received tumor resection. The size of the tumor was 5.6 cm × 7.5 cm × 10.1 cm. Histology suggested many foam cell accumulations and the tumor was positive for CD34, CD99, Vimentin, β-Catenin and CD68, but negative for EMA, GFAP, IDH-1, Oliga-2, PR, S-100, and CD1a. Three months after surgery, MRI showed the midline structure was back to normal. The swollen and radial superficial hemorrhage of optic nerves had disappeared. The visual acuity and visual field remained normal.Keywords: intracranial xanthoma, optic nerve, visual function, neurological disorder, optic disc edema

Tongtong Zhou,1,* Yaozhong Wang,2,* Fengcai Lei,3 Jing Yu4 1Collaborative Innovation Center for Nanomaterials & Devices, College of Physics, Qingdao University, Qingdao 266071, People’s Republic of China; 2Department of Oral and Maxillo-Facial Surgery, Qingdao Stomatological Hospital, Qingdao, People’s Republic of China; 3College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan, People’s Republic of China; 4School of Physics and Electronics, Shandong Normal University, Jinan 250014, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fengcai Lei; Jing Yu Email fengcai9213@126.com; yujing1608@126.comIntroduction: During routine surgery, rapid hemostasis, especially the rapid hemostasis of internal organs, is very important. The emergence of in-situ electrospinning technology has fundamentally solved this problem. It exhibits a high speed of hemostasis, and no bleeding occurs after surgery. Thus, it is of great significance. The use of sutures in some human organs, such as the intestines and bladder, is inadequate because fluid leakage occurs due to the presence of pinholes.Methods: Three types of large intestine wounds with an opening of about 1 cm were investigated. They were untreated, treated by needle and threaded, and treated by hand-held electrospinning, respectively.Results: The results show that hand-held electrospinning technique effectively prevented the exudation of fluids in the intestinal tract. The average diameter of the nanofibrous membrane was about 0.5 μm with hole of several micrometers. It can be elongated 90% without breakage. The hand-held electrospinning device could be used with nitrile gloves, preventing the risk of infection caused by exposed hands.Discussion: This work can provide a reference for future animal experiments and clinical experiments. However, safety should be investigated before application.Keywords: electrospinning, hemostasis, nanofibers

Yun Du,1,2 Wentong Zhang,3 Feng Lei,4 Xia Yu,1 Zhuming Li,1 Xiaodong Liu,1 Yanan Ni,1 Li Deng,4 Mingfang Ji1 1Cancer Research Institute of Zhongshan City, Zhongshan City People’s Hospital, Zhongshan 528400, People’s Republic of China; 2Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Stockholm, Sweden; 3Department of Chinese Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 4Department of Radiotherapy, Zhongshan City People’s Hospital, Zhongshan, People’s Republic of ChinaCorrespondence: Mingfang JiCancer Research Institute of Zhongshan City, Zhongshan City People’s Hospital, No. 2. Sunwen Road East, Zhongshan 528400, Guangdong, People’s Republic of ChinaTel +86 135 3206 2222Fax +86 076488822698Email jmftbh@sina.comPurpose: NPC is a malignant and invasive tumor with the incidence rate of 19/100,000 per year in Zhongshan City, a prefecture city in southern China. Long-term survival analysis on intensity-modulated radiotherapy (IMRT)-based treatment in local prefecture-level hospitals have not been investigated. We aimed to evaluate the 5-year clinical outcomes and prognostic factors of NPC treated with IMRT in Zhongshan City People’s Hospital (ZSPH), a prefecture-level hospital in South China.Patients and Methods: The number of 149 newly diagnosed non-metastatic NPC cases treated with IMRT were included from Zhongshan City People’s Hospital between January 2010 and December 2011. The survival outcomes, treatment toxicities and prognostic factors were analyzed by Kaplan-Meier method and Cox proportional hazards model.Results: With a median follow-up period of 65 months for the cohort, the 5-year local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS) and distant metastasis-free survival (DMFS) and overall survival (OS) were 86.80%, 94.80%, 86.10% and 80.50%, respectively. The 5-year OS rates were 100%, 95.2%, 87% and 67.2% for stage I, II, II and IVa-b, respectively (P=0.004). The 5-year LRFS rates were 97.2%, 96.0%, 90.4% and 72.0% for T1, T2, T3 and T4, respectively (P=0.001); the 5-year DMFS rates were 100% for T1, 96.8% for T2, 81.9% for T3 and 74.6% for T4 (P=0.022). A multivariate analysis revealed tumor stage as an independent prognostic factor for LRFS, DMFS and OS. No patients died from acute toxicities. Late toxicities were observed for 130 (87.2%) patients, and most late toxicities were graded I/II.Conclusion: NPC treatment effect in a prefecture-level hospital in South China was comparable to international results and toxicities were tolerable. Tumour stage was an independent prognostic factor for survival outcome. More NPC survival data from local and remote places are needed.Keywords: nasopharyngeal carcinoma, intensity-modulated, radiotherapy, prognosis, long-term survival results

An image processing algorithm for detecting individual weeds was developed and evaluated. Weed detection processes included were normalized excessive green conversion, statistical threshold value estimation, adaptive image segmentation, median filter, morphological feature calculation and Artificial Neural Network (ANN). The developed algorithm was validated for its ability to identify and detect weeds and crop plants under uncontrolled outdoor illuminations. A machine vision implementing field robot captured field images under outdoor illuminations and the image processing algorithm automatically processed them without manual adjustment. The errors of the algorithm, when processing 666 field images, ranged from 2.1 to 2.9%. The ANN correctly detected 72.6% of crop plants from the identified plants, and considered the rest as weeds. However, the ANN identification rates for crop plants were improved up to 95.1% by addressing the error sources in the algorithm. The developed weed detection and image processing algorithm provides a novel method to identify plants against soil background under the uncontrolled outdoor illuminations, and to differentiate weeds from crop plants. Thus, the proposed new machine vision and processing algorithm may be useful for outdoor applications including plant specific direct applications (PSDA).

