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Mi Tang,1,2,* Liling Xiong,3,* Jianghui Cai,2,4,* Xuejia Gong,2 Li Fan,1 Xiaoyu Zhou,1 Shasha Xing,1 Xiao Yang3 1Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 2School of medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 3Obstetrics Department, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 4Department of Pharmacy, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shasha Xing; Xiao Yang, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China, Email xingshasha1230@126.com; wcchgcptg@163.comPurpose: Intrahepatic cholestasis of pregnancy (ICP) is a disorder that characterized by maternal pruritus, abnormal liver function, and an elevation in total bile acid concentrations during pregnancy. Immune factors have been recognized as playing a vital role in the mechanism of ICP. However, the underlying mechanisms regulating dysfunctional immune cells and immune genes remain to be fully elucidated.Patients and Methods: Single-cell RNA sequencing and bulk RNA sequencing data of the placenta were downloaded from the SRA database. The AUCell package, Monocle package and SCENIC package were utilized to explored immune cell activity, cell trajectory and transcription factor, respectively. GO, KEGG, and GSEA were employed to explore potential biological mechanisms. Cell-cell communications were further investigated using the CellChat package. RT-PCR, and Western blot were used to verify the gene expression in placenta.Results: In placenta cells, macrophages were found to be significantly increased in ICP. Additionally, macrophages exhibited the highest immune gene score and were divided into four subclusters (MF1-4). Our analysis revealed significant elevations in MF2, associated with LPS response and antigen presentation, and MF4, associated with TNF and cytokine production. MF3 displayed an anti-inflammatory phenotype. MF1, closely related to ribosomes and proteins, exhibited a sharp decrease. Although ICP maintained an anti-inflammatory state, macrophage trajectories showed a gradual progression toward inflammation. Subsequently, we confirmed that cytokine- and chemokine-related signaling pathways were emphasized in macrophages. Within the CXCL signaling pathway, the increased expression of CXCL1 in macrophages can interact with CXCR2 in neutrophils, potentially inducing macrophage infiltration, stimulating neutrophil chemotaxis, and leading to an inflammatory response and cellular damage.Conclusion: In conclusion, we firstly revealed the transcriptional signatures of macrophages in ICP and discovered a tendency toward an inflammatory state. This study also provides new evidence that the CXCL1-CXCR2 axis may play an important role in the pathogenesis of ICP.Keywords: intrahepatic cholestasis of pregnancy, scRNA-Seq, bulk RNA-Seq, immune gene, macrophage

Jianzhong Hu,1 Martin Chandler,1 Christopher Matthew Manuel,1 Jorge Caicedo,2 Michael Denne,2 Bruce Ewenstein,2 Ali G Mokdad,2 Shan Xing,3 Michael Recht1,4,5 1American Thrombosis and Hemostasis Network, Rochester, NY, USA; 2Rare Diseases and Hematology, Takeda Pharmaceuticals, U.S.A., Inc, Lexington, MA, USA; 3US Value and Evidence Generation, Takeda Pharmaceuticals, U.S.A., Inc, Lexington, MA, USA; 4Yale Center for Bleeding and Clotting Disorders, Yale University School of Medicine, New Haven, CT, USA; 5National Bleeding Disorders Foundation, New York, NY, USACorrespondence: Michael Recht, National Bleeding Disorders Foundation, 7 Penn Plaza, New York, NY, 10001, USA, Tel +1 800-360-2846, Email mrecht@hemophilia.orgIntroduction: Intracranial hemorrhage (ICH), a serious complication in persons with hemophilia A (PWHA), causes high rates of mortality and morbidity. Identified ICH risk factors from patient data spanning 1998– 2008 require reassessment in light of changes in the current treatment landscape.Aim and methods: PWHA identified in the ATHNdataset were evaluated retrospectively to assess incidence of ICH and determine the association between ICH risk and key characteristics using time-to-event analyses (Cox proportional-hazards models, survival curves, and sensitivity analyses).Results: Over a median follow-up time of 10.7 patient-years, 135 of 7837 PWHA over 2 years of age in the ATHNdataset (1.7%) experienced an ICH. Stratification by prophylaxis status and inhibitor status resulted in an incidence rate (IR) ratio (IRR) (IR+/IR−) of 0.63 (95% confidence interval [CI], 0.43– 0.94; P=0.020) and 1.76 (95% CI, 0.97– 3.20; P=0.059), respectively. Characteristics associated with greater risk of developing ICH include being aged 2– 12 years; being covered by Medicaid; having had HIV, hepatitis C, or hypertension; and never having received factor VIII or prophylactic treatment. In multivariable analysis with interaction, the estimated hazard ratio for PWHA never receiving prophylaxis was 7.67 (95% CI, 2.24– 26.30), which shrunk to 2.03 (95% CI, 1.30– 9.12) in bootstrapping analysis and 3.09 in the highest-penalty ridge-regression analysis but was still significant. Inhibitor status was found not to be statistically associated with ICH in all analyses.Conclusion: These results align with previous studies demonstrating that prophylaxis confers a protective effect against ICH. Previously, inhibitor positivity had been shown to increase risk for ICH; however, this study did not corroborate those findings.Keywords: bleeding, factor VIII, health insurance, hematologic disease, prophylaxis, risk factors

