Search

Qizhi Diao,1 Yongpei Long,2 Fangyu Yang,3 Cuihui Nong,1 Huamiao Tang,1 Xiangmin Zhou,1 Guoqiang Zhu,4 Qiang Ding5 1Hainan Branch, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Sanya, People’s Republic of China; 2Department of Laboratory Medicine, The People’s Hospital of Jianyang City, Sichuan, People’s Republic of China; 3Department of Clinical Laboratory Medicine, University-Town Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Chong Qing King Med Center for Clinical Laboratory Co., Ltd, Chongqing, People’s Republic of China; 5The Sixth People’s Hospital of Chongqing, Chongqing, People’s Republic of ChinaCorrespondence: Guoqiang Zhu; Qiang Ding, Email Guoqiangzhu01@163.com; yung10167086@126.comBackground and Objective: Inadequate risk assessment and a lack of risk monitoring are common deficiencies in clinical laboratory, and are also the main causes of biosafety incidents. Therefore, we summarized the experience of implementing adequate risk assessment and maintaining risk monitoring, and established a procedure for continuously improving biosafety management.Methods: Learning from our laboratory’s experience in implementing risk assessment, risk response, and risk monitoring before and during the COVID-19 epidemic, we summarized the procedures for fully identifying risks, accurately evaluating risks, maintaining risk monitoring, establishing and regular reviewing safety indicators. On this basis, we established a system for continuously improving biosafety management through risk monitoring and reviewing safety indicator.Results: We identified a total of 30 unacceptable risks prior to the COVID-19 pandemic, and developed and implemented appropriate risk control measures. After risk control, residual risks were acceptable, and no biosafety incidents have occurred. During the COVID-19 pandemic, after multiple risk monitoring, we identified ten new risks, three ineffective risk control measures, and multiple control measures for excessive protection. Then, we timely adjusted risk control measures to avoid laboratory personnel infection and excessive protection. Meanwhile, We established eight safety indicators and identified two improvement opportunities through regular reviews.Conclusion: Adequate risk identification and accurate risk assessment are particularly important for effectively controlling biosafety risks. Biosafety management should be continuously improved to deal with ineffective and excessive protection caused by various changes in experimental activities. Continuous improvement of biosafety management can be achieved through risk monitoring, regular review of safety indicators, and management reviews. This study will help laboratory managers to fully and accurately assess risks, as well as update risks and their control measures through risk monitoring, and the continuous improvement procedure established in the study has certain reference value for laboratories to effectively respond to emerging infectious diseases and avoid excessive protection.Keywords: risk assessment, risk monitoring, management review, continuous improvement, biosafety management

Liming Qin,1,2,&ast; Moqin Qiu,3,&ast; Jingmei Tang,2 Shuyan Liu,4 Qiuling Lin,5 Qiongguang Huang,2 Xiaoxia Wei,5 Qiuping Wen,1 Peiqin Chen,6 Zihan Zhou,7 Ji Cao,7 Xiumei Liang,8 Qian Guo,9 Cunli Nong,9 Yizhen Gong,5 Yuying Wei,1 Yanji Jiang,10 Hongping Yu,1,2,11– 13 Yingchun Liu1 1Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2School of Public Health, Guangxi Medical University, Nanning, People’s Republic of China; 3Department of Respiratory Oncology, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 4Key Laboratory of Biological Molecular Medicine Research, Education Department of Guangxi Zhuang Autonomous Region, Guangxi Medical University, Nanning, People’s Republic of China; 5Department of Clinical Research, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 6Editorial Department of Chinese Journal of Oncology Prevention and Treatment, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 7Department of Cancer Prevention and Control, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 8Department of Disease Process Management, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 9Liuzhou Worker’s Hospital, Liuzhou, People’s Republic of China; 10Department of Scientific Research, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 11Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of Education, Guangxi Medical University, Nanning, People’s Republic of China; 12Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, People’s Republic of China; 13Key Cultivated Laboratory of Cancer Molecular Medicine of Guangxi Health Commission, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingchun Liu; Hongping Yu, Department of Experimental Research, Guangxi Medical University Cancer Hospital, 71&num; Hedi Road, Qingxiu District, Nanning, People’s Republic of China, Tel +86-15877191237 ; +86-771-5330850, Fax +86-771-5312000, Email liuyingchun@stu.gxmu.edu.cn; yuhongping@stu.gxmu.edu.cnPurpose: P53 is a suppressor gene closely related to carcinogenesis. However, the associations between genetic variants in the p53 signaling pathway and prognosis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remain unknown. The current study aims to analyze associations between the single nucleotide polymorphisms (SNPs) in p53 pathway-related genes and survival of patients with HBV-HCC.Methods: We evaluated the associations between 4698 SNPs in 70 genes of the p53 pathway and overall survival (OS) of 866 patients in additive genetic models by using Cox proportional hazards regression analysis. Stepwise multivariable Cox regression analysis was conducted to determine the independent effects of identified SNPs in single-locus analyses. The expression of quantitative trait loci (eQTL) was also analyzed using data from GTEx and 1000 Genomes Project, and functional prediction of SNPs was performed by using RegulomeDB v2.2, 3DSNP v2.0, HaploReg v4.2 and VannoPortal.Results: We found that two novel SNPs of CD82 rs7925603 A > G and PMAIP1 rs4396625 A > T, were significantly and independently associated with OS [adjusted hazards ratios (HRs) and 95% confidence intervals (CI) were 1.27 (1.10– 1.48) and 0.77 (0.66– 0.91), respectively; P = 0.001 and = 0.002, respectively] and that the combined risk genotypes of these SNPs showed a significant association with OS in patients with HBV-HCC (Ptrend < 0.001). Further eQTL analysis in the GTEx dataset showed that the rs7925603 G allele was associated with lower CD82 mRNA expression levels, while the rs4396625 T allele was associated with higher PMAIP1 mRNA expression levels in whole blood cells.Conclusion: We identified two observed survival-associated SNPs in CD82 and PMAIP1 in the p53 pathway, which influenced HBV-HCC survival possibly through a mechanism of altering mRNA expression. Large studies are warranted to validate our findings.Keywords: hepatocellular carcinoma, hepatitis B virus, p53 signaling pathway, genetic variants, survival

Jiansheng Cai,1,2,&ast; Shuzhen Liu,1,&ast; You Li,3,&ast; Qiumei Liu,1 Min Xu,1 Chunbao Mo,3 Tingyu Mai,3 Xia Xu,1 Xu Tang,1 Quanhui Chen,1 Chuntao Nong,1 Huaxiang Lu,1,3 Haoyu He,1,4 Jiexia Tang,5 Junling Zhang,1 Chunmei Wei,1 Dechan Tan,3 Jian Qin,1 Zhiyong Zhang1,3 1Department of Environmental and Occupational Health, School of Public Health, Guangxi Medical University, Nanning, 530021, Guangxi Province, People’s Republic of China; 2Guangxi Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, People’s Republic of China; 3Department of Environmental Health and Occupational Medicine, School of Public Health, Guilin Medical University, Guilin, People’s Republic of China; 4Quality Management Department, the Affiliated Hospital of Stomatology, Guangxi Medical University, Nanning, People’s Republic of China; 5Guangxi Center for Disease Prevention and Control, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Qin; Zhiyong ZhangDepartment of Environmental and Occupational Health, School of Public Health, Guangxi Medical University, Shuangyong Road No. 22, Nanning, 530021, Guangxi Province, People’s Republic of ChinaTel +86-771-5358124Fax +86-771-5358124Email qinjian@gxmu.edu.cn; rpazz@163.comBackground: Animal experiments have found that oil tea reduces body weight and improves blood lipid levels. However, the effect of oil tea on human health has not been confirmed yet. This study aims to explore the relationship between oil tea consumption and obesity and dyslipidemia.Methods: In a cross-sectional population study in Guangxi, China, a semi-quantitative questionnaire was used to investigate the oil tea consumed and food consumption frequency in adults aged 30 years and over. Anthropometric variables and serum biochemical indicators were measured. A total of 2001 adults were divided into five groups based on their non-consumption status and quartile of consumption (groups non-drink oil tea, Q1–Q4).Results: The risk of abdominal obesity tended to decrease significantly with increasing consumption of oil tea (P for trend< 0.05) in the overall participants (Q3 group, OR = 0.545, 95% CI = 0.336– 0.884; Q4 group, OR = 0.520, 95% CI = 0.311– 0.871) and in women (Q2 group, OR = 0.502, 95% CI = 0.274– 0.920; Q3 group, OR = 0.397, 95% CI = 0.213– 0.740; Q4 group, OR = 0.421, 95% CI = 0.228– 0.780). Oil tea consumption Q1, Q2, Q3 and Q4 group significantly reduced the risk of abnormal HDL-cholesterol (P < 0.05). Oil tea consumption Q2 group significantly increased the risk of abnormal LDL-cholesterol (OR = 2.600, 95% CI = 1.033– 6.546) in women. Oil tea consumption Q1 (OR = 0.081, 95% CI =0.008– 0.864) and Q3 (OR = 0.057, 95% CI = 0.004– 0.913) groups significantly reduced the risk of abnormal HDL-cholesterol in women.Conclusion: Oil tea consumption may be associated with a low risk of abdominal obesity. High-dose oil tea consumption may be associated with a low risk of abnormal HDL-cholesterol. Prospective studies with large sample sizes would be required to further investigate this association.Keywords: abdominal obesity, blood lipid, HDL-C

Integrating vectors such as viruses and transposons insert transgenes semi-randomly and can potentially disrupt or deregulate genes. For these techniques to be of therapeutic value, a method for controlling the precise location of insertion is required. The piggyBac (PB) transposase is an efficient gene transfer vector active in a variety of cell types and proven to be amenable to modification. Here we present the design and validation of chimeric PB proteins fused to the Gal4 DNA binding domain with the ability to target transgenes to pre-determined sites. Upstream activating sequence (UAS) Gal4 recognition sites harbored on recipient plasmids were preferentially targeted by the chimeric Gal4-PB transposase in human cells. To analyze the ability of these PB fusion proteins to target chromosomal locations, UAS sites were randomly integrated throughout the genome using the Sleeping Beauty transposon. Both N- and C-terminal Gal4-PB fusion proteins but not native PB were capable of targeting transposition nearby these introduced sites. A genome-wide integration analysis revealed the ability of our fusion constructs to bias 24% of integrations near endogenous Gal4 recognition sequences. This work provides a powerful approach to enhance the properties of the PB system for applications such as genetic engineering and gene therapy.