AniMAIRE (Anisotropic Model for Atmospheric Ionising Radiation Effects) is a new model and Python toolkit for calculating radiation dose rates experienced by aircraft during anisotropic solar energetic particle events. AniMAIRE expands the physics of the MAIRE + model such that dose rate calculations can be performed for anisotropic solar energetic particle conditions by supplying a proton or alpha particle rigidity spectrum, a pitch angle distribution, and the conditions of Earth's magnetosphere. In this paper, we describe the algorithm and top‐level structure of AniMAIRE and showcase AniMAIRE's capabilities by analyzing the dose rate maps that AniMAIRE produces when the time‐dependent spectra and pitch angle distribution for Ground Level Enhancement (GLE) 71 are input. We find that the dose rates AniMAIRE produces for the event fall between the dose rates produced by the WASAVIES and CRAC:DOMO models. Dose rate maps that evolve throughout the event are also shown, and it is found that each peak in the input pitch angle distribution generates a dose rate hotspot in each of the polar regions. AniMAIRE has been made available openly online so that it can be downloaded and run freely on local machines and so that the space weather community can easily contribute to it using Github forking. Plain Language Summary: Solar particle events occur when particles are accelerated in eruptions on the Sun. If these particles hit Earth and have enough energy, they can penetrate Earth's magnetosphere and atmosphere, creating radiation showers that increase the radiation in Earth's atmosphere. When such increases are detected by neutron monitors at sea level, they are known as Ground‐Level Enhancements (GLEs), which occur once a year on average. GLEs can cause issues in aircraft electronics and cause passengers and crew on airplanes to experience heightened radiation doses. In this paper, we describe a new model to calculate radiation dose rates in the atmosphere during GLEs, called AniMAIRE. Most models that exist to date are only able to calculate radiation dose rates when all particles are hitting Earth equally from all directions, however this approximation is only reliable during the later stages of events, and isn't accurate for many GLEs. AniMAIRE has been designed so it doesn't need to rely on this approximation, and can calculate dose rates for situations where it is supplied a direction‐dependent particle flux, as well as those independent of direction. AniMAIRE has been tested across a GLE in May 2012, showing the direction dependent approach is necessary. Key Points: AniMAIRE can simulate atmospheric radiation and electronics effects from anyinput anisotropic distribution of particles hitting EarthAnisotropy is important in the event‐integrated dose calculation for GLE71 according to AniMAIREAniMAIRE has been made openly available online, such that anyone can run and experiment with it, or contribute to the model through forking [ABSTRACT FROM AUTHOR]

This paper describes the second data release (DR2) of the Beijing-Arizona Sky Survey (BASS). BASS is an imaging survey covering a 5400 deg2 footprint in the g and r bands using the 2.3 m Bok telescope. DR2 includes the observations through 2017 July obtained by BASS and by the Mayall z-band Legacy Survey (MzLS), which used the 4 m Mayall telescope to observe the same footprint. BASS and MzLS have completed 72% and 76% of their observations. The two surveys will be served for the spectroscopic targeting of the upcoming Dark Energy Spectroscopic Instrument. Both BASS and MzLS data are reduced by the same pipeline. We have updated the basic data reduction and photometric calibrations in DR2. In particular, source detections are performed on stacked images, and photometric measurements are co-added from single-epoch images based on these sources. The median 5σ point-source depths after Galactic extinction corrections are 24.05, 23.61, and 23.10 mag for the g, r, and z bands, respectively. The DR2 data products include stacked images, co-added catalogs, and single-epoch images and catalogs. The BASS website (http://batc.bao.ac.cn/BASS/) provides detailed information and links to download the data.

Long non-coding RNAs (lncRNAs) have a critical role in cancer initiation and progression, and thus may mediate oncogenic or tumor suppressing effects, as well as be a new class of cancer therapeutic targets. We performed high-throughput sequencing of RNA (RNA-seq) to investigate the expression level of lncRNAs and protein-coding genes in 30 esophageal samples, comprised of 15 esophageal squamous cell carcinoma (ESCC) samples and their 15 paired non-tumor tissues. We further developed an integrative bioinformatics method, denoted URW-LPE, to identify key functional lncRNAs that regulate expression of downstream protein-coding genes in ESCC. A number of known onco-lncRNA and many putative novel ones were effectively identified by URW-LPE. Importantly, we identified lncRNA625 as a novel regulator of ESCC cell proliferation, invasion and migration. ESCC patients with high lncRNA625 expression had significantly shorter survival time than those with low expression. LncRNA625 also showed specific prognostic value for patients with metastatic ESCC. Finally, we identified E1A-binding protein p300 (EP300) as a downstream executor of lncRNA625-induced transcriptional responses. These findings establish a catalog of novel cancer-associated functional lncRNAs, which will promote our understanding of lncRNA-mediated regulation in this malignancy.

Abstract Overexpression of mitotic arrest deficiency 2 (MAD2/MAD2L1), a pivotal component of the spindle assembly checkpoint (SAC), resulted in many types of cancer. Here we show that the depletion of tumor susceptibility gene 101 (TSG101), causes synthetic dosage lethality (SDL) in MAD2-overexpressing cells, and we term this cell death MAD2-overexpressing interphase cell death (MOID). The induction of MOID depends on PML and DAXX mediating mitochondrial AIFM1-release. MAD2, TSG101, and AIF-PML-DAXX axis regulate mitochondria, PML nuclear bodies (NBs), and autophagy with close inter-dependent protein stability in survival cells. Loss of C-terminal phosphorylation(s) of TSG101 and closed (C-)MAD2-overexpression contribute to induce MOID. In survival cells, both MAD2 and TSG101 localize at PML NBs in interphase, and TSG101 Y390 phosphorylation is required for localization of TSG101 to PML NBs. PML release from PML NBs through PML deSUMOylation contributes to induce MOID. The post-transcriptional/translational cell death machinery and the non-canonical transcriptional regulation are intricately linked to MOID, and ER-MAM, may serve as a crucial intersection for MOID signaling.