Siwei Xing,1,* Xiaohao Ruan,1,* Jingyi Huang,1,* Jiaqi Yan,1 Wenhao Lin,1 Jinlun Huang,1 Jiacheng Liu,1 Da Huang,1 Rong Na,2 Danfeng Xu1 1Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Division of Urology, Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rong Na, Division of Urology, Department of Surgery, Queen Mary Hospital, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, People’s Republic of China, Email narong.hs@gmail.com Da Huang, Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, People’s Republic of China, Email huangdasjtu@gmail.comPurpose: To explore the impact of family history (FH) on renal cell carcinoma (RCC) and its pathological subtype clear cell RCC (ccRCC) in a Chinese population; a significant association has previously been determined not only in familial cancer syndrome but also in sporadic cases in western populations.Methods: Consecutive patients with kidney tumors from October 2017 to May 2021 at a tertiary hospital in Shanghai were enrolled in the study. Demographic and clinical information was collected, including age, gender, FH (positive or negative, types of cancers, degree of relatives, etc.), pathological diagnosis, and Fuhrman grades.Results: A positive FH of any cancer was observed in 26.5% of the RCC patients, while only 16.8% patients with benign kidney tumor were found to have a positive FH. A strong correlation was observed between FH of any cancers in first-degree relatives and RCC (odds ratio [OR]=4.60, 95% confidence interval [CI]: 1.95– 10.85, P=5.50× 10− 5) or ccRCC (OR=4.63, 95% CI: 1.95– 11.02, P=9.63× 10− 5). In subgroup analysis, FH of digestive cancers was significantly associated with RCC (OR=4.42, 95% CI: 1.35– 14.51, P=0.005) or ccRCC (OR=4.14, 95% CI: 1.25– 13.75, P=6.84× 10− 4). Similar results were found in multivariate analyses. However, no significant association was observed between FH and age at onset.Conclusion: FH was an independent risk factor for RCC and ccRCC in this Chinese population. FH of any cancer in first-degree relatives and FH of digestive cancers were found to be the most significant risk factors for kidney cancers.Keywords: Chinese population, family history, renal cell carcinoma, risk factor, multivariate regression analysis

Suke Xing,1,2 Hui Zhang,2 Ye Qiu,3 Mianluan Pan,1 Wen Zeng,2 Jianquan Zhang1 1Department of Respiratory and Critical Medicine, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, 518000, People’s Republic of China; 2Department of Respiratory Medicine, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 3Department of Comprehensive Internal Medicine, the Affiliated Tumour Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of ChinaCorrespondence: Jianquan Zhang, Department of Respiratory and Critical Medicine, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518000, Guangdong, People’s Republic of China, Tel +8613978123845, Fax +86755-23482484, Email jqzhang2002@126.comPurpose: To summarize the clinical characteristics, treatment and outcomes of transplant recipients infected with Talaromyces marneffei (TM).Materials and Methods: A retrospective analysis was performed on 2 patients with Talaromycosis marneffei (TSM) and transplants at the First Affiliated Hospital of Guangxi Medical University, and a systematic literature review was conducted simultaneously.Results: This article reported two patients after kidney transplantation who developed fever, cough within 3– 4 months. Their haemoglobin was decreased. Their chest computed tomography (CT) showed nodules. TM was detected in their blood or bronchoalveolar lavage fluid samples by next-generation sequencing (NGS). After antifungal treatment with voriconazole (VOR), one patient worsened, the other patient died. A total of 21 patients with TSM after transplants were reported in the literature review. Fourteen underwent kidney transplantation, 4 underwent liver transplantation, 2 underwent lung transplantation, and 1 underwent bone marrow transplantation. The median time from initiating the postoperative immunosuppressive therapy to the onset of symptoms or disease changes was 18 (0.5– 140) months. Among them, 9 patients developed fever, 7 patients developed cough or expectoration and 4 patients developed dyspnoea. Haemoglobin was decreased in 10 patients. Pulmonary nodules were found in 7 patients. Among the 21 patients, 7 were diagnosed by positive culture, 6 by biopsy, 5 by culture and biopsy. Of the 21 patients, 13 patients improved by antifungal therapy, 8 patients worsened or died. Seven patients who received amphotericin B followed by itraconazole (ITR) therapy all improved. Regarding the use of immunosuppressants in 12 patients, 9 patients had to discontinue or reduce their medications (6 patients improved, 3 patients worsened or died).Conclusion: Patients with TSM after transplant often have disseminated infections, involving the respiratory, hematopoietic and so on. Fever, cough, decreased haemoglobin and pulmonary nodules often occur approximately 18 months after surgery. The combined applications of culture, biopsy, NGS are helpful for an early diagnosis. Antifungal therapy with amphotericin B followed by itraconazole is recommended, and the dosage of the immunosuppressant should be adjusted timely.Keywords: Talaromyces marneffei, Talaromycosis marneffei, transplant recipients, immunosuppressants, antifungal drug