The initial section of the Arctic Northeast Passage is located in the Yellow Sea and Bohai Sea of China. The severe weather types that may threaten the safety of shipping in this area are mainly strong winds and heavy precipitation. Among them the cold air gale accompanied by the cold wave process, as well as the disastrous weather such as strong wind and heavy precipitation caused by weather systems such as tropical cyclones and extratropical cyclones, have a great impact on shipping safety in this area. Based on the National Centers for Environmental Prediction (NCEP) global daily reanalysis data from 1991 to 2020, we analyze the energy propagation characteristics of the Rossby wave along the upper-level jet stream during the seaworthiness period (July to October) of the Arctic Northeast Passage and its impact on the weather in the initial section of the Arctic Northeast Passage, especially on heavy precipitation. The results are as follows. (1) The meridional wind along the 250 hPa westerly jet axis in the subtropical region of the Northern Hemisphere shows a zonal three-wave quasi-stationary Rossby wave pattern. (2) The atmospheric quasi-stationary Rossby wave source at 250 hPa is located in the Mediterranean region. The wave is excited here and propagates eastward along the jet stream. Although the wave energy is dissipated during the propagation process, continuous input of energy from the Mediterranean region maintains and strengthens the wave. (3) The absolute value of the correlation coefficient between the key area of the wave action flux divergence and the precipitation and wind speed in the initial section of the Arctic Northeast Passage is greater than 0.5. While the absolute value of the correlation coefficient between the key area wave action flux index and the precipitation and wind speed is close to 0.9, indicating a strong correlation, it shows that the energy of the Rossby wave is concentrated and strengthened when it propagates along the upper jet stream, significantly influencing the precipitation and wind speed in the initial section of the Northeast Passage of the Arctic, thus triggering disastrous weather such as heavy precipitation and strong winds. (4) When the Rossby wave disturbance is stronger, the downstream propagation energy is also stronger. The westerly jet is then strengthened, and the vertical upward motion is enhanced. This results in an abnormal increase in precipitation in the initial section of the Arctic Northeast Passage.

Abstract Background Displaced femoral neck fractures are associated with a high revision rate. The new femoral neck system(FNS) offers advantages in fixation stability, potentially reducing the need for revision. The purpose of this study was to compare the revision rate of patients with different reduction quality treated with the FNS and cannulated screws (CS). Methods This retrospective study included patients with Garden III or IV femoral neck fractures who underwent osteosynthesis in a level 1 trauma center between July 2019 and June 2023. A total of 141 cases met the inclusion criteria and received treatment with either the FNS (N = 65) or CS (N = 76). The quality of fracture reduction, surgical complications (such as femoral neck shortening, avascular necrosis of femoral head, nonunion of fracture, implant failure and withdrawal), revision surgery and the reasons for revision were analyzed. Results The mean age of the 141 cases was 52.0 years (range 18–65); with sixty-five cases being male (46.1%). Eighty-four fractures (59.6%) were classified as Garden type III. Reduction quality was good in 71 cases (50.4%) and fair in 70 cases. The mean follow-up period was 25.9 months (range 12–46). A total of 26 cases(18.4%) underwent revision surgery. The revision rate in cases with good reduction was 11.3% (8/71 cases), with seven cases (four hardware removal and three arthroplasty) in the CS group and one case (arthroplasty for fracture nonunion and implant failure) in the FNS group, a significant difference was found between the two groups(P = 0.041). Among the 18 cases (25.7%, 18/70) with fair reduction who underwent revision surgery, nine cases (six hardware removal and three arthroplasty) in the CS group, and nine cases (arthroplasty for implant failure and cut-out) in the FNS group, and there was no significant difference between the two groups (P = 0.672). The total revision rate between the FNS group (15.4%, 10/65) and the CS group (21.1%, 16/76) was not significantly different (P = 0.387). Conclusions The total revision rate between the FNS and CS group showed no difference. However, in cases with good reduction, the revision rate was lower in the FNS group compared to the CS group.

Abstract Background Open reduction and internal fixation were routinely used to treat patients with unstable ankle fractures (ORIF). However, some patients may experience persistent ankle pain and disability following ORIF due to untreated intra-articular lesions. Moreover, ankle fractures may be treated with arthroscopically assisted reduction and internal fixation (ARIF). This study aimed to compare the feasibility and benefits of ARIF versus ORIF for ankle fractures. Methods We performed this meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A systematic search was conducted for comparative studies comparing ARIF and ORIF for ankle fractures. Nine studies were included in the analysis of clinical and secondary outcomes. In summary, we calculated the mean difference (MD), risk ratio (RR), confidence interval, and p value. Results This meta-analysis demonstrated that the ARIF group achieved a higher Olerud–Molander Ankle (OMA) score (MD: 6.6; 95% CI 0.20 to 13.0; p = 0.04) and lower visual analog scale (VAS) score (MD: − 0.36; 95% CI − 0.64 to − 0.10; p = 0.01) at the final follow-up. Nevertheless, the smallest treatment effect of OMA score and VAS score did not exceed the minimum clinically important difference (MCID). There were longer surgery time (MD: 15.0; 95% CI 10.7 to 19.3; p

The regeneration potential of the mammalian heart is incredibly limited, as cardiomyocyte proliferation ceases shortly after birth. β-adrenergic receptor (β-AR) blockade has been shown to improve heart functions in response to injury; however, the underlying mechanisms remain poorly understood. Here, we inhibited β-AR signaling in the heart using metoprolol, a cardio-selective β blocker for β1-adrenergic receptor (β1-AR) to examine its role in heart maturation and regeneration in postnatal mice. We found that metoprolol enhanced cardiomyocyte proliferation and promoted cardiac regeneration post myocardial infarction, resulting in reduced scar formation and improved cardiac function. Moreover, the increased cardiomyocyte proliferation was also induced by the genetic deletion of Gnas, the gene encoding G protein alpha subunit (Gαs), a downstream effector of β-AR. Genome wide transcriptome analysis revealed that the Hippo-effector YAP, which is associated with immature cardiomyocyte proliferation, was upregulated in the cardiomyocytes of β-blocker treated and Gnas cKO hearts. Moreover, the increased YAP activity is modulated by RhoA signaling. Our pharmacological and genetic studies reveal that β1-AR-Gαs-YAP signaling axis is involved in regulating postnatal cardiomyocyte proliferation. These results suggest that inhibiting β-AR-Gαs signaling promotes the regenerative capacity and extends the cardiac regenerative window in juvenile mice by activating YAP-mediated transcriptional programs.

This paper uses the Long-range Energy Alternatives Planning(leap) system model to predict the carbon dioxide emissions of the power industry and calculate the carbon peak platform period of the power industry in Guangxi, which is based on the development status of the power industry and the energy and power development plan in Guangxi during the "14th Five-Year Plan". The results show that the power structure of Guangxi is at an excellent level in the country. In 2021, the installed proportion of clean energy is 55.1% (the national average level of 44.7% in 2020), and the proportion of thermal power generation is 55.7% (the national average level of 68.5% in 2020). With the strong economic recovery , the demand for electricity in Guangxi will continue to increase. By 2025 and 2030, the electricity consumption of the whole society will reach 2.9 ×1012 kW•h and 3.7×1012 kW•h, respectively, with an average annual growth rate of about 7.1% and 5.3%. The installed power generation capacity will reach 9.4 ×107 kW and 1.5 ×108 kW, respectively. The power generation will reach 3.0 ×1012 kW•h and 4.2×1012 kW•h electricity, respectively. However, Due to the influence of resource endowment, meteorological conditions, energy storage technology and other constraints on non-fossil energy power generation, it is difficult to achieve large-scale replacement of traditional energy power generation in a short term. It is estimated that coal power production will account for 45% and 30% of the total power generation respectively in Guangxi by 2025 and 2030. Coal power will continue to be the main provider of power security for a long time in the future. Therefore, according to the current situation of power development planning, it is estimated that the carbon emission of Guangxi will reach 9.2×107 t by 2030. The carbon peak platform period of power generation industry will appear in 2029 to 2032, with a peak value of 1.1 × 108 t.