Abstract Isoliquiritigenin (ISL), a naturally occurring flavonoid derived from licorice root, exhibits antioxidant, anticancer, anti-inflammatory, and anti-allergic properties, and is frequently detected in both environmental and human samples. Previous studies from our lab have demonstrated that ISL exposure can lead to developmental deformities and aberrant immune responses. However, the molecular mechanisms underlying ISL toxicity in zebrafish embryos remain incompletely elucidated. Therefore, this study aimed to elucidate the effects of ISL exposure on endoplasmic reticulum (ER) stress in zebrafish embryos by assessing the expression levels of ER stress markers HSPA5 and CHOP, along with associated apoptosis factors, under various ISL concentrations, with tunicamycin (TM) serving as a positive control. Furthermore, targeted analyses of ER stress-related pathways were conducted using RNA transcriptome sequencing, and the up-regulated gene was verified by western blot. The results revealed that ISL exposure significantly elevated the expression levels of HSPA5 and CHOP, concomitantly activating ER stress pathways, including pPERK-eIF2α-ATF4 and ATF6 pathways in zebrafish embryos. These findings suggest that the activation of endoplasmic reticulum stress signaling pathways may contribute to the developmental deformities observed in zebrafish embryos following ISL exposure, thereby highlighting the potential ecological risks associated with ISL usage.

Abstract Accurately identifying periodontal landmarks via acoustic imaging is increasingly important. Here, we evaluated the accuracy of cementoenamel junction (CEJ) identification using ultrasound by comparing it to clinical methods in 153 extracted human teeth. The distance between the CEJ to a reference point was measured using two clinical methods (visual examination and tactile sensation) as well as ultrasound imaging. Statistical analyses were performed across all teeth and sub-groups, including tooth types (incisors, cuspids, and molars/premolars), and two classifications: A- vs. B- (visually detectable or undetectable CEJ, respectively); and CL-S vs. CL-D (shallow or deep cervical lesions). In A- or CL-S teeth, ultrasound measurements highly agreed with clinical measurements, showing a 1.72-mm 95% CI for A- and 1.99-mm 95% CI for CL-S compared to visual examination, and a 1.77-mm 95% CI for A- and a 2.10-mm 95% CI for CL-S compared to tactile sensation, respectively. For 80% of A- and 76% of CL-S teeth, the difference between ultrasound and visual examination was within ± 20%. For 81% of A- and 80% of CL-S teeth, the difference between ultrasound and tactile sensation was within ± 20%. The variance of ultrasound versus clinical CEJ identifications showed a significant correlation (r = 0.6607) to the cervical lesion depth. The errors between ultrasound and clinical measurements show no significant bias across different tooth types.

Abstract Plasmids, as important genetic elements apart from chromosomes, often carry multiple resistance genes and various mobile genetic elements, enabling them to acquire more exogenous genes and confer additional resistance phenotypes to bacteria. Various carbapenem resistance genes are often located on IncN plasmids, and several reports have linked fusion plasmids to IncN plasmids. Therefore, this study aims to explore the emergence, molecular structure characteristics, and resistance features mediated by IncN fusion plasmids carrying multiple carbapenem resistance genes. In this study, species identification was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS). Polymerase chain reaction (PCR) was employed to detect the presence of carbapenem resistance genes in the strains. PCR-based replicon typing (PBRT) was used to identify IncN plasmids. Plasmids were analyzed through S1-nuclease pulsed-field gel electrophoresis (S1-PFGE), Southern blotting, conjugation experiments, and stability tests. Whole-genome sequencing (WGS) and antimicrobial susceptibility testing (AST) were conducted to characterize the target strains. Four strains containing IncN plasmids were identified: two Klebsiella pneumoniae, one Escherichia coli, and one Enterobacter cloacae, all harboring carbapenem resistance genes. Among them, two IncN plasmids (pFAHZZU7605-KPC-IMP and pFAHZZU7865-IMP) contained blaIMP−4 and exhibited similar molecular structure characteristics. Notably, the pFAHZZU7605-KPC-IMP plasmid harbored both IncN and IncR replicons. We hypothesize that the pFAHZZU7605-KPC-IMP fusion plasmid resulted from the recombination of a pFAHZZU7865-IMP-like plasmid and an IncR-like plasmid. Further analysis of the plasmid’s genetic elements revealed that insertion sequences ISKpn19 and ISKpn27 played crucial roles in the plasmid recombination and fusion process. In clinical settings, plasmids carrying different resistance genes can undergo fusion, mediated by genetic elements, thereby expanding the resistance spectrum of host bacteria. Hence, it is essential to enhance the monitoring and research of transposable elements to control the spread of multidrug-resistant bacteria.

Abstract The increasing prevalence of carbapenem-resistant Enterobacter cloacae complex (CREC) poses great challenges to infection treatment in the clinical setting. In this study, we reported the emergence of carbapenemase in a rare species, Enterobacter chuandaensis, belonging to the Enterobacter cloacae complex (ECC). We elucidated the genetic characteristics of carbapenem-resistant isolate FAHZZU5885, co-harboring bla NDM−1 and bla KPC−2. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and average nucleotide identity (ANI) analysis were used to identify E. chuandaensis. S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) and Southern blotting were used to clarify the number and size of the plasmids in FAHZZU5885. Antimicrobial phenotypes were identified by antimicrobial susceptibility testing (AST), and the characteristics of the strain were examined with whole-genome sequencing (WGS). The conjugation experiment and stability assay were conducted to verify the transferability and stability of the plasmid carrying carbapenemase-encoding genes. E. chuandaensis FAHZZU5885 was isolated from a perianal swab of a patient admitted to the ICU. This strain simultaneously carried bla NDM−1 and two bla KPC−2 genes. FAHZZU5885 was resistant to most of the tested antibiotics except for amikacin, tigecycline, and colistin. Two bla KPC−2 were located separately on two different plasmids, the ~ 120 kb IncFIA-IncFII plasmid and the ~ 80 kb IncR plasmid. Both plasmids shared the conserved sequence klcA-korC-ISkpn6-bla KPC−2 -ISkpn27-tnpR-tnpA. The bla NDM−1-bearing plasmid had the potential to transfer and can remain stable after successive passages. In addition, the bla NDM−1 was carried on a ~ 80 kb IncFII plasmid with the conserved sequence ISAba125-bla NDM−1-ble-trpF-dsbD-cutA-groS-groL. In summary, this study marks the first report of the multidrug-resistant E. chuandaensis strain FAHZZU5885 harboring two bla KPC−2-bearing plasmids, indicating the potential for the further dissemination of carbapenemase-encoding genes in novel species. The findings contribute to enhancing our understanding of CREC strains, emphasizing the need for continued and comprehensive surveillance of this species.