Yuliang Wang,1– 3 Linna Peng,1– 3 Hongyan Lu,1– 3 Zhanhao Zhang,1– 3 Shishi Xing,1– 3 Dandan Li,1– 3 Chunjuan He,1– 3 Tianbo Jin,1– 3 Li Wang1– 3 1Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, 712082, Shaanxi, People’s Republic of China; 2Engineering Research Center of Tibetan Medicine Detection Technology, Ministry of Education, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, 712082, People’s Republic of China; 3Key Laboratory of High Altitude Hypoxia Environment and Life Health, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, 712082, People’s Republic of ChinaCorrespondence: Li Wang Tel +86-15706028826Email wangli_xzmd@163.comBackground: We aimed to enrich the pharmacogenomic information of a Blang population (BP) from Yunnan Province in China.Methods: We genotyped 55 very important pharmacogene (VIP) variants from the PharmGKB database and compared their genotype distribution (GD) in a BP with that of 26 populations by the χ2 test. The minor allele frequency (MAF) distribution of seven significantly different single-nucleotide polymorphisms (SNPs) was conducted to compare the difference between the BP and 26 other populations.Results: Compared with the GD of 55 loci in the BP, among 26 studied populations, GWD, YRI, GIH, ESN, MSL, TSI, PJL, ACB, FIN and IBS were the top-10 populations, which showed a significantly different GD > 35 loci. CHB, JPT, CDX, CHS, and KHV populations had a significantly different GD < 20 loci. A GD difference of 27– 34 loci was found between the BP and 11 populations (LWK, CEU, ITU, STU, PUR, CLM, GBR, ASW, BEB, MXL and PEL). The GD of five loci (rs750155 (SULT1A1), rs4291 (ACE), rs1051298 (SLC19A1), rs1131596 (SLC19A1) and rs1051296 (SLC19A1)) were the most significantly different in the BP as compared with that of the other 26 populations. The genotype frequency of rs1800764 (ACE) and rs1065852 (CYP2D6) was different in all populations except for PEL and LWK, respectively. MAFs of rs1065852 (CYP2D6) and rs750155 (SULT1A1) showed the largest fluctuation between the BP and SAS, EUR, AFR and AMR populations.Conclusion: Our data can provide theoretical guidance for safe and efficacious personalized drug use in the Blang population.Keywords: Blang population, single-nucleotide polymorphism, SNP, very important pharmacogene, genotype distribution, pharmacogenomics, personalized drug use

Chunjuan He,1 Linna Peng,1 Shishi Xing,1 Dandan Li,1 Li Wang,1 Tianbo Jin1,2 1Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, 712082, People’s Republic of China; 2Key Laboratory for Basic Life Science Research of Tibet Autonomous Region, Xizang Minzu University, Xianyang, Shaanxi, 712082, People’s Republic of ChinaCorrespondence: Tianbo JinKey Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, #6, Wenhui East Road, Xianyang, 712082, Shaanxi, People’s Republic of ChinaTel/Fax +86-29-88895902Email jintianbo@gmail.comBackground: Genetic variation influences drug reaction or adverse prognosis. The purpose of this research was to genotype very important pharmacogenetic (VIP) variants in the Tibetan population.Methods and Materials: Blood samples from 200 Tibetans were randomly collected and 59 VIP variants were genotyped, and then compared our data to 26 other populations in the 1000 project to further analyze and identify significant difference.Results: The results showed that on comparing with most of the 26 populations from the 1000 project, rs4291 (ACE), rs1051296 (SLC19A1) and rs1065852 (CYP2D6) significantly differed in the Tibetan population. Furthermore, three significant loci were related to drug response. In addition, the allele frequency of Tibetans least differed from that of East Asian populations, and most differed from that of Americans.Conclusion: Three significant loci of variation ACE rs4291, SLC19A1 rs1051296 and CYP2D6 rs1065852 were associated with drug response. This result will contribute to improving the information of the Tibetan in the pharmacogenomics database, and providing a theoretical basis for clinical individualised drug use in Tibetans.Keywords: the Tibetan population, pharmacogenomics, VIP variants