Objective The number of patients with metastatic bone tumors of the pelvis (MBTP) has increased, and the risk of metastasis and recurrence in the pelvic bones is difficult to assess. Therefore, we investigated the clinical features and oncological outcomes of patients with MBTP. Methods We analyzed the clinical features and oncological outcomes of MBTP in 72 patients (42 men, 30 women; mean age, 50.5 years) from 2008 to 2017. Recurrence in the pelvic bones and survival rates were analyzed with regard to patients’ potential contributing factors. Results Enneking region I was the area most commonly containing MBTP (47.3%). Low- and high-grade tumors were identified in 40 and 32 patients, respectively. The most common pathological type was adenomatous carcinoma (34.7%), and the most common primary lesion was lung cancer (20.8%). The 3-year overall recurrence rate within the pelvic bones was 34.7%, and the 5-year overall survival rate was 29.2%. Conclusion Patients with MBTP have a high risk of recurrence in the pelvic bones and poor survival after multimodal treatment. Pelvic recurrence might be affected by the metastatic involvement, tumor grade, surgical margins, and type of surgery, whereas the survival rate tends to be associated with the tumor grade.

This paper presents a non-linear state observer-based integrated navigation scheme for estimating the attitude, position and velocity of micro aerial vehicles (MAV) operating in GPS-denied indoor environments, using the measurements from low-cost MEMS (micro electro-mechanical systems) inertial sensors and an RGB-D camera. A robust RGB-D visual odometry (VO) approach was developed to estimate the MAV’s relative motion by extracting and matching features captured by the RGB-D camera from the environment. The state observer of the RGB-D visual-aided inertial navigation was then designed based on the invariant observer theory for systems possessing symmetries. The motion estimates from the RGB-D VO were fused with inertial and magnetic measurements from the onboard MEMS sensors via the state observer, providing the MAV with accurate estimates of its full six degree-of-freedom states. Implementations on a quadrotor MAV and indoor flight test results demonstrate that the resulting state observer is effective in estimating the MAV’s states without relying on external navigation aids such as GPS. The properties of computational efficiency and simplicity in gain tuning make the proposed invariant observer-based navigation scheme appealing for actual MAV applications in indoor environments.

Salusin-α and salusin-β are newly found bioactive peptides of 28 and 20 amino acids, respectively, which are widely distributed in the hematopoietic system, endocrine system, and central nervous system. Salusins exert cardiovascular effects, including hypotension and bradycardia; promote vascular inflammation; and so on. However, little information is available yet on the relationships of salusin-β with sepsis. In this study, we investigated the distribution and content of endogenous salusin-β in septic rats. A total of 72 specified pathogen-free (SPF) male Sprague-Dawley (SD) rats were randomly divided into control group (sham operation, n = 36) and experimental group (n = 36) with sepsis rat model by cecal ligation and puncture (CLP). The model group rats were sacrificed after 6, 12, and 24 h of treatment. The concentration of salusin-β in spleen, stomach, small intestine, hypothalamus, and serum specimens was detected by enzyme-linked immunosorbent assay (ELISA). It showed that salusin-β was endogenously generated in rat tissues, including spleen, stomach, small intestine, hypothalamus, and serum. The content of salusin-β in the spleen was higher than that in other tissues. The content of salusin-β in the spleen, stomach, and small intestine, together with the serum level of salusin-β, increased significantly at 6 h after CLP compared with the control group ( P < 0.05). The content of salusin-β in spleen and serum peaked at 12 h, and in small intestine, it reached the summit at 24 h. Meanwhile, no significant fluctuations in salusin-β content were observed in the stomach. The content of salusin-β in hypothalamus began to increase at 6 h, and a significant increase appeared 12 h after CLP ( P < 0.05). In conclusion, this study shows that the time-dependent alterations of salusin-β in septic rats suggest that salusin-β might be involved in the pathogenesis of sepsis.

This paper presents a real-time motion planning approach for autonomous vehicles with complex dynamics and state uncertainty. The approach is motivated by the motion planning problem for autonomous vehicles navigating in GPS-denied dynamic environments, which involves non-linear and/or non-holonomic vehicle dynamics, incomplete state estimates, and constraints imposed by uncertain and cluttered environments. To address the above motion planning problem, we propose an extension of the closed-loop rapid belief trees, the closed-loop random belief trees (CL-RBT), which incorporates predictions of the position estimation uncertainty, using a factored form of the covariance provided by the Kalman filter-based estimator. The proposed motion planner operates by incrementally constructing a tree of dynamically feasible trajectories using the closed-loop prediction, while selecting candidate paths with low uncertainty using efficient covariance update and propagation. The algorithm can operate in real-time, continuously providing the controller with feasible paths for execution, enabling the vehicle to account for dynamic and uncertain environments. Simulation results demonstrate that the proposed approach can generate feasible trajectories that reduce the state estimation uncertainty, while handling complex vehicle dynamics and environment constraints.

Background and objective Advanced non-small cell lung cancer (NSCLC) is characterized by poor treatment efficacy and short survival time. Clinical trials have shown that the combination of chemotherapy with thermotherapy exhibits strong efficacy. We performed this meta-analysis to evaluate the clinical efficacy and safety of gemcitabine plus cisplatin (GP) and paclitaxel plus cisplatin (TP) combined with thermotherapy in the treatment of NSCLC, as well as to provide reference for clinical practice and future research. Methods We searched international (Cochrane Library, PubMed, and EMBASE) and Chinese (CBM, CNKI, VIP and Wanfang) databases for relevant articles and imported other retrievable sources, such as tracing-related references. We also corresponded with other authors to obtain certain inaccessible information. Data from all relevant randomized controlled trials (RCT) were collected to compare GP or TP thermochemotherapy with GP or TP chemotherapy alone. The quality of the included studies was assessed by adequate outcome-based standards and clinical circumstances. The meta-analysis was conducted using RevMan 5.1. Results Fifteen RCTs involving 952 patients were included in this meta-analysis. The results showed that the thermochemotherapy group had higher rates of improvement in quality of life (OR=3.84, 95%CI: 2.61-5.64), survival at 1 year (HR=1.94, 95%CI: 1.21-3.12), and survival at 2 years (HR=2.05, 95%CI: 1.18-3.58) compared with the chemotherapy group, with the differences between them being significant. However, these groups did not differ in other indicators of treatment effectiveness, such as myelosuppression, alimentary canal reactions, hepatic lesions, and diarrhea. Conclusion Compared with chemotherapy alone, thermochemotherapy can improve survival rates and curative effects, ameliorate symptoms, and enhance the quality of life of patients with advanced NSCLC, and it has an acceptable safety profile. The results of this meta-analysis warrant further investigation with a larger sample size and using a high-quality RCT design.

BACKGROUND: Hypoxia-inducible factor-1α (HIF-1α) plays an important role in tumour progression and metastasis through activation of many target genes that are especially involved in pivotal aspects of cancer biology. However, the prognostic role of HIF-1α has been controversial in primary patients with lung cancer. This meta-analysis was performed to systematically evaluate whether HIF-1α expression is associated with the clinical outcomes in lung cancer patients. METHODS: We retrieved relevant articles from Cochrane library, PubMed, EMbase, CNKI, CBM, VIP and Wan Fang Databases from inception to May 2012. Studies were selected using specific inclusion and exclusion criteria. A systematic review and meta-analysis was performed on the association between HIF-1α expression and clinical outcomes in lung cancer patients. All analyses were performed using the Revman 5.1 software. RESULTS: A total of 30 studies were identified as eligible for the systematic review and meta-analysis. The expression of HIF-1α was significantly higher than those in normal lung tissue; and III‒IV stage, lymph node metastasis, poorly differentiation, squamous cell carcinoma and small cell lung cancer (SCLC) were significantly higher than those in I‒II stage, no lymph node metastasis, well differentiation, adenocarcinomas and non small cell lung cancer (NSCLC), respectively (odds ratio (OR) = 19.00, 95% confidence interval (CI):12.12–29.78, p

Introduction: SARS-CoV-2 infection drove senescent cells and the senescence-associated phenotypes were reported playing roles in disease progression, which contributes to severe COVID-19 and related sequelae. Cdc42 is involved in the regulation of cellular senescence. This study, aimed to investigate the mechanism of the SARS-CoV-2 spike protein regulating cellular senescence through Cdc42., Methods: K18-hACE2 mice were infected with SARS-CoV-2 Omicron BA.4 or stimulated with spike protein through the airway, the senescent cells and Cdc42 expression in lung tissue were detected. Overexpression of spike protein or exogenous incubation of spike protein was used to simulate the induction of cellular senescence by spike protein. Mechanistic insights into the role of Cdc42 were mainly explored using Western Blot and qRT-PCR., Results: Spike protein, SARS-CoV-2 infection related, accelerates cell aging by upregulating Cdc42 expression, which furtherly activated the Wnt/β-catenin signaling pathway. Conversely, treatment with ML141 in animal models, a Cdc42 inhibitor, reduced cellular senescence and ameliorated lung injury and inflammation. These results suggest that the upregulation of Cdc42 by the SARS-CoV-2 spike protein induces cellular senescence and enhances β-catenin nuclear translocation., Discussion: This study provides insights into the mechanisms underlying cellular senescence induced by the SARS-CoV-2 spike protein, offering potential strategies to mitigate the inflammatory response and complications associated with COVID-19 in both the acute and long-term phases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nong, Wu, Yang, Xu, Luo, Zhou, Shen, Chen, Yuan and Hu.)