Abstract Background Skin cutaneous melanoma (SKCM) poses a significant public health challenge due to its aggressive nature and limited treatment options. To address this, the study introduces the Tumor Mutational Burden-Derived Immune lncRNA Prognostic Index (TILPI) as a potential prognostic tool for SKCM. Methods TILPI was developed using a combination of gene set variation analysis, differential expression analysis, and COX regression analysis. Additionally, functional experiments were conducted to validate the findings, focusing on the effects of STARD4-AS1 knockdown on SKCM tumor cell behavior. These experiments encompassed assessments of tumor cell proliferation, gene and protein expression, migration, invasion, and in vivo tumor growth. Results The results demonstrated that knockdown of STARD4-AS1 led to a significant reduction in tumor cell proliferation and impaired migration and invasion abilities. Moreover, it resulted in the downregulation of ADCY4, PRKACA, and SOX10 gene expression, as well as decreased protein expression of ADCY4, PRKACA, and SOX10. In vivo experiments further confirmed the efficacy of STARD4-AS1 knockdown in reducing tumor growth. Conclusions This study elucidates the mechanistic role of STARD4-AS1 and its downstream targets in SKCM progression, highlighting the importance of the ADCY4/PRKACA/SOX10 pathway. The integration of computational analysis with experimental validation enhances the understanding of TILPI and its clinical implications. Overall, the findings underscore the potential of novel computational frameworks like TILPI in predicting and managing SKCM, particularly through targeting the ADCY4/PRKACA/SOX10 pathway.

Abstract Background Drought stress is a significant abiotic stressor that hinders growth, development, and crop yield in soybeans. Strigolactones (SLs) positively regulate plant resistance to drought stress. However, the impact of foliar application of SLs having different concentrations on soybean growth and metabolic pathways related to osmoregulation remains unknown. Therefore, to clarify the impact of SLs on soybean root growth and cellular osmoregulation under drought stress, we initially identified optimal concentrations and assessed key leaf and root indices. Furthermore, we conducted transcriptomic and metabolic analyses to identify differential metabolites and up-regulated genes. Results The results demonstrated that drought stress had a significant impact on soybean biomass, root length, root surface area, water content and photosynthetic parameters. However, when SLs were applied through foliar application at appropriate concentrations, the accumulation of ABA and soluble protein increased, which enhanced drought tolerance of soybean seedlings by regulating osmotic balance, protecting membrane integrity, photosynthesis and activating ROS scavenging system. This also led to an increase in soybean root length, lateral root number and root surface area. Furthermore, the effects of different concentrations of SLs on soybean leaves and roots were found to be time-sensitive. However, the application of 0.5 µM SLs had the greatest beneficial impact on soybean growth and root morphogenesis under drought stress. A total of 368 differential metabolites were screened in drought and drought plus SLs treatments. The up-regulated genes were mainly involved in nitrogen compound utilization, and the down-regulated metabolic pathways were mainly involved in maintaining cellular osmoregulation and antioxidant defenses. Conclusions SLs enhance osmoregulation in soybean plants under drought stress by regulating key metabolic pathways including Arachidonic acid metabolism, Glycerophospholipid metabolism, Linoleic acid metabolism, and Flavone and flavonol biosynthesis. This study contributes to the theoretical understanding of improving soybean adaptability and survival in response to drought stress.

In order to reduce the risk of coal mine production, timely predict and control the risk of roadway roof fall, twelve evaluation indexes such as the thickness of stable rock strata, geological conditions and cross-section shape of roadway were selected. The risk evaluation index system of roadway roof fall was constructed, and the risk degree standard of roadway roof fall was proposed. The risk evaluation model of roadway roof fall was established by using the combination weight matter-element extension theory of analytic hierarchy process (AHP) and entropy weight (EW). The risk degree of roadway roof fall was determined according to the principle of maximum membership degree, and the risk assessment system of roadway roof fall (MW-MEW) was developed based on JavaWeb. The evaluation method and MW-MEW system were applied to evaluate the risk degree of roof fall in C9 return air connecting roadway of Xinglu Coal Mine, and the evaluation results were compared with those of AHP-matter element extension model. The results showed that the evaluation results of the evaluation method were in line with the actual engineering situation and were better than the AHP-matter element extension model.

Abstract This study investigated how resting-state functional connectivity (rsFC) of the subgenual anterior cingulate cortex (sgACC) predicts antidepressant response in patients with major depressive disorder (MDD). Eighty-seven medication-free MDD patients underwent baseline resting-state functional MRI scans. After 12 weeks of escitalopram treatment, patients were classified into remission depression (RD, n = 42) and nonremission depression (NRD, n = 45) groups. We conducted two analyses: a voxel-wise rsFC analysis using sgACC as a seed to identify group differences, and a prediction model based on the sgACC rsFC map to predict treatment efficacy. Haufe transformation was used to interpret the predictive rsFC features. The RD group showed significantly higher rsFC between the sgACC and regions in the fronto-parietal network (FPN), including the bilateral dorsolateral prefrontal cortex (DLPFC) and bilateral inferior parietal lobule (IPL), compared to the NRD group. These sgACC rsFC measures correlated positively with symptom improvement. Baseline sgACC rsFC also significantly predicted treatment response after 12 weeks, with a mean accuracy of 72.64% (p