Xiaoli Liu,1,* Linna Peng,1,* Dandan Li,1 Chunjuan He,1 Shishi Xing,1 Yuhe Wang,2 Yongjun He1 1Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, 712082, People’s Republic of China; 2Department of Clinical Laboratory, The Affiliated Hospital of Xizang Minzu University, Xianyang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yongjun HeKey Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, #6 East Wenhui Road, Xianyang, 712082, Shaanxi, People’s Republic of ChinaTel +86-18691008772Email 545139647@qq.comBackground: Rheumatoid arthritis (RA), an autoimmune systemic inflammatory disease, largely resulted from genetic factor. Our purpose was to explore the association for IL1R1 and IL1R2 genetic variants with RA susceptibility in the Chinese Han population.Patients and Methods: A total of 508 RA patients and 494 controls were involved in this case–control study; single-nucleotide polymorphisms (SNPs) genotyping was identified by the Agena MassARRAY platform. The relationship between polymorphisms and RA susceptibility was calculated using the Pearson’s Chi-square test with odds ratios and 95% confidence intervals (CIs) in multiple genetic models. The Pearson’s Chi-square test and Student’s t-test were used for sample basic characteristic analysis. And linkage disequilibrium (LD) analysis and haplotype analysis were performed by logistic regression analysis.Results: The result from this study showed that rs2072472 (IL1R2) was an increased risk factor of RA (adjusted OR = 1.41, p = 0.011). Stratified analysis indicated SNPs rs10490571, rs956730, rs3917318 of IL1R1, and SNPs rs4851527, rs719250, rs3218896, rs3218977, rs2072472 of IL1R2 had impacts on RA risk after stratification based on gender and average age (54 years). Finally, haplotype analysis revealed that Ars3218977Ars2072472 haplotype in IL1R2 was related to a decreased RA risk (adjusted OR = 0.79; 95% CI = 0.65– 0.94; p = 0.010). Yet, rs3917225(IL1R1) and rs11674595(IL1R2) were not significant in RA association analysis.Conclusion: We determined SNPs (rs3917318, rs956730, rs1049057) of IL1R1 and SNPs (rs3218977, rs719250, rs4851527, rs3218896, rs2072472) of IL1R2 were correlated with the RA susceptibility in the Chinese Han population.Keywords: rheumatoid arthritis, RA, IL1R1/IL1R2, single-nucleotide polymorphism, SNP, susceptibility

Baojia Zou,1,* Xialei Liu,1,* Yihang Gong,1,* Chaonong Cai,1 Peiping Li,1 Shan Xing,2 Bibesh Pokhrel,1 Baimeng Zhang,1 Jian Li1 1Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China; 2Department of Clinical Laboratory, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China *These authors contributed equally to this work Background/Aim: Cancer-associated fibroblasts (CAFs) are important factors in the progression of hepatocellular carcinoma (HCC). But the characterization of these cells remains incomplete. This study aims to identify a panel of markers for CAFs that are associated with HCC progression. Materials and methods: The sequencing data and clinicopathological characteristics of 366 patients were obtained from the Cancer Genome Atlas (TCGA) database (366 HCC tissues and there were 50/366 cases with corresponding normal liver tissues). In vitro validation of the markers was performed by quantitative real-time PCR using the hepatic stellate cell line LX2 induced by the HCC cell line Huh7. The activation of LX2 was confirmed by α-smooth muscle actin and fibroblast activation protein, using quantitative real-time PCR and immunofluorescence staining. In vivo detections of the 12 markers were done in 40 tissue samples (30 HCC and 10 normal). Results: We successfully identified 12 CAF markers from TCGA data: FGF5, CXCL5, IGFL2, MMP1, ADAM32, ADAM18, IGFL1, FGF8, FGF17, FGF19, FGF4, and FGF23. The 12-marker panel was associated with the pathological and clinical progressions of HCC. All 12 markers were upregulated in vitro. In vivo expressions of these markers were paralleled with those in TCGA data. Conclusion: A 12-marker panel of CAFs in HCC is identified, which is associated with both pathological and clinical progressions of cancer. Keywords: hepatocellular carcinoma, cancer-associated fibroblasts, CAFs marker panel, TCGA database analysis, transcriptome profiling

Since the initial research leading to the production of diamond composite materials, there have been several important developments leading to significant improvements in the properties of these superhard composite materials. Apart from the fact that diamonds, whether originating from natural resources or synthesised commercially, are the hardest and most wear-resistant materials commonly available, there are other mechanical properties that limit their industrial application. These include the low fracture toughness and low impact strength of diamond. By incorporating a range of binder phases into the sintering production process of these composites, these critically important properties have been radically improved. These new composites can withstand much higher operating temperatures without markedly reducing their strength and wear resistance. Further innovative steps are now being made to improve the properties of diamond composites by reducing grain and particle sizes into the nano range. This review will cover recent developments in diamond composite materials with special emphasis on microstructural characterisation. The results of such studies should assist in the design of new, innovative diamond tools as well as leading to radical improvements in the productivity of cutting, drilling and sawing operations in the exploration, mining, civil construction and manufacturing industries.