The development of rapidly distributed and retained probes within the kidneys is important for accurately diagnosing kidney diseases. Although molecular imaging shows the potential for non-intrusively interrogating kidney disease-related biomarkers, the limited kidney contrast of many fluorophores, owing to their relatively low distribution in the kidney, hinders their effectiveness for kidney disease detection. Herein, for the first time, an amino-functionalization strategy is proposed to construct a library of kidney-targeting fluorophores NHcy with tunable emissions from NIR-I to NIR-II. Among these, NHcy-8 is the first small-molecule NIR-II dye without a renal clearance moiety, designed specifically for kidney-targeting imaging. Building on this class of NIR-II fluorophore, the first NIR-II small-molecule kidney-targeting pH probe NIR-II-pH is developed, which exhibits a desirable kidney distribution after intravenous injection and is fluorescent only after activation by acidosis. NIR-II in vivo fluorescence/photoacoustic imaging of kidney disease models induced by cisplatin and renal I/R injury using NIR-II-pH reveals increasingly severe metabolic acidosis as the disease progressed, enabling sensitive detection of the onset of acidosis 36 h (cisplatin group) earlier than clinical methods. Thus, this study introduces a practical NIR-II kidney-targeting probe and provides a useful molecular blueprint for guiding kidney-targeting NIR-II fluorophores as diagnostic aids for kidney diseases., (© 2024 Wiley‐VCH GmbH.)

The thyroid hormone (TH) system is susceptible to the toxic effects of polychlorinated biphenyls (PCBs). Pollutants may disrupt the TH system by binding to serum TH transport proteins or interacting with thyroid hormone receptors (TRs) in target cells. However, the molecular mechanism of interaction with the Thyroid Hormone Receptor Beta (TRβ) is not fully understood. This study employed fluorescence, UV-visible absorption, three-dimensional fluorescence, and Fourier-transform infrared spectroscopy, along with molecular docking and molecular dynamics simulations, to investigate the interaction between TRβ and PCBs. Moreover, molecular docking and fluorescence resonance energy transfer (FRET) findings suggest that TRβ and PCBs underwent resonance energy transfer consistent with Förster's theory. The root mean square deviation (RMSD) and docking outcomes indicate that the TRβ-PCB29 complex exhibited optimal structural stability. Thus, the study concludes that integrating spectroscopic data with molecular docking is essential for a comprehensive analysis. Further analysis of intermolecular interactions using quantum chemistry and reduced density gradient analysis (RDG) analysis revealed that van der Waals forces are the primary drivers of PCBs to TRβ., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The accumulation of chromium (Cr) and copper (Cu) in soil during industrialization and modernization poses an extreme threat to crops. Poly-γ-glutamic acid (γ-PGA) has the potential to stabilize heavy metals in soil through chelation because of the numerous carboxyl groups in its side chain. The rhizosphere microbiome contributes to plant detoxification by participating in heavy metal passivation. However, it is still unclear whether γ-PGA can alleviate the toxicity of Cr and Cu to plants and whether this effect is associated with changes in the rhizosphere microbiome assembly. Here, we found that γ-PGA application significantly reduced the content of Cr or Cu in cucumber plants by 67.45%-86.77% and 94.67%-98.21, respectively, and alleviated the oxidative stress of Cr or Cu to plants. Moreover, γ-PGA significantly increased the biomass of cucumber fruits in the plot experiment by 13.5% and 25.3% under Cr and Cu stress, respectively. The content of Cr or Cu in the cucumber fruit was below limits of detection, in contrast to the 31.23 mg/kg Cr or 9.86 mg/kg Cu detected in the no-γ-PGA treatment. γ-PGA effectively chelated Cr and Cu in vitro, and less than 30% of their chelates were degraded in 20 weeks, suggesting the strong stability of these chelates. γ-PGA significantly altered the rhizosphere bacterial community composition of cucumber by enriching phyla Gemmatimonadota, Acidobacteriota and Firmicutes, and genera Gemmatimonas and Stenotrophomonas, which potentially involved in reducing the mobility of Cr and Cu in soils. Furthermore, γ-PGA significantly enriched taxa assigned to plant growth-promoting bacteria (PGPB). Together, our results suggest that γ-PGA can reduce the Cr and Cu contents in cucumber, and this process is strongly associated with the chelation capacity of γ-PGA and its effects on rhizosphere microbiome composition. These results highlight the exciting potential to use γ-PGA for the remediation of heavy metal-contaminated soils., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Itaconate is a key anti-inflammatory/antibacterial metabolite in pathogen-macrophage interactions that induces adaptive changes in Pseudomonas aeruginosa-exposed airways. However, the impact and mechanisms underlying itaconate metabolism remain unclear. Our study reveals that itaconate significantly upregulates the expression of pyoverdine in P. aeruginosa and enhances its tolerance to tobramycin. Notably, the enzymes responsible for efficient itaconate metabolism, PaIch and PaCcl, play crucial roles in both utilizing itaconate and clearing its toxic metabolic intermediates. By using protein crystallography and molecular dynamics simulations analyses, we have elucidated the unique catalytic center and substrate-binding pocket of PaIch, which contribute to its highly efficient catalysis. Meanwhile, analysis of PaCcl has revealed how interactions between domains regulate the conformational changes of the active sites and binding pockets, influencing the catalytic process. Overall, our research uncovers the significance and mechanisms of PaIch and PaCcl in the efficient metabolism of itaconate by P. aeruginosa., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Hyperproliferative keratinocytes and subcutaneous inflammation contribute to the characteristic symptoms of psoriasis, including erythema, scales, or scaly plaques on the skin. These symptoms significantly affect patients' quality of life and cause severe physical and psychological distress. However, current treatment strategies have limited therapeutic effect and may lead to adverse side effects. In this study, we present the novel organic photosensitizer TBTDC [5-(((5-(7-(4-(diphenylamino)phenyl)benzo[c][1,2,5]thiadiazol-4-yl)thiophen-2-yl)methylene)amino)-3-methylthiophene-2,4-dicarbonitrile] nanoparticles (NPs) with aggregation-induced emission (AIE) characteristics to mediate photodynamic therapy (TBTDC NP-PDT) for psoriasis treatment. We demonstrate that TBTDC NPs effectively generate reactive oxygen species upon light irradiation and lead to significant apoptosis of psoriatic keratinocytes. Furthermore, TBTDC NPs exhibit high cellular uptake in diseased keratinocytes and induce endoplasmic reticulum stress (ERS)-mediated autophagy, which can also enhance apoptosis. Importantly, TBTDC NPs show no cytotoxicity toward keratinocytes. These unique properties of TBTDC NPs enable remarkable therapeutic effects against psoriasis-like skin lesions and related inflammation in vivo. Overall, our AIE-active TBTDC NP-PDT represents a promising strategy for treating psoriasis in clinical settings., Competing Interests: Author contributions: P.Z.: Conceptualization, methodology, data curation, visualization, investigation, and writing—original draft. Z.W.: Synthesis, methodology, characterization, investigation, and validation. Z.Y.: Methodology, investigation, and formal analysis. T.T.: Methodology, investigation, and formal analysis. Y.L.: Methodology and formal analysis. W.Z.: Methodology. Y.H.: Investigation. T.C.: Methodology. J.L.: Investigation. C.N.: Investigation. Z.W.: Investigation. G.H.: Conceptualization, funding acquisition, and writing—review and editing. Y.L.: Conceptualization, resources, and writing—review and editing. Y.C.: Conceptualization, funding acquisition, supervision, and writing—review and editing. Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Ping Zhu et al.)

Fusarium wilt, caused by Fusarium oxysporum f. sp. cubense Tropical Race 4 ( Foc TR4), poses a significant threat to banana production globally, thereby necessitating effective biocontrol methods to manage this devastating disease. This study investigates the potential of Bacillus siamensis strain JSZ06, isolated from smooth vetch, as a biocontrol agent against Foc TR4. To this end, we conducted a series of in vitro and in vivo experiments to evaluate the antifungal activity of strain JSZ06 and its crude extracts. Additionally, genomic analyses were performed to identify antibiotic synthesis genes, while metabolomic profiling was conducted to characterize bioactive compounds. The results demonstrated that strain JSZ06 exhibited strong inhibitory activity against Foc TR4, significantly reducing mycelial growth and spore germination. Moreover, scanning and transmission electron microscopy revealed substantial ultrastructural damage to Foc TR4 mycelia treated with JSZ06 extracts. Genomic analysis identified several antibiotic synthesis genes, and metabolomic profiling revealed numerous antifungal metabolites. Furthermore, in pot trials, the application of JSZ06 fermentation broth significantly enhanced banana plant growth and reduced disease severity, achieving biocontrol efficiencies of 76.71% and 79.25% for leaves and pseudostems, respectively. In conclusion, Bacillus siamensis JSZ06 is a promising biocontrol agent against Fusarium wilt in bananas, with its dual action of direct antifungal activity and plant growth promotion underscoring its potential for integrated disease management strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ruan, Nong, Jintrawet, Fan, Fu, Zheng, Li and Wang.)