Abstract Suicidal ideation (SI) is a significant precursor and risk marker for suicide behaviors in major depressive disorder (MDD). Exploration of SI trajectory from a longitudinal framework are essential for treatment guidelines and clinical management of suicide risk. This study sought to explore SI trajectories and its associated clinical, sociodemographic characteristics, and initial treatment among patients with MDD. We used data from a non-interventional, national multi-centered prospective cohort study. 1 461 patients with MDD were included in the growth mixture modeling using SI at baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks, and 6 months, 9 months, and 12 months as the indicator. A multinomial regression was employed with SI trajectory as the outcome and anhedonia, depressive symptoms, atypical depressive symptoms, pharmacological treatments, and other covariates as the predictors. Four distinct SI trajectories were identified: a consistently low SI trajectory(50.7%), a persistently mild SI trajectory(20.6%), a fast declined SI trajectory(8.9%), and a slowly declined trajectory(19.8%). Compared to those with a consistently low SI trajectory, a higher score of anhedonia was associated with an increased risk of experiencing persistently mild (RRR = 1.20, 95%CI: 1.05, 1.38) and slowly declined SI (1.54, 95%CI: 1.32, 1.80). Severity of depressive symptom was also positively associated with the risk of experiencing persistently mild (1.15, 95%CI: 1.13, 1.18) and slowly declined SI (1.17, 95%CI: 1.14, 1.21). And the risk of experiencing slowly declined SI was higher for those use SSRI(1.49, 95%CI: 1.02, 2.31), and for those use antidepressant and antipsychotic/mood stabilizer combined therapy (3.78, 95%CI: 1.48, 9.61). The findings of this study are potentially useful for clinical practice as critical indicators of profiles and interventions for prognosis among patients with MDD. Further research is warranted to explore potential modifiable factors and the association between SI trajectories and suicide behavior.

This study involved the ultrasonic modification of water-soluble pectin, chelator-soluble pectin, and sodium carbonate-soluble pectin in blueberries using different ultrasonic treatments (688, 1376, 2063 W/cm2, 10, 20, 30 min). The research explored the relationship between the modified pectin structure and the interaction between pectin and cyanidin-3-O-glucoside (C3G). The results showed that ultrasonic modification resulted in enhanced interaction between pectin and C3G. After the ultrasonic treatment of 2063 W/cm2 for 10 min, all three pectins showed the maximum binding capacity with C3G, which was about 2~6 times higher than that without the ultrasonic modification. Whereas, prolonged ultrasonic time (20~30 min) was unfavorable for the interaction between modified pectin and C3G. After ultrasonic modification, the particle size of the pectin-C3G complexes became smaller, the Zeta potential was increased, and the physical stability was thus improved. In three different pectin samples, ultrasonic treatment induced a reduction in molecular weight and methyl esterification of the pectin, facilitated the degradation of the branched structures, promoted the number of free carboxyl groups, and increased the presence of structural network voids. The alteration of the structural properties of pectin by ultrasonic treatment facilitated the interactions between pectin and C3G.

Pectin is a major constituent of the plant cell wall. Pectate lyase (PEL, EC 4.2.2.2) uses anti-β-elimination chemistry to cleave the α-1,4 glycosidic linkage in the homogalacturonan region of pectin. However, limited information is available on the comprehensive and evolutionary analysis of PELs in the Malvaceae. In this study, we identified 597 PEL genes from 10 Malvaceae species. Phylogenetic and motif analyses revealed that these PELs are classified into six subfamilies: Clades I, II, III, IV, Va, and Vb. The two largest subfamilies, Clades I and II, contained 237 and 222 PEL members, respectively. The members of Clades Va and Vb only contained four or five motifs, far fewer than the other subfamilies. Gene duplication analysis showed that segmental duplication played a crucial role in the expansion of the PEL gene family in Gossypium species. The PELs from Clades I, IV, Va, and Vb were expressed during the fiber elongation stage, but nearly all PEL genes from Clades II and III showed no expression in any of the investigated fiber developmental stages. We further performed single-gene haplotype association analysis in 2,001 G. hirsutum accessions and 229 G. barbadense accessions. Interestingly, 14 PELs were significantly associated with fiber length and strength traits in G. barbadense with superior fiber quality, while only eight GhPEL genes were found to be significantly associated with fiber quality traits in G. hirsutum. Our findings provide important information for further evolutionary and functional research on the PEL gene family members and their potential use for fiber quality improvement in cotton.

Abstract To solve the problem of controlling large deformation of surrounding rock in deep soft rock roadway, the distribution characteristics and deformation mechanism of surrounding rock cracks in soft rock roadway under different lateral pressure coefficients are studied using numerical simulation, theoretical analysis, and field measurement. The results show that under different lateral pressure coefficients, the range of surrounding rock cracks shows three forms: round, oval, and butterfly. No matter what lateral pressure coefficient the roadway is in, the surrounding rock cracks always appear in the plastic zone, and there is a high correlation between the surrounding rock crack range and the plastic zone. The stress characteristics of the surrounding rock in the plastic zone include two main aspects. One is that the direction of the principal stress of the surrounding rock is deflected, which is manifested as an annular distribution of the direction of the maximum principal stress around the roadway. The direction of the minimum principal stress in the upper part of the roadway points to the center of the roadway, and the direction of the minimum principal stress in the lower part of the roadway deviates from the center of the roadway. Second, the ratio of the maximum to minimum principal stress in the surrounding rock is large. Under this stress characteristic, the surrounding rock in the plastic zone has strong shear dilation. The shear dilation makes the crack of the surrounding rock open so that the surrounding rock is squeezed into the roadway space, and then the roadway produces large deformation. Due to the large range of cracks in the butterfly‐shaped plastic zone, the shear dilation deformation produced by the butterfly‐shaped plastic zone is far more than that of the round/oval plastic zone. According to the crack range of roadway surrounding rock under different lateral pressure coefficients, the corresponding support scheme is put forward. Field experiments show that the support scheme can effectively control the deformation of surrounding rock and meet the requirements of roadway use.

In September 2014, Shanxi Earthquake Agency and the Institute of Geophysics, China Earthquake Administration jointly completed the construction of the geomagnetic station array in the Hengshan fault zone in the north of Shanxi. The geomagnetic station array is composed of 5 GM4 type fluxgate magnetometers, which are respectively installed in Daixian, Shanyin, Yingxian, Fanchi and Huairen to obtain the three-component magnetic field data in the observation area. The 5 measurement points of the geomagnetic station array are located near the grounding electrode of the Jinnan line of high-voltage direct current transmission. By comparing the GM4 type fluxgate magnetometer at the 5 measurement points of the geomagnetic station array with the geomagnetic second data of other stations, the interference amplitude of the high-voltage direct current transmission line (Jinbei-Nanjing) on the geomagnetic data of the Shanxi geomagnetic station array was measured, correlation and error analysis also were carried out, and the fitting formula was obtained. The results show that the variation amplitude of the Z component disturbed by the Jinnan line high-voltage direct current transmission in the Shanxi geomagnetic station array decreases as the vertical distance from the station location to the Jinnan line increases, and the interference amplitudes of the H and D components are linearly correlated with the interference amplitude of the Z component. Taking the variation of the Z component as the dependent variable, using the reference fitting formula to obtain the variation of the H and D components can be applied to the daily processing work of the magnetic field interference of the Shanxi geomagnetic station array under the influence of the Jinnan line high-voltage direct current transmission.