Impact abrasive wear behavior of high chromium white iron (HCWI) produced by liquid die forging process were investigated. the wear tests were performed with the MLD-10 abrasive wear testing machine, using SiO2 abrasive and with four impact energies of 1.5 J, 2.5 J, 3.5 J and 4.5 J for 120 min. The results indicated that the cumulative volume loss of HCWI sample increases with the growth of impact energy, and exhibits best wear resistance under low impact condition. For given impact energy, the volume loss increases with the increasing of wear time, which shown an approximately liner tendency. The macro-morphologies, SEM images of worn surface and cross-sectional images of wear samples were observed by optical microscope and SEM, and the wear mechanism and characteristics were analyzed. Results shown that the wear characteristics is mainly based on the shallow ploughing and accompanied by plastic deformation under lower impact energy, while the fatigue peeling and embedded abrasive become the most significant characteristics when the impact energy is higher.

Qian Yuan,&ast; Long-Wu Xiao,&ast; Yao Zhang, Long Li, Teng Xia, Qing Xu, Shi-Gui Xing, Liu-Shun Wang Department of Thoracic Surgery, Nan Jing Gaochun PEople’s Hospital (The Gaochun Affiliated Hospital of Jiang Su University), Nanjing, Jiangsu, 210000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shi-Gui Xing; Liu-Shun Wang, Email gcxw5988@163.com; lswang052066@sina.comBackground: Systemic immune-inflammation index (SII) is a novel comprehensive inflammatory marker. Inflammation is associated with impaired lung function. We aimed to explore the possible relationship between SII and lung function to examine the potential of SII in predicting lung function decline.Methods: A cross-sectional survey was conducted using the data of the NHANES from 2007 to 2012. Multiple linear regression models were used to analyze the linear relationship between SII and pulmonary functions. Sensitivity analyses, subgroup analyses, and interaction tests were used to examine the robustness of this relationship across populations. Fitted smooth curves and threshold effect analysis were used to describe the nonlinear relationships.Results: A total of 10,125 patients were included in this study. After adjusting for all covariates, multiple linear regression model analysis showed that high Log2-SII level was significantly associated with decreased FVC(β, − 23.4061; 95% CI, − 42.2805- − 4.5317), FEV1(β, − 46.7730; 95% CI, − 63.3371- − 30.2089), FEV1%(β, − 0.7923; 95% CI, − 1.1635- − 0.4211), FEV1/FVC(β, − 0.6366; 95% CI, − 0.8328- − 0.4404) and PEF(β, − 121.4468; 95% CI,-164.1939- − 78.6998). The negative correlation between Log2-SII and pulmonary function indexes remained stable in trend test and stratified analysis. Inverted U-shaped relationships between Log2-SII and FVC, FEV1, FEV1%, and PEF were observed, while a negative linear correlation existed between FEV1/FVC and Log2-SII. The cutoff values of the nonlinear relationship between Log2-SII and FVC, FEV1, FEV1%, PEF were 8.3736, 8.0688, 8.3745, and 8.5255, respectively. When SII exceeded the critical value, the lung function decreased significantly.Conclusion: This study found a close correlation between SII and pulmonary function indicators. This study investigated the SII threshold when lung functions began to decline in the overall population. SII may become a promising serological indicator for predicting lung function decline. However, prospective studies were needed further to establish the causal relationship between these two factors.Keywords: NHANES, population-based study, systemic immune-inflammation index, pulmonary function