Microbiomes are the most important members involved in the regulation of soil nitrogen metabolism. Beneficial interactions between plants and microbiomes contribute to improving the nitrogen utilization efficiency. In this study, we investigated the Apiaceae medicinal plant Angelica dahurica var. formosana . We found that under a low-nitrogen treatment, the abundance of carbon metabolites in the rhizosphere secretions of A. dahurica var. formosana significantly increased, thereby promoting the ratio of C to N in rhizosphere and nonrhizosphere soils, increasing carbon sequestration, and shaping the microbial community composition, thus promoting a higher yield and furanocoumarin synthesis. Confirmation through the construction of a synthetic microbial community and feedback experiments indicated that beneficial plant growth-promoting rhizobacteria play a crucial role in improving nitrogen utilization efficiency and selectively regulating the synthesis of target furanocoumarins under low nitrogen conditions. These findings may contribute additional theoretical evidence for understanding the mechanisms of interaction between medicinal plants and rhizosphere microorganisms.

To explore a noninvasive method for diagnosis of SEA-thalassemia and to investigate whether the regional factors affect the accuracy of this method. The method involved using a public database and bioinformatics software to construct parental haplotypes for proband and predicting fetal genotypes using relative haplotype dosage. We screened and downloaded sequencing data of couples who were both SEA-thalassemia carriers from the China National Genebank public data platform, and matched the sequencing data format with that of the reference panel using Ubuntu system tools. We then used Beagle software to construct parental haplotypes, predicted fetal haplotypes by relative haplotype dosage. Finally, we used Hidden Markov Model and Viterbi algorithm to determine fetal pathogenic haplotypes. All noninvasive fetal genotype diagnosis results were compared with gold standard gap-PCR electrophoresis results. Our method was successful in diagnosing 13 families with SEA-thalassemia carriers. The best diagnostic results were obtained when Southern Chinese Han was used as the reference panel, and 10 families showed full agreement between our noninvasive diagnostic results and the gap-PCR electrophoresis results. The accuracy of our method was higher when using a Chinese Han as the reference panel for haplotype construction in the Southern Chinese Han region as opposed to Beijing Chinese region. The combined use of public databases and relative haplotype dosage for diagnosing SEA-thalassemia is a feasible approach. Our method produces the best noninvasive diagnostic results when the test samples and population reference panel are closely matched in both ethnicity and geography. When constructing parental haplotypes with our method, it is important to consider the effect of region in addition to population background alone.

Cherax quadricarinatus exhibit sexual dimorphism, with males outpacing females in size specification and growth rate. However, there is limited understanding of the molecular mechanisms underlying sex determination and sex differentiation in crustaceans. To study the differences between intersex individuals and normal individuals, this study counted the proportion of intersex individuals in the natural population, collected the proportion of 7 different phenotypes in 200 intersex individuals, and observed the differences in tissue sections. RNA-seq was used to study the different changes in the transcriptome of normal and intersex gonads. The results showed that: the percentage of intersex in the natural population was 1.5 %, and the percentage of different types of intersex ranged from 0.5 % to 22.5 %; the sections revealed that the development of normal ovaries was stagnant at the primary oocyte stage when intersex individuals with ovaries were present; We screened for pathways and genes that may be associated with gonadal development and sex, including ovarian steroid synthesis, estrogen signaling pathway, oocyte meiosis, progesterone-mediated oocyte maturation, etc. Relevant genes including tra2a, dmrta2, ccnb2, foxl2, and smad4. This study provides an important molecular basis for sex determination, sex-controlled breeding, and unisex breeding in red crayfish., Competing Interests: Declaration of competing interest All authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Triptolide (TP) is the major bioactive component of traditional Chinese medicine Tripterygium wilfordii Hook. F., a traditional Chinese medicinal plant categorized within the Tripterygium genus of the Celastraceae family. It is recognized for its therapeutic potential in addressing a multitude of diseases. Nonetheless, TP is known to exhibit multi-organ toxicity, notably hepatotoxicity, which poses a significant concern for the well-being of patients undergoing treatment. The precise mechanisms responsible for TP-induced hepatotoxicity remain unresolved. In our previous investigation, it was determined that TP induces heightened hepatic responsiveness to exogenous lipopolysaccharide (LPS). Additionally, natural killer (NK) cells were identified as a crucial effector responsible for mediating hepatocellular damage in this context. However, associated activating receptors and the underlying mechanisms governing NK cell represented innate lymphoid cell (ILC) activation remained subjects of inquiry and were not yet investigated. Herein, activating receptor Killer cell lectin like receptor K1 (NKG2D) of group 1 ILCs was specifically upregulated in TP- and LPS-induced acute liver failure (ALF), and in vivo blockade of NKG2D significantly reduced group 1 ILC mediated cytotoxicity and mitigated TP- and LPS-induced ALF. NKG2D ligand UL16-binding protein-like transcript 1 (MULT-1) was found upregulated in liver resident macrophages (LRMs) after TP administration, and LRMs did exhibit NK cell activating effect. Furthermore, M1 polarization of LRMs cells was observed, along with an elevation in intracellular tumor necrosis factor (TNF)-α levels. In vivo neutralization of TNF-α significantly alleviated TP- and LPS-induced ALF. In conclusion, the collaborative role of group 1 ILCs and LRMs in mediating hepatotoxicity was confirmed in TP- and LPS-induced ALF. TP-induced MULT-1 expression in LRMs was the crucial mechanism in the activation of group 1 ILCs via MULT-1-NKG2D signal upon LPS stimulation, emphasizing the importance of infection control after TP administration., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Floral scent (FS) plays a crucial role in the ecological functions and industrial applications of plants. However, the physiological and metabolic mechanisms underlying FS formation remain inadequately explored. Our investigation focused on elucidating the differential formation mechanisms of 2-phenylethanol (2-PE) and benzyl alcohol (BA) by examining seven related enzyme concentrations and the content of soluble sugar, soluble proteins, carbon (C) and nitrogen (N), as well as the C/N ratio. The findings revealed that the peak content of 2-PE in M. 'Praire Rose' and BA in M. 'Lollipop' occurred during the end flowering stage (S4) and flowering stage (S3) periods, respectively. The enzyme concentration change trends of phenylpyruvate decarboxylase (PDL), phenylacetaldehyde reductase (PAR), soluble protein, C, N, and C/N ratio changes during the S3-S4 period in M. 'Praire Rose' and M. 'Lollipop' were entirely opposite. Correlation and PCA analysis demonstrated that the content of CYP79D73 (a P450) and N, and the C/N ratio were key factors in 2-PE production in M. 'Praire Rose'. The production of BA in M. 'Lollipop' was more influenced by the content of phenylacetaldehyde synthase (PAAS), CYP79D73, and soluble sugar. As CYP79D73 exits oppositely in correlation to 2-PE ( M. 'Praire Rose') and BA ( M. 'Lollipop'), it is hypothesized that CYP79D73 was postulated as the primary factor contributing to the observed differences of 2-PE ( M. 'Praire Rose') and BA ( M. 'Lollipop') formation. These results carry significant implications for crabapple aromatic flower breeding and the essential oil industry etc.

Pseudomonas aeruginosa is a highly pathogenic bacterium known for its ability to sense and coordinate the production of virulence factors in response to host immune responses. However, the regulatory mechanisms underlying this process have remained largely elusive. In this study, we investigate the two-component system CprRS in P. aeruginosa and unveil the crucial role of the sensor protein CprS in sensing the human host defense peptide LL-37, thereby modulating bacterial virulence. We demonstrate that CprS acts as a phosphatase in the presence of LL-37, leading to the phosphorylation and activation of the response regulator CprR. The results prove that CprR directly recognizes a specific sequence within the promoter region of the HigBA toxin-antitoxin system, resulting in enhanced expression of the toxin HigB. Importantly, LL-37-induced HigB expression promotes the production of type III secretion system effectors, leading to reduced expression of proinflammatory cytokines and increased cytotoxicity towards macrophages. Moreover, mutations in cprS or cprR significantly impair bacterial survival in both macrophage and insect infection models. This study uncovers the regulatory mechanism of the CprRS system, enabling P. aeruginosa to detect and respond to human innate immune responses while maintaining a balanced virulence gene expression profile. Additionally, this study provides new evidence and insights into the complex regulatory system of T3SS in P. aeruginosa within the host environment, contributing to a better understanding of host-microbe communication and the development of novel strategies to combat bacterial infections., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Song et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study aimed to introduce an immunosensor for measuring amyloid β 42 (Aβ 42 ) levels by aggregation-induced enhanced electrochemiluminescence (ECL). Metal-organic gels (MOGs) are novel soft materials with advantages such as high gel stability, good light-emitting properties, and easy preparation. This study used silver nanoparticle metal-organic gel (Ag-MOG) as a substrate to connect Aβ 42 -Ab2 and the cathodoluminescent probe. Potassium persulfate was used as a co-reactant that could emit a high ECL signal. CuS@Au had the benefits of a relatively large surface area with excellent carrier function; therefore, it was used as a substrate to load a large amount of Aβ 42 -Ab1, significantly improving the immunosensor sensitivity. The ECL intensity of Aβ 42 was linear in the range of 0.01 pg/mL to 250 ng/mL with a detection limit of 2.2 fg/mL (S/N = 3) under optimized detection conditions. This ECL immunosensor has been successfully applied to detect Aβ 42 in human serum with the advantages of excellent stability and high selectivity. This method not only expands the potential applications of ECL immunosensors based on biological testing and clinical diagnosis but also provides a viable approach to basic clinical testing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Thalassemia is a genetic disease that seriously affects the health of the fetus. At present, invasive prenatal diagnosis is the main method of thalassemia screening, but invasive prenatal diagnosis has the risk of fetal abortion. The discovery of cell-free fetal DNA (cffDNA) in the peripheral blood of pregnant women provides the possibility for non-invasive prenatal diagnosis (NIPD). Rapid and efficient capture of mutational information on cffDNA in maternal plasma can help prevent the birth of children with thalassemia major. Currently, strategies for cffDNA-based NIPD of thalassemia include the detection of paternal mutations in maternal plasma, detection of a proportion of wild and mutant alleles in maternal plasma, linkage disequilibrium single nucleotide polymorphism (SNP) based on pedigree probands, and prediction of fetal genotypes by bioinformatics combined with population information. Therefore, this paper will focus on the above aspects, in order to provide an essential reference to the prevention and treatment of thalassemia.