Abstract Background Chimeric antigen receptor (CAR)-T therapy has emerged as a promising treatment for hematologic malignancies. However, cytopenia remains one of the most frequent and challenging adverse effects of this therapy. Methods We conducted a retrospective analysis of 26 patients with relapsed/refractory aggressive B-cell lymphoma who received CAR-T therapy at our center. Subsequently, to investigate measures to address cytopenias following CAR-T therapy, we isolated and generated murine CAR-T cells and bone marrow-derived mesenchymal stem cells (MSCs), establishing a murine syngeneic CAR-T therapy model. We assessed the impact of MSC infusion on hematopoietic recovery post-CAR-T therapy by evaluating complete blood count, bone marrow hematopoietic stem cells and their subpopulations, bone marrow histomorphology, and hematopoiesis-related genes. Results All patients experienced cytopenias to varying degrees, with complete lineage involvement in half of the patients. Grade ≥ 3 cytopenias were observed in 88.46% of the patients. CAR-T therapy was associated with a higher incidence of biphasic, late-onset, or prolonged cytopenias. Survival analysis indicated that neutropenia and lymphopenia tended to be associated with better prognosis, whereas thrombocytopenia tended to be related to poorer outcomes. Through animal experiments, we discovered that MSCs infusion boosted HSCs and their long-term subpopulations, enhancing hematopoietic recovery, particularly in the megakaryocyte lineage, and mitigating bone marrow damage. Importantly, both in vitro and in vivo experiments demonstrated that MSCs did not compromise the activity or antitumor efficacy of CAR-T cells. Conclusions Our findings propose MSCs infusion as a promising strategy to address cytopenias, particularly thrombocytopenia, after CAR-T therapy. This approach could help overcome certain limitations of cellular immunotherapy by enhancing hematopoietic recovery without compromising the efficacy of CAR-T cells. Highlights 1 Cytopenia is a frequently observed adverse effect following CAR-T therapy, and it is often characterized by biphasic and prolonged patterns. 2 MSCs play a critical role in promoting hematopoietic recovery and mitigating bone marrow damage in a murine model of CAR-T therapy 3 The activity and antitumor efficacy of CAR-T cells were not impaired by MSCs. Graphical Abstract

Abstract While rapid demographic changes in Asia are driving the incidence of chronic aging-related diseases, the limited availability of high-quality in vivo data hampers our ability to understand complex multi-factorial contributions, including gut microbial, to healthy aging. Leveraging a well-phenotyped cohort of community-living octogenarians in Singapore, we used deep shotgun-metagenomic sequencing for high-resolution taxonomic and functional characterization of their gut microbiomes (n = 234). Joint species-level analysis with other Asian cohorts identified distinct age-associated shifts characterized by reduction in microbial richness, and specific Alistipes and Bacteroides species enrichment (e.g., Alistipes shahii and Bacteroides xylanisolvens). Functional analysis confirmed these changes correspond to metabolic potential expansion in aging towards alternate pathways synthesizing and utilizing amino-acid precursors, vis-à-vis dominant microbial guilds producing butyrate in gut from pyruvate (e.g., Faecalibacterium prausnitzii, Roseburia inulinivorans). Extending these observations to key clinical markers helped identify >10 robust microbial associations to inflammation, cardiometabolic and liver health, including potential probiotic species (e.g., Parabacteroides goldsteinii) and pathobionts (e.g., Klebsiella pneumoniae), highlighting the microbiome’s role as biomarkers and potential targets for promoting healthy aging.

Hemophilic articular cartilage damage presents a significant challenge for surgeons, characterized by recurrent intraarticular bleeding, a severe inflammatory microenvironment, and limited self-repair capability of cartilage tissue. Currently, there is a lack of tissue engineering-based integrated therapies that address both early hemostasis, anti-inflammation, and long-lasting chondrogenesis for hemophilic articular cartilage defects. Herein, we developed an adhesive hydrogel using oxidized chondroitin sulfate and gelatin, loaded with exosomes derived from bone marrow stem cells (BMSCs) (Hydrogel-Exos). This hydrogel demonstrated favorable injectability, self-healing, biocompatibility, biodegradability, swelling, frictional and mechanical properties, providing a comprehensive approach to treating hemophilic articular cartilage defects. The adhesive hydrogel, featuring dynamic Schiff base bonds and hydrogen bonds, exhibited excellent wet tissue adhesiveness and hemostatic properties. In a pig model, the hydrogel could be smoothly injected into the knee joint cartilage defect site and gelled in situ under fluid-irrigated arthroscopic conditions. Our in vitro and in vivo experiments confirmed that the sustained release of exosomes yielded anti-inflammatory effects by modulating macrophage M2 polarization through the NF-κB pathway. This immunoregulatory effect, coupled with the extracellular matrix components provided by the adhesive hydrogel, enhanced chondrogenesis, promoted the cartilage repair and joint function restoration after hemophilic articular cartilage defects. In conclusion, our results highlight the significant application potential of Hydrogel-Exos for early hemostasis, immunoregulation, and long-term chondrogenesis in hemophilic patients with cartilage injuries. This innovative approach is well-suited for application during arthroscopic procedures, offering a promising solution for addressing the complex challenges associated with hemophilic articular cartilage damage.

Small cell lung cancer (SCLC), one of the histological subtypes of lung cancer, is characterized by high proliferation, early metastasis, susceptibility to drug resistance and recurrence. For several years, SCLC has always been regarded as a homogeneous disease, treated with a unified radiotherapy and chemotherapy strategy. Despite significant early therapeutic effects, drug resistance and recurrence occur quickly, and there is a lack of satisfactory treatment results, which may be due to insufficient understanding of the tumor heterogeneity of SCLC at present. Recently, the concept of SCLC molecular subtype based on the definition of relatively high expression of lineage transcription factors has been proposed in preclinical studies. This article mainly elaborates on the current status and latest findings of SCLC molecular subtype, emphasizing the potential problems that molecular typing may encounter in clinical practice, aiming to promote understanding of the research progress of molecular subtype in SCLC.