Intrafraction motion management is crucial for accurate and safe delivery during spine SBRT. Currently, quantitative 3D motion tracking techniques using the on-board imager on a standard equipped Linac are limited. In this pilot study, we evaluate the efficacy of a pre-clinical real-time motion tracking system (RTTS) to quantitatively monitor the vertebral body during high dose (90 Gy) dorsal spinal nerve ablation SRS for patients with intractable back pain. This study is part of an IRB-approved phase-I protocol to deliver 90 Gy in a single fraction to ablate the involved dorsal nerve root ganglion. RTTS was evaluated using an anthropomorphic spine phantom placed on a programable one-dimensional motion platform at 30° from the longitudinal axis of the couch to generate a two-dimensional motion. The phantom was shifted 6 cm in 1 cm increments during the arc delivery, simulating a total lateral and longitudinal motion of 3 cm and 5.2 cm respectively. Fluoroscopic kilovoltage images were continuously acquired at 2 frames/s. A set of digitally reconstructed radiographs of the target vertebra, which served as a template for triangulating the target positions in three dimensions, was generated from the planning CT at 1° gantry angle resolution. After each shift, clinical standards, CBCT and stereoscopic kV-images (SKV), were acquired to compare with the RTTS results. Tracking accuracy was further evaluated in a pilot study that included six spine SBRT patients. CBCT projections were used to triangulate the target positions instead of fluoroscopic images to avoid deviation from the current clinical protocol. The average positional offset and standard deviation (SD) were evaluated against the measured clinical shifts after CBCT in all three directions. In our phantom study, the mean offset measured with RTTS was within 0.2 ± 0.1 mm of the simulated shifts, with a maximum deviation of 0.3mm and 0.4mm in the lateral and longitudinal directions respectively. The positional offsets determined by RTTS agreed with the CBCT-based shifts, within 0.1 ± 0.1 mm laterally and 0.2 ± 0.2 mm longitudinally. The tracking accuracy of RTTS is also similar to that of the SKV system, where an average difference of 0.1 ± 0.1mm from the simulated shifts were observed in both directions. Six SBRT patients with two C-spine, T-spine and L-spine lesions were included in our pilot study. The average lateral, longitudinal and vertical shifts measured by RTTS were within 0.2 ± 0.1 mm, 0.2 ± 0.1 mm and 0.1 ± 0.1 mm difference from the CBCT-based shifts, with a maximum deviation of 0.3mm in the lateral/longitudinal directions and 0.2mm in the vertical direction. Our preliminary results demonstrate that RTTS quantitatively monitors positional change of the vertebral body during beam delivery. The target position measured by RTTS is consistent with the CBCT-and SKV-based positions, suggesting RTTS as a potential alternative for intrafraction motion monitoring during spine radiosurgery. [ABSTRACT FROM AUTHOR]

Selective engineering of the interface between nanoscale components and the electrical properties of heterojunctions is key to the development of next-generation nanoscale circuit elements. In this paper, we show how laser processing of a metal-P type semiconductor nanoscale heterojunction between Ag and CuO nanowires can be used to control the nature of the electrical contact by reducing the Schottky barrier at the Ag–CuO interface to Ohmic contact. Elimination of the Schottky barriers occurs in response to lattice matching of Ag(111)∥CuO(111) planes at the interface induced by controlled irradiation with femtosecond (fs) laser pulses. An interdiffusion region with a mixed Ag/CuO composition is also present over a localized area of the interface between the Ag and CuO nanowires after fs laser processing, but both Ag and CuO nanowires remain crystalline away from the heterojunction. In addition, the Ag nanowire becomes totally embedded in the larger CuO nanowire after irradiation. Fabricated nanowire devices from Ag–CuO nanowire heterojunctions transition from a double-Schottky contact configuration prior to laser processing to a rectifying behavior as irradiation time increases. This study illustrates that fs laser processing can be highly effective in the engineering of electrical performance in metal–semiconductor nanoscale heterojunction devices. [ABSTRACT FROM AUTHOR]

Peptides, as small molecular compounds, exhibit prominent advantages in the inhibition of coronaviruses due to their safety, efficacy, and specificity, holding great promise as drugs against coronaviruses. The rapid and efficient determination of the activity of anti-coronavirus peptides (ACovPs) can greatly accelerate the development of drugs for treating coronavirus-related diseases. Hence, we present ACVPICPred, a computational model designed to predict the inhibitory activity of ACovPs based on their sequences and structural information. By leveraging bioinformatics tools AlphaFold3 for structural predictions and several feature extraction methods, the model integrates both sequence and structural features to enhance prediction accuracy. To address the limitations of existing datasets, we employed data augmentation techniques, including the introduction of noise and the SMOGN, to improve the model robustness. The model’s performance was evaluated through five-fold cross-validation, achieving a Pearson correlation coefficient of 0.7668 (p

Background: Preterm premature rupture of membranes (PPROM) contributes to over one-third of preterm births, and PPROM infants are more susceptible to infections. However, the risk factors remain poorly understood. We here aim to investigate the association of duration of premature rupture of membranes (PROM) and environmental microbiota with the gut microbiota and infection in PPROM infants. Methods: Forty-six premature infants were recruited from two hospitals, and infant fecal and environmental samples were collected. 16 s rRNA sequencing was performed to analyze the fecal and environmental microbiome. Human inflammatory cytokines in cord vein plasma were measured. Results: The gut microbiota composition of PPROM infants was different from that of non-PPROM infants, and the microbiome phenotypes were predicted to be associated with a higher risk of infection, further evidenced by the significantly increased levels of IL-6 and IL-8 in cord vein plasma of PPROM infants. The diversity of the gut microbiota in PPROM infants increased significantly as the duration of PROM excessed 12 h, and Pseudomonas contributed significantly to the dynamic changes. The Pseudomonas species in the gut of PPROM infants were highly homologous to those detected in the ward environment, suggesting that prolonged PROM is associated with horizontal transmission of environmental pathogens, leading to a higher risk of infection. Conclusions: This study highlights that the duration of PROM is associated with the accumulation of environmental pathogens in the gut of PPROM infants, which is a risk factor for nosocomial infections. Improving environmental hygiene could be effective in optimizing the clinical care of PPROM infants.