Pseudomonas aeruginosa, a versatile bacterium, has dual significance because of its beneficial roles in environmental soil processes and its detrimental effects as a nosocomial pathogen that causes clinical infections. Understanding adaptability to environmental stress is essential. This investigation delves into the complex interplay of two-component system (TCS), specifically ParRS and CprRS, as P. aeruginosa interprets host signals and navigates stress challenges. In this study, through phenotypic and proteomic analyses, the nuanced contributions of ParRS and CprRS to the pathogenesis and resilience mechanisms were elucidated. Furthermore, the indispensable roles of the ParS and CprS extracellular sensor domains in orchestrating signal perception remain unknown. Structural revelations imply a remarkable convergence of TCS sensors in interacting with host peptides, suggesting evolutionary strategies for bacterial adaptation. This pioneering work not only established links between cationic antimicrobial peptide (CAMP) resistance-associated TCSs and virulence modulation in nosocomial bacteria, but also transcended conventional boundaries. These implications extend beyond clinical resistance, permeating into the realm of soil revitalization and environmental guardianship. As it unveils P. aeruginosa intricacies, this study assumes a mantle of guiding strategies to mitigate clinical hazards, harness environmental advantages, and propel sustainable solutions forward., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Triptolide (TP) exhibits therapeutic potential against multiple diseases. However, its application in clinics is limited by TP-induced hepatoxicity. TP can activate invariant natural killer T (iNKT) cells in the liver, shifting Th1 cytokine bias to Th2 cytokine bias. The damaging role of iNKT cells in TP-induced hepatoxicity has been established, and iNKT cell deficiency can mitigate hepatotoxicity. However, the activation of iNKT cells in vitro by TP requires the presence of antigen-presenting cells. Therefore, we hypothesized that TP could induce dendritic cells (DCs) to activate iNKT cells, thereby leading to hepatotoxicity. The hepatic conventional DCs (cDCs) exhibited immunogenic activities after TP administration, upregulating the expression of CD1d, co-stimulatory molecules, and IL-12. Neutralization with IL-12p40 antibody extenuated TP-induced hepatotoxicity and reduced iNKT cell activation, suggesting that IL-12 could cause liver injury by activating iNKT cells. TP triggered the activation and upregulation of STING signaling pathway and increased endoplasmic reticulum (ER) stress. Downregulation of STING reduced cDC immunogenicity, inhibiting the activation of iNKT cells and hepatic damage. These indicated the regulatory effects of STING pathway on cDCs and iNKT cells, and the important roles it plays in hepatoxicity. ER stress inhibitor, 4-phenylbutyrate (4-PBA), also suppressed iNKT cell activation and liver injury, which might be regulated by the STING signaling pathway. Our results demonstrated the possible mechanisms underlying TP-induced hepatoxicity, where the activation of cDCs and iNKT cells was stimulated by upregulated STING signaling and increased ER stress as a result of TP administration., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Cadmium (Cd), a common heavy metal in the environment, is associated with cognitive impairment. In the present study, we carried out a preliminary inquiry to explore whether Cd causes neurotoxicity by regulating the JAK2/STAT3 signaling pathway and affecting the expression of klotho genes in vivo and in vitro, providing clues for the mechanism of Cd-induced cognitive dysfunction. The rat samples were injected with Cd chloride solution for 14 weeks, and the memory function of the rats was detected. Different concentrations of Cd and JAK2/STAT3 signaling pathway inhibitors were used to treat PC12 cells and thus detect the apoptosis rate. The protein expression levels of JAK2, p-JAK2, STAT3, p-STAT3, and klotho in rat and PC12 cell were detected by ELISA and Western blot, respectively. With the increase in exposure dose, the memory function of rats was severely impaired. The expression of p-JAK2 and p-STAT3 proteins was significantly up-regulated, whereas that of klotho was significantly down-regulated both in vivo and in vitro (p < 0.05). In comparison with the high-dose Cd exposure group, after adding tyrphostin AG490 (AG490), the apoptosis rate of PC12 cells increased, whereas the phosphorylation levels of JAK2 and STAT3 in the cells decreased significantly (p < 0.05). Cd exposure may cause neurotoxicity by regulating the JAK2/STAT3 signaling pathway and down-regulating klotho protein expression, leading to cognitive dysfunction., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In this work, a label-free electrochemical immunosensor using tin sulfide/nickel cobalt metal-organic frameworks (SnS 2 /NiCo MOFs) was established for the sensitive detection of cortisol. First, SnS 2 /NiCo MOFs were synthesized by doping SnS 2 with NiCo MOF nanocubes by a hydrothermal method. Then, gold nanoparticles (AuNPs) were grown in situ on SnS 2 /NiCo MOFs for electrochemical detection. The use of SnS 2 /NiCo MOFs promoted the electron transfer rate of AuNPs and enhanced the electrochemical sensing performance of AuNPs@SnS 2 /NiCo MOFs-modified electrodes. The large specific surface area of AuNPs@SnS 2 /NiCo MOFs provides more active sites for antibody loading. After the prepared immunosensor was incubated with the target analyte, cortisol, the electron transfer impedance increased and the amperometric response decreased, thus establishing a highly sensitive immunosensing method. The sensor had a linear range of 100 fg/mL to 100 ng/mL and a low detection limit of 29 fg/mL. The sensor showed good accuracy and practicability and could be used for the determination of cortisol in saliva., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: It is well documented that angiotensin II (Ang II) elevation promotes apoptosis of podocytes in vivo and vitro , but the potential mechanism is still oscular. The current study is aimed at probing into the assignment of cysteine-rich protein 61 (Cyr61) in Ang II-induced podocyte apoptosis., Methods: Podocytes were treated with Ang II (10 -6  mol/L) for 48 hours to establish an injury model in vitro. Western blot assays were detected the expression of Cyr61, Cyt-c, Bax, and Bcl-2. Gene microarray was used to analyze the expression of mRNAs after treatment with Ang II. CRISPR/Cas9 technology was used to knock down Cyr61 and overexpress TXNIP gene, respectively., Results: The expression of Cyr61, TXNIP, Cyt-c, and Bax in podocytes treated with Ang II were upregulated, but the expression and apoptotic rates of Bcl-2 in podocytes were inhibited. The level of the above factors was not significantly different after the knockdown of Cyr61 with Ang II in podocytes. In Ang II group, when knocked down Cyr61, the expressed level of TXNIP, Cyt-c, and Bax was diminished after Ang II treatment; interestingly Bcl-2 expression and podocyte apoptotic rate were reduced. Under the stimulation of Ang II, the expression of Cyt-c and Bax were growing, whereas Bcl-2 was reduced, and the apoptotic rates were higher in the TXNIP overexpression group. Cyt-c and Bax were put on, whereas that of Bcl-2 was to be cut down when the Cyr61 was knockdown, and the apoptotic rates were gained in the TXNIP overexpression+Cyr61 knockdown group., Conclusions: The results of the study extrapolate that Cyr61 plays a dominant role in Ang II-induced podocyte apoptosis. Additionally, Cyr61 may mediate the Ang II-induced podocyte apoptosis by promoting the expression of TNXIP., Competing Interests: No potential conflict of interest was reported by the authors., (Copyright © 2023 Jingxue Ma et al.)

The fast-developing synthetic biology (SB) has provided many genetic tools to reprogram and engineer cells for improved performance, novel functions, and diverse applications. Such cell engineering resources can play a critical role in the research and development of novel therapeutics. However, there are certain limitations and challenges in applying genetically engineered cells in clinical practice. This literature review updates the recent advances in biomedical applications, including diagnosis, treatment, and drug development, of SB-inspired cell engineering. It describes technologies and relevant examples in a clinical and experimental setup that may significantly impact the biomedicine field. At last, this review concludes the results with future directions to optimize the performances of synthetic gene circuits to regulate the therapeutic activities of cell-based tools in specific diseases., (© 2023. The Author(s).)