Abundance sensitivity is an important technical index of magnetic mass spectrometer, which describes the extent to which the tailing of intense ion peaks at a mass number in its neighborhood affects the weak ion peaks during isotope ratio measurement. It is particularly important in the measurement of isotope ratios containing low abundance nuclides, such as 234U/238U, 236U/238U, and 230Th/232Th. However, the abundance sensitivity of magnetic mass spectrometer is only of the order of 10−6 without taking additional technical measures. To further improve the abundance sensitivity, the techniques of tandem mass spectrometer, such as magnetic-electric, magnetic-magnetic and magnetic-electric-quadrupole tandem mass spectrometer, and retarding filter can be adopted. In fact, while various tandem mass spectrometer techniques can effectively improve the abundance sensitivity of an instrument, they also significantly increase the size, complexity, and cost of instrument, and therefore are not widely used. In contrast, due to its simple structure, small size, and excellent performance, the retarding filter has become a key component for commercial magnetic mass spectrometers to improve abundance sensitivity. Based on the basic principles of ion optics, a retarding filter consisting of five electrodes with a compact structure of only (40×50×50) mm3 was developed by utilizing the ion optics simulation software SIMION8.1. In addition to the function of energy retarding, the retarding filter also has the function of direction retarding, which greatly enhances the filtering capability to scatter ions. To test the ion transmission efficiency and the abundance sensitivity under different voltages, the retarding filter was installed on a domestic double-focusing thermal ionization mass spectrometer (TIMS). The instrument mainly consists of a thermal ionization source, a double focusing mass analyzer consisting of an electrostatic analyzer and a magnetic mass analyzer, a zoom lens, and a multi-collector detector, which can be configured with up to 16 faraday cups, 4 electron multipliers, and 2 retarding filters. The results showed that the abundance sensitivity of the mass spectrometer is successfully improved from

Abstract Non-direct antimicrobial cationic peptides (NDACPs) are components of the animal innate immune system. But their functions and association with antimicrobial peptides (AMPs) are incompletely understood. Here, we reveal a synergistic interaction between the AMP AW1 and the NDACP AW2, which are co-expressed in the frog Amolops wuyiensis. AW2 enhances the antibacterial activity of AW1 both in vitro and in vivo, while mitigating the development of bacterial resistance and eradicating biofilms. AW1 and AW2 synergistically damage bacterial membranes, facilitating cellular uptake and interaction of AW2 with the intracellular target bacterial genomic DNA. Simultaneously, they trigger the generation of ROS in bacteria, contributing to cell death upon reaching a threshold level. Moreover, we demonstrate that this synergistic antibacterial effect between AMPs and NDACPs is prevalent across diverse animal species. These findings unveil a robust and previously unknown correlation between AMPs and NDACPs as a widespread antibacterial immune defense strategy in animals.

This is an article in the field of analytical testing. As a green and environmentally friendly fire gold test method for efficient separation and enrichment of trace precious metals in ore, bismuth gold test effectively avoids the problem of toxic pollution of lead test gold. In this article, Bi2O3 with low toxicity is used as the fire test gold trap of Au element, and Bi2O3 is reduced to Bi by the reducing agent flour in the test ingredient during the high-temperature melting process, and Au2Bi alloy is formed with Au in the samples, and the Ag protective ash blowing method is used to make Au and Ag form about 1mg of Ag zygote. The Ag zygoteum is heated and dissolved by acid solution method to completely enter the solution of Au. In this test, the Au element content in the national standard material GBW 07205 was used as a reference, and the effective pixels of the CCD detector of the continuous light source flame atomic absorption spectrometer were optimized, and 7 were selected as the effective pixels of the CCD detector based on their sensitivity and stability. In the mass concentration range of 0～20 μg/mL, the corresponding absorbance was fitted by the quadratic equation least squares method, the fitting coefficient of the calibration curve was 0.999 8, the characteristic concentration was 0.069 97 μg/mL, and the detection limit of the method was 0.012 7 g/mL. According to the selected experimental method and optimized instrument parameters, Au in the national standard material was determined, and the measured value was in good agreement with the standard value, and the relative standard deviation (RSD, n=6) was 2.23%～4.54%. The established method was applied to the test of Au in actual ore samples, and the recovery rate of spiked was 92.6%～106%. The relative standard deviation (n=6) was 2.53%～4.70%, which met the requirements of the National Geological and Mineral Resources Industry Standard DZ/T 0130-2006.

Abstract Neurons rely heavily on high mitochondrial metabolism to provide sufficient energy for proper development. However, it remains unclear how neurons maintain high oxidative phosphorylation (OXPHOS) during development. Mitophagy plays a pivotal role in maintaining mitochondrial quality and quantity. We herein describe that G protein-coupled receptor 50 (GPR50) is a novel mitophagy receptor, which harbors the LC3-interacting region (LIR) and is required in mitophagy under stress conditions. Although it does not localize in mitochondria under normal culturing conditions, GPR50 is recruited to the depolarized mitochondrial membrane upon mitophagy stress, which marks the mitochondrial portion and recruits the assembling autophagosomes, eventually facilitating the mitochondrial fragments to be engulfed by the autophagosomes. Mutations Δ502-505 and T532A attenuate GPR50-mediated mitophagy by disrupting the binding of GPR50 to LC3 and the mitochondrial recruitment of GPR50. Deficiency of GPR50 causes the accumulation of damaged mitochondria and disrupts OXPHOS, resulting in insufficient ATP production and excessive ROS generation, eventually impairing neuronal development. GPR50-deficient mice exhibit impaired social recognition, which is rescued by prenatal treatment with mitoQ, a mitochondrially antioxidant. The present study identifies GPR50 as a novel mitophagy receptor that is required to maintain mitochondrial OXPHOS in developing neurons.