Laser peen forming (LPF) is an appealing technique for forming metal sheets using high-energy, short-duration laser pulses. The deformation of the target metal plate is closely related to the magnitude and distribution of laser-induced residual stress. Consequently, the relationship between process parameters and residual stress is worth researching. In this research, two process parameters in LPF, laser energy and coverage ratio (spot distance essentially), and one workpiece parameter, plate thickness, were examined through an element method (FEM) of multiple square-spot laser shock peening (SSLSP). Corresponding experiments of SSLSP on aluminum alloy 2024-T351 test blocks were conducted, together with an X-ray diffraction (XRD) residual stress measurement and a surface morphology observation. The FEM simulation and experimental results show that congested laser spots had a significant influence on the magnitude of compressive residual stress; higher laser energy was beneficial to the depth of the compressive stress layer but could decrease its magnitude. Therefore, for better forming ability, higher laser energy and a higher coverage ratio are beneficial; for surface strengthening, laser energy should not be too large, and the coverage ratio should be larger than 100% to ensure that the residual stress on the treated surface is compressive, resulting in better surface integrity.

Abstract Alkaline hydrogen evolution reaction (HER) for scalable hydrogen production largely hinges on addressing the sluggish bubble‐involved kinetics on the traditional Ni‐based electrode, especially for ampere‐level current densities and beyond. Herein, 3D‐printed Ni‐based sulfide (3DPNS) electrodes with varying scaffolds are designed and fabricated. In situ observations at microscopic levels demonstrate that the bubble escape velocity increases with the number of hole sides (HS) in the scaffolds. Subsequently, we conduct multiphysics field simulations to illustrate that as the hole shapes transition from square, pentagon, and hexagon to circle, where a noticeable reduction in the bubble‐attached HS length and the pressure balance time around the bubbles results in a decrease in bubble size and an acceleration in the rate of bubble escape. Ultimately, the 3DPNS electrode with circular hole configurations exhibits the most favorable HER performance with an overpotential of 297 mV at the current density of up to 1000 mA cm−2 for 120 h. The present study highlights a scalable and effective electrode scaffold design that promotes low‐cost and low‐energy green hydrogen production through the ampere‐level alkaline HER.

Abstract Optoelectronic neural interfaces can leverage the photovoltaic effect to convert light into electrical current, inducing charge redistribution and enabling nerve stimulation. This method offers a non-genetic and remote approach for neuromodulation. Developing biodegradable and efficient optoelectronic neural interfaces is important for achieving transdermal stimulation while minimizing infection risks associated with device retrieval, thereby maximizing therapeutic outcomes. We propose a biodegradable, flexible, and miniaturized silicon-based neural interface capable of transdermal optoelectronic stimulation for neural modulation and nerve regeneration. Enhancing the device interface with thin-film molybdenum significantly improves the efficacy of neural stimulation. Our study demonstrates successful activation of the sciatic nerve in rodents and the facial nerve in rabbits. Moreover, transdermal optoelectronic stimulation accelerates the functional recovery of injured facial nerves.

Abstract Harmonic resonance is caused by harmonic source matching resonance frequency and presents the characteristics of decentralization and whole network in modern grids. The current resonance suppression methods mainly focus on reducing the harmonic source, and are suitable for single‐site and small‐scale grids. This paper presents a new method for suppressing parallel resonance at system level. The holistic harmonic resonance is suppressed by reducing the harmonic impedance. In addition, new resonances are prevented by weakening the coupling between resonance and non‐resonance frequencies. The resonance modal analysis and resonance frequency shift (RFS) are employed to optimize harmonic impedance. Simulation results indicate that the capacitance parameter has higher sensitivity and is theoretically more suitable for RFS. Considering the accuracy of modal frequency sensitivity, a variable‐limit genetic algorithm for iteration is proposed. The validity of the proposed method was verified using an IEEE 14‐bus test network.

Abstract Conducting polymer hydrogel can address the challenges of stricken biocompatibility and durability. Nevertheless, conventional conducting polymer hydrogels are often brittle and weak due to the intrinsic quality of the material, which exhibits viscoelasticity. This property may cause a delay in sensor response time due to hysteresis. To overcome these limitations, we have designed a wrinkle morphology three‐dimensional (3D) substrate using digital light processing technology and then followed by in situ polymerization to form interpenetrating polymer network hydrogels. This novel design results in a wrinkle morphology conducting polymer hydrogel elastomer with high precision and geometric freedom, as the size of the wrinkles can be controlled by adjusting the treating time. The wrinkle morphology on the conducting polymer hydrogel effectively reduces its viscoelasticity, leading to samples with quick response time, low hysteresis, stable cyclic performance, and remarkable resistance change. Simultaneously, the 3D gradient structure augmented the sensor's sensitivity under minimal stress while exhibiting consistent sensing performance. These properties indicate the potential of the conducting polymer hydrogel as a flexible sensor.