Background: Super-enhancer (SE) refers to a regulatory element with super transcriptional activity, which can enrich transcription factors and drive gene expression. SE-related genes play an important role in the pathogenesis of malignant tumors, including hepatocellular carcinoma (HCC)., Methods: The SE-related genes were obtained from the human super-enhancer database (SEdb). Data from the transcriptome analysis and related clinical information with HCC were obtained from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) database. The upregulated SE-related genes from TCGA-LIHC were identified by the DESeq2R package. Multivariate Cox regression analysis was used to construct a four-gene prognostic signature. According to the median risk score, HCC patients were divided into high-risk and low-risk group patients., Results: The Kaplan-Meier (KM) curve showed that a significantly worse prognosis was found for the high-risk group ( P <0.001). In the TCGA-LIHC dataset, the area under the curve (AUC) values were 0.737, 0.662, and 0.667 for the model predicting overall survival (OS) over 1-, 3-, and 5- years, respectively, indicating the good prediction ability of our prediction model. This model's prognostic value was further validated in the LIRI-JP dataset and HCC samples (n=65). Furthermore, we found that higher infiltration level of M0 macrophages and upregulated of CTLA4 and PD1 in the high-risk group, implying that immunotherapy could be effective for those patients., Conclusion: These results provide further evidence that the unique SE-related gene model could accurately predict the prognosis of HCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wei, Zhou, Long, Lin, Qiu, Chen, Huang, Qiu, Jiang, Wen, Liu, Li, Nong, Guo, Yu and Zhou.)

Background: Tripterygium wilfordii Hook. F (TWHF) is used as a traditional Chinese medicine, called thunder god vine, based on its efficacy for treating inflammatory diseases. However, its hepatotoxicity has limited its clinical application. Triptolide (TP) is the major active and toxic component of TWHF. Previous studies reported that a toxic pretreatment dose of TP leads to hepatic intolerance to exogenous lipopolysaccharide (LPS) stimulation, and to acute liver failure, in mice, but the immune mechanisms of TP-sensitised hepatocytes and the TP-induced excessive immune response to LPS stimulation are unknown., Purpose: To identify both the key immune cell population and mechanism involved in TP-induced hepatic intolerance of exogenous LPS., Study Design: In vitro and in vivo experiments were conducted to investigate the inhibitory signal of natural killer (NK) cells maintained in hepatocytes, and the ability of TP to impair that signal., Methods: Flow cytometry was performed to determine NK cell activity and hepatocyte histocompatibility complex (MHC) class I molecules expression; the severity of liver injury was determined based on blood chemistry values, and drug- or cell-mediated hepatocellular damage, by measuring lactate dehydrogenase (LDH) release. In vivo H-2K b transduction was carried out using an adeno-associated viral vector., Results: Interferon (IFN)-γ-mediated necroptosis occurred in C57BL/6N mice treated with 500 μg TP/kg and 0.1 mg LPS/kg to induce fulminant hepatitis. Primary hepatocytes pretreated with TP were more prone to necroptosis when exposed to recombinant murine IFN-γ. In mice administered TP and LPS, the intracellular IFN-γ levels of NK cells increased significantly. Subsequent study confirmed that NK cells were activated and resulted in potent hepatocellular toxicity. In vivo and in vitro TP administration significantly inhibited MHC class I molecules in murine hepatocytes. An in vitro analysis demonstrated the susceptibility of TP-pretreated hepatocytes to NK-cell-mediated cytotoxicity, an effect that was significantly attenuated by the induction of hepatocyte MHC-I molecules by IFN-α. In vivo induction or overexpression of hepatocyte MHC-I also protected mouse liver against TP and LPS-induced injury., Conclusion: The TP-induced inhibition of hepatocyte MHC-I molecules expression leads to hepatic intolerance to exogenous LPS and NK-cell mediated cytotoxicity against self-hepatocytes. These findings shed light on the toxicity of traditional Chinese medicines administered for their immunomodulatory effects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Cholestasis is a common, chronic liver disease that may cause fibrosis and cirrhosis. Tripterygium wilfordii Hook.f (TWHF) is a species in the Euonymus family that is commonly used as a source of medicine and food in Eastern and Southern China. Triptolide (TP) is an epoxy diterpene lactone of TWHF, as well as the main active ingredient in TWHF. Here, we used a mouse model of common bile duct ligation (BDL) cholestasis, along with cultured human intrahepatic biliary epithelial cells, to explore whether TP can relieve cholestasis. Compared with the control treatment, TP at a dose of 70 or 140 μg/kg reduced the serum levels of the liver enzymes alanine transaminase, aspartate aminotransferase, and alkaline phosphatase in mice; hematoxylin and eosin staining also showed that TP reduced necrosis in tissues. Both in vitro and in vivo analyses revealed that TP inhibited cholangiocyte proliferation by reducing the expression of RelB. Immunohistochemical staining of CK19 and Ki67, as well as measurement of Ck19 mRNA levels in hepatic tissue, revealed that TP inhibited the BDL-induced ductular reaction. Masson 3 and Sirius Red staining for hepatic hydroxyproline showed that TP alleviated BDL-induced hepatic fibrosis. Additionally, TP substantially inhibited BDL-induced hepatic inflammation. In summary, TP inhibited the BDL-induced ductular reaction by reducing the expression of RelB in cholangiocytes, thereby alleviating liver injury, fibrosis, and inflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yuan, Wang, Zhang, Miao, Tang, Yuan, Nong, Duan, Zhang, Jiang and Yu.)

Ferroptosis, an iron-dependent form of selective cell death, is involved in the development of many cancers. However, the role of ferroptosis-related genes (FRGs) in kidney renal papillary cell carcinoma (KIRP) is unclear. In this study, we examined the mRNA expression profiles and clinical data of patients with KIRP from the TCGA cohort. Consequently, 41 differentially-expressed FRGs were screened using the limma package, and 17 prognostic-related FRGs were identified by survival analysis and univariate Cox regression analyses. Thereafter, a ferroptosis-related gene prognostic index (FRGPI) was constructed based on five FRGs ( AKR1C3 , SAT1 , FANCD2 , HSBP1 and SQLE ), using lasso Cox and multivariate Cox regression analyses. KIRP patients with high FRGPI scores displayed worse outcomes. Furthermore, the FRGPI was shown to be a reliable independent prognostic factor in both the training and testing cohorts. Comprehensive analysis also showed that the FRGPI can distinguish gene mutation, functional enrichment of immune cells and molecular function-related pathways. Interestingly, low FRGPI score could be more benefit from immune checkpoint inhibitors (ICIs) therapy. Then, the two hub prognostic genes ( AKR1C3 and FANCD2 ) as a risk gene for KIRP were identified based on the FRGPI module, and the expression profiles of these two genes were validated using human KIRP cells, besides, we furthermore discovered that Fancd2 is significantly up-regulated in most cancers and is associated with prognosis. In conclusion, these findings showed that FRGPI can accurately predict the prognosis of patients with KIRP, suggesting that this risk model is a promising prognostic biomarker for these patients. Moreover, targeting ferroptosis ( FANCD2 ) could be a potential therapeutic alternative for various cancers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yin, Lin, Liang, Wei, Huang, Qin, Nong, Zeng, Nong and Qin.)

Ethnopharmacological Relevance: Triptolide (TP) is a major active ingredient and toxic component of Tripterygium wilfordii Hook F (TWHF), which exhibits multiple activities and remarkable hepatotoxicity, the latter of which limits its clinical application due to the risk of liver injury. Previous research has revealed the hepatotoxicity of TP resulting in liver hypersensitivity upon lipopolysaccharide (LPS) stimulation. However, existing research has not elucidated the potential immune mechanism such as Th17/Treg imbalance in TP-induced hepatic excessive immune response to exogenous LPS., Aim of the Study: To investigate the role of Th17/Treg imbalance in TP-induced hepatic excessive immune response to exogenous LPS., Materials and Methods: Mice were administered with TP, LPS, neutralization antibody and small molecule inhibitor respectively. Serum transaminase level was measured to determine the severity of liver injury. Frequencies of liver Th17 and Treg cells were analyzed by flow cytometry. Serum cytokine levels were performed by ELSIA, and mRNA levels of liver cytokine were performed by qPCR. The status of neutrophil infiltration was performed by myeloperoxidase (MPO) IHC measurement. Morphological observation of liver was performed by hematoxylin and eosin (H&E) staining., Results: Mice given a single intragastric dose of TP (500 μg/kg) developed lethal fulminant hepatitis following intraperitoneal injection of LPS (0.1 mg/kg), characterized by low survival rate, severe liver injury, high levels of inflammation and neutrophil infiltration. Hepatic Th17/Treg imbalance emerged together with liver injury in these mice. Neutralization of IL-17A attenuated the liver injury and ameliorated the neutrophil infiltration. The TP-induced alteration of hepatic Th17/Treg balance was closely related to the outcome of immune-mediated acute liver injury triggered by LPS. Pretreatment with the STAT3 inhibitor AG490 effectively restored Th17/Treg balance, significantly reducing the production of IL-17A and finally attenuating the degree of liver injury., Conclusion: Hepatic Th17/Treg imbalance not only exacerbates TP- and LPS-induced liver injury, but also serves as an indispensable part in the mechanisms of TP-induced hepatic intolerance to exogenous endotoxin., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Weed control has received great attention due to its significant influence on crop yield and food production. Accurate mapping of crop and weed is a prerequisite for the development of an automatic weed management system. In this paper, we propose a weed and crop segmentation method, SemiWeedNet, to accurately identify the weed with varying size in complex environment, where semi-supervised learning is employed to reduce the requirement of a large amount of labelled data. SemiWeedNet takes the labelled and unlabelled images into account when generating a unified semi-supervised architecture based on semantic segmentation model. A multiscale enhancement module is created by integrating the encoded feature with the selective kernel attention, to highlight the significant features of the weed and crop while alleviating the influence of complex background. To address the problem caused by the similarity and overlapping between crop and weed, an online hard example mining (OHEM) is introduced to refine the labelled data training. This forces the model to focus more on pixels that are not easily distinguished, and thus effectively improve the image segmentation. To further exploit the meaningful information of unlabelled data, consistency regularisation is introduced by maintaining the context consistency during training, making the representations robust to the varying environment. Comparative experiments are conducted on a publicly available dataset. The results show the SemiWeedNet outperforms the state-of-the-art methods, and its components have promising potential in improving segmentation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nong, Fan and Wang.)