Abstract Background The traumatic spinal cord injury (SCI) can cause immediate multi-faceted function loss or paralysis. Microglia, as one of tissue resident macrophages, has been reported to play a critical role in regulating inflammation response during SCI processes. And transplantation with M2 microglia into SCI mice promotes recovery of motor function. However, the M2 microglia can be easily re-educated and changed their phenotype due to the stimuli of tissue microenvironment. This study aimed to find a way to maintain the function of M2 microglia, which could exert an anti-inflammatory and pro-repair role, and further promote the repair of spinal cord injury. Methods To establish a standard murine spinal cord clip compression model using Dumont tying forceps. Using FACS, to sort microglia from C57BL/6 mice or CX3CR1GFP mice, and further culture them in vitro with different macrophage polarized medium. Also, to isolate primary microglia using density gradient centrifugation with the neonatal mice. To transfect miR-145a-5p into M2 microglia by Lipofectamine2000, and inject miR-145a-5p modified M2 microglia into the lesion sites of spinal cord for cell transplanted therapy. To evaluate the recovery of motor function in SCI mice through behavior analysis, immunofluorescence or histochemistry staining, Western blot and qRT-PCR detection. Application of reporter assay and molecular biology experiments to reveal the mechanism of miR-145a-5p modified M2 microglia therapy on SCI mice. Results With in vitro experiments, we found that miR-145a-5p was highly expressed in M2 microglia, and miR-145a-5p overexpression could suppress M1 while promote M2 microglia polarization. And then delivery of miR-145a-5p overexpressed M2 microglia into the injured spinal cord area significantly accelerated locomotive recovery as well as prevented glia scar formation and neuron damage in mice, which was even better than M2 microglia transplantation. Further mechanisms showed that overexpressed miR-145a-5p in microglia inhibited the inflammatory response and maintained M2 macrophage phenotype by targeting TLR4/NF-κB signaling. Conclusions These findings indicate that transplantation of miR-145a-5p modified M2 microglia has more therapeutic potential for SCI than M2 microglia transplantation from epigenetic perspective. Graphical Abstract

Abstract Connected and autonomous driving technologies offer a novel solution for intersection control optimization. Connected and autonomous vehicles (CAVs) can access signal plans and optimize trajectories to minimize delays and reduce fuel consumption. However, optimizing trajectories for individual vehicles significantly increases complexity, especially for joint optimization of traffic signals and vehicle trajectories. Given the current technical, regulatory, and policy constraints, a superior intersection management approach is necessary before fully automated driving is achieved. This paper introduces an adaptive coupling control (ACC) method based on vehicle platooning to optimize signal timings and vehicle trajectories in mixed traffic. Initially, vehicle platoon segmentation is conducted, led by CAVs. The study then proposes a single‐layer coupled optimization model based on vehicle platoons, simplifying the joint optimization model. To address logistic constraint difficulties, a linearization of the coupled model (LCM) method is developed. Numerical experiments demonstrate that the ACC method significantly reduces vehicle delay and fuel consumption. At high CAV penetration rates (0.8 < R

Abstract The mislocalization of proteins leads to breast cancer, one of the world’s most prevalent cancers, which can be identified from immunohistochemical images. Here, based on the deep learning framework, location prediction models were constructed using the features of breast immunohistochemical images. Ultimately, six differentially localized proteins that with stable differentially predictive localization, maximum localization differences, and whose predicted results are not affected by removing a single image are obtained (CCNT1, NSUN5, PRPF4, RECQL4, UTP6, ZNF500). Further verification reveals that these proteins are not differentially expressed, but are closely associated with breast cancer and have great classification performance. Potential mechanism analysis shows that their co-expressed or co-located proteins and RNAs may affect their localization, leading to changes in interactions and functions that further causes breast cancer. They have the potential to help shed light on the molecular mechanisms of breast cancer and provide assistance for its early diagnosis and treatment.

The failure of butterfly plastic zone in roadway surrounding rock is an important reason for the large deformation of roadway surrounding rock. In recent years, it has attracted the attention of roadway support workers. The understanding on the deformation mechanism of surrounding rock in the butterfly plastic zone is the basis for realizing the control of surrounding rock in soft rock roadway. However, there are limited studies on the deformation mechanism of surrounding rock in the butterfly failure theory. In view of the above problems, the large deformation characteristics of the south transport roadway in a mine in the southern China are taken as the research object. Based on the analysis of the stress environment and geological conditions of the roadway, the distribution of surrounding rock cracks, the deformation mechanism and control methods of the roadway are systematically studied. The results show that the south transport roadway is a typical extremely unequal pressure soft rock roadway. After the excavation of the roadway, the surrounding rock cracks are distributed in a ‘butterfly’ shape. The ‘butterfly fracture zone’ is concentrated in the ‘butterfly plastic zone’. The fractures of the surrounding rock at the butterfly leaf are mainly shear fractures, and the shear fractures at the butterfly leaf are mostly distributed around the roadway in a ‘ring’ distribution, while the tensile fractures are concentrated near the free surface of the surrounding rock of the roadway. There are two main aspects of the stress characteristics of the surrounding rock in the butterfly plastic zone. One is the deflection of the principal stress direction of the surrounding rock, which is manifested in the annular distribution of the maximum principal stress around the roadway. The direction of the minimum principal stress in the upper part of the roadway points to the center of the roadway, and the direction of the minimum principal stress in the lower part of the roadway deviates from the center of the roadway. The second is that the maximum / minimum principal stress ratio of the surrounding rock is large, and the principal stress ratio contour is ‘butterfly’ distributed. According to the distribution characteristics and stress characteristics of surrounding rock cracks in plastic zone, the mechanical dilatancy model of surrounding rock with weak surface is established. It is considered that the dilatancy effect of surrounding rock under this stress characteristic is strong, and the dilatancy effect makes the surrounding rock squeeze into the roadway space, which makes the roadway produce large deformation. The irregular distribution of surrounding rock fissures and the unreasonable original support scheme are the main reasons for the large deformation of the roadway. The study mentioned above is used to suggest a differentiated support system, the heart of which is ‘full-section prestressed short anchor cable + key part long anchor cable strengthening support + grouting’. Field observation demonstrates that the revised support plan can successfully manage the surrounding rock’s deformation and guarantee the stability of the roadway while it is in operation.