Abstract In areas where loess is distributed, landslides represent a significant geohazard with severe implications. Among these events, loess-mudstone landslides are particularly prevalent, posing substantial risks to the safety and property of local residents, and moisture plays a pivotal role as a key factor in causing these disasters. In this study, the hydraulic properties of the soils along the longitudinal section of an ongoing loess-mudstone landslide are investigated through the variation of soil water characteristic curves, which are subsequently fitted by utilizing van Genuchten model. Moreover, a comprehensive experimental investigation was conducted on the loess, mudstone, and loess-mudstone mixtures to facilitate analysis, including X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM) observation, particle size distribution (PSD) analysis, along with fundamental geotechnical tests for parameter determination. It is found that mudstone and loess have distinct SWCC distribution. The SWCC of loess at various depths exhibits a similar distribution pattern due to the occurrence of landslide. The SWCC distribution of loess-mudstone mixture displays a transitional trend between the SWCC of mudstone and that of loess, and the water retention capacity increases as the mudstone content increases. The experimental findings have demonstrated notable agreement between each other and exhibited a satisfactory level of concurrence with the observed phenomena in geological surveys.

ABSTRACT Phage-antibiotic synergy (PAS) represents a superior treatment strategy for pathogen infections with less probability of resistance development. Here, we aim to understand the molecular mechanism by which PAS suppresses resistance in terms of population evolution. A novel hypervirulent Klebsiella pneumoniae (KP) phage H5 was genetically and structurally characterized. The combination of H5 and ceftazidime (CAZ) showed a robust synergistic effect in suppressing resistance emergence. Single-cell Raman analysis showed that the phage-CAZ combination suppressed bacterial metabolic activities, contrasting with the upregulation observed with phage alone. The altered population evolutionary trajectory was found to be responsible for the contrasting metabolic activities under different selective pressures, resulting in pleiotropic effects. A pre-existing wcaJ point mutation (wcaJG949A) was exclusively selected by H5, conferring a fitness advantage and up-regulated activity of carbohydrate metabolism, but also causing a trade-off between phage resistance and collateral sensitivity to CAZ. The wcaJ point mutation was counter-selected by H5-CAZ, inducing various mutations in galU that imposed evolutionary disadvantages with higher fitness costs, and suppressed carbohydrate metabolic activity. H5 and H5-CAZ treatments resulted in opposite effects on the transcriptional activity of the phosphotransferase system and the ascorbate and aldarate metabolism pathway, suggesting potential targets for phage resistance suppression. Our study reveals a novel mechanism of resistance suppression by PAS, highlighting how the complexity of bacterial adaptation to selective pressures drives treatment outcomes.IMPORTANCEPhage-antibiotic synergy (PAS) has been recently proposed as a superior strategy for the treatment of multidrug-resistant pathogens to effectively reduce bacterial load and slow down both phage and antibiotic resistance. However, the underlying mechanisms of resistance suppression by PAS have been poorly and rarely been studied. In this study, we tried to understand how PAS suppresses the emergence of resistance using a hypervirulent Klebsiella pneumoniae (KP) strain and a novel phage H5 in combination with ceftazidime (CAZ) as a model. Our study reveals a novel mechanism by which PAS drives altered evolutionary trajectory of bacterial populations, leading to suppressed emergence of resistance. The findings advance our understanding of how PAS suppresses the emergence of resistance, and are imperative for optimizing the efficacy of phage-antibiotic therapy to further improve clinical outcomes.

ObjectiveAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by increasing prevalence, diverse impairments, and unclear origins and mechanisms. To gain a better grasp of the origins of ASD, it is essential to identify the most distinctive structural brain abnormalities in individuals with ASD.MethodsA Multi-Stage Progressive Feature Refinement Approach was employed to identify the most pivotal structural magnetic resonance imaging (MRI) features that distinguish individuals with ASD from typically developing (TD) individuals. The study included 175 individuals with ASD and 69 TD individuals, all aged between 7 and 18 years, matched in terms of age and gender. Both cortical and subcortical features were integrated, with a particular focus on hippocampal subfields.ResultsOut of 317 features, 9 had the most significant impact on distinguishing ASD from TD individuals. These structural features, which include a specific hippocampal subfield, are closely related to the brain areas associated with the reward system.ConclusionStructural irregularities in the reward system may play a crucial role in the pathophysiology of ASD, and specific hippocampal subfields may also contribute uniquely, warranting further investigation.