Background: Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD). Currently, microalbuminuria is mainly used as a diagnostic indicator of DN, but there are still limitations and lack of immune-related diagnostic markers. In this study, we aimed to explore diagnostic biomarkers associated with immune infiltration of DN., Methods: Immune-related differentially expressed genes (DEGs) were derived from those at the intersection of the ImmPort database and DEGs identified from 3 datasets, which were based on the Gene Expression Omnibus (GEO). Functional enrichment analyses were performed; a protein-protein interaction (PPI) network was constructed; and hub genes were identified by Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). After screening the key genes using least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE), a prediction model for DN was constructed. The predictive performance of the model was quantified by receiver-operating characteristic curve, decision curve analysis, and nomogram. Next, infiltration of 22 types of immune cells in DN kidney tissue was evaluated using cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT). Expression of diagnostic markers was analyzed in DN and control patient groups to determine the genes with the maximum diagnostic potential. Finally, we explored the correlation between diagnostic markers and immune cells., Results: Overall, 191 immune-related DEGs were identified, that primarily positively regulated with cell adhesion, T cell activation, leukocyte proliferation and migration, urogenital system development, lymphocyte differentiation and proliferation, and mononuclear cell proliferation. Gene sets were related to the PI3K-Akt, MAPK, Rap1, and WNT signaling pathways. Finally, CCL19 , CD1C , and IL33 were identified as diagnostic markers of DN and recognized in the 3 datasets [area under the curve (AUC) =0.921]. Immune cell infiltration analysis demonstrated that CCL19 was positively correlated with macrophages M1 (R=0.47, P<0.001) and macrophages M2 (R=0.75, P<0.001). CD1C was positively correlated with macrophages M1 (R=0.47, P<0.05), macrophages M2 (R=0.75, P<0.01), and monocytes (R=0.42, P<0.01). IL33 was positively correlated with macrophages M1 (R=0.45, P<0.05), macrophages M2 (R=0.74, P<0.01), and monocytes (R=0.41, P<0.01)., Conclusions: Our results provide evidence that CCL19 , CD1C , and IL33 , which are associated with immune infiltration, are the potential diagnostic biomarkers for DN candidates., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-1682/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Background: The impact of dietary guidelines on health in ethnic minority regions needs to be further explored because of multiple sociocultural factors. Therefore, this study was conducted to analyze the association between adherence to dietary guidelines and health risks in an elderly population in an ethnic minority region., Methods: A cross-sectional survey was conducted among 836 older adults in ethnic minority areas. They were asked to describe their daily dietary intake levels through a semi-quantitative food frequency questionnaire. The closeness coefficient for each study subject was calculated by using the technique for order preference by similarity to an ideal solution (TOPSIS), which measures the adherence to Dietary Guide for Elderly Adults (DGEA). Regression models were used to analyze the association between adherence and health risks., Results: The daily food of the elderly in this area comprised cereals and vegetables. They had low intake of milk, dairy products, and water and high intake of salt. The closeness coefficient for the total population was 0.51, and the adherence of this population to dietary guidelines for the elderly was low. In both the crude model and the models adjusted for covariates, the closeness coefficient was not significantly associated with clinical indicators and health outcomes (p > 0.05)., Conclusions: No association was found between adherence to large sample-based dietary guidelines and clinical indicators or health outcomes in ethnic minority populations. The applicability of dietary guidelines to ethnic minority areas and whether they yield the expected health benefits require further study., (© 2022. The Author(s).)

The abundance of gut microbiota is significantly decreased in patients with colorectal tumors compared to healthy groups. However, few studies have been conducted to correlate the differences in gut microbiota in colon cancer patients with different prognosis. In this study, we analysed the gut microbiota among patients with colon cancer and determined the microbial characteristics of COAD and divided the overall survival of COAD data into the high- and low-risk groups. In addition, we established a microbiome-related gene map and determined the association between microbial features and immune cell infiltration in COAD. In comparison with the low-risk group, the high risk group of COAD samples exhibited a decreased proportion of activated CD4 T cells as well as an increased proportion of M2 macrophages. The current data suggested that different gut flora backgrounds lead to different gene expression profiles, which in turn affect immune cell typing and colorectal tumor prognosis., Competing Interests: The authors declare that this research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflicts of interest., (Copyright © 2022 Jieyang Yu et al.)

Scrub typhus is often misdiagnosed in febrile patients, leading to antibiotic abuse and multiple complications. We conducted a retrospective record review at the Fourth Affiliated Hospital of Guangxi Medical University in China. Data were collected on 52 patients with a confirmed diagnosis of scrub typhus and complete clinical data. In addition, data were collected on 52 patients with bloodstream infection, 25 patients with HIV infection, 112 patients with common community-acquired pneumonia (CCAP), and 36 patients with severe community-acquired pneumonia (SCAP) to serve as control groups. The peripheral blood CD4 and CD8 counts, CD4/CD8 ratio, C-reactive protein, procalcitonin, alanine aminotransferase, aspartate aminotransferase, creatinine, and β2 microglobulin levels; and the white blood cell count and neutrophil percentage were compared between the scrub typhus and the control groups. The value of these biomarkers in the diagnosis of scrub typhus was assessed using receiver-operating characteristic curve analysis. The scrub typhus group had a significantly lower CD4 count and CD4/CD8 ratio than the bloodstream infection, CCAP, and SCAP groups, and a significantly greater CD4 count and CD4/CD8 ratio than the HIV infection group. In contrast, the scrub typhus group had a significantly greater CD8 count than the bloodstream infection and CCAP and SCAP groups, and it had a lower level of CD8 than the HIV infection group. The areas under the curve of CD4/CD8 were more than 0.93 in the receiver-operating characteristic curve analysis. These findings suggest that the CD4/CD8 ratio is a useful ancillary test for diagnosing scrub typhus.

Heterosis of grain yield is closely associated with heading date in crops. Gene combinations of the major heading date genes Ghd7, Ghd8, and Hd1 play important roles in enhancing grain yield and adaptation to ecological regions in rice. However, the predominant three-gene combinations for a specific ecological region remain unclear in both three-line and two-line hybrids. In this study, we sequenced these three genes of 50 cytoplasmic male sterile/maintainer lines, 31 photo-thermo-sensitive genic male sterile lines, and 109 restorer lines. Sequence analysis showed that hybrids carrying strong functional alleles of Ghd7 and Hd1 and non-functional Ghd8 are predominant in three-line hybrids and are recommended for rice production in the subtropics around 30°N/S. Hybrids carrying strong functional Ghd7 and Ghd8 and non-functional Hd1 are predominant in two-line hybrids and are recommended for low latitude areas around 23.5°N/S rich in photothermal resources. Hybrids carrying strong functional Ghd7 and Ghd8 and functional Hd1 were not identified in commercial hybrids in the middle and lower reaches of the Yangtze River, but they have high yield potential in tropical regions because they have the strongest photoperiod sensitivity. Based on these findings, two genic sterile lines, Xiangling 628S and C815S, whose hybrids often head very late, were diagnosed with these three genes, and Hd1 was targeted to be knocked out in Xiangling 628S and replaced with hd1 in C815S. The hybrids developed from both modified sterile lines in turn had appropriate heading dates and significantly improved grain yield. This study provides new insights for breeding design to develop hybrids for various regions., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Objectives: The associations between oil tea and type 2 diabetes (T2D) have been little studied in the population. This study aimed to evaluate whether oil tea intake is related to the reduced risk of T2D in adults., Methods and Study Design: A rural-based cross-sectional study was conducted in Gongcheng Yao Autonomous County, Guangxi, southern China (2018-2019), with a total of 3178 population included in the final analysis. A multivariable logistic regression model was used to analyze the associations between the intake frequency, daily intake of oil tea and the risk of T2D. We further compared the association differences between the daily intake of oil tea and the risk of diabetes under different dietary patterns, which were generated from food frequency intake data using principal factor analysis., Results: The differences in the frequency and daily intake of oil tea in both groups (diabetes group and the non-diabetes group) were statistically significant (p<0.05). After adjusting for age, sex, smoking status, physical activity, body mass index (BMI), compared with non-oil tea drinkers, intake ≥3 times /d had an inverse association with T2D (OR=0.417; 95% CI: 0.205-0.848, p<0.05); while daily intake of more than 600 mL/d but less than 900 mL/d was significantly associated with reduced T2D risk (OR=0.492; 95% CI: 0.284-0.852, p=0.011). In the Chinese traditional dietary and the plant-based dietary model, compared with the non-oil tea drinkers, the fourth intake group had a lower risk of diabetes, with an OR (95%CI) value of 0.500 (0.291-0.854) and 0.505 (0.298-0.855), respectively, but no statistical significance (All p>0.05)., Conclusions: Our study suggests that oil tea was associated with a reduced risk of T2D aged 30 years or older.