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Yi Guo, Yong-Gen Zhang, Hong-Chun Li, Yin-Hai Xu Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of ChinaCorrespondence: Yin-Hai XuDepartment of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, Jiangsu, 221002, People’s Republic of ChinaTel +8618705201189Email xyfyxyh@126.comPurpose: Most patients diagnosed with extrahepatic cholangiocarcinoma (ECCA) exhibit cholestasis caused by obstruction of the bile duct. Cholestasis is associated with lipid disorders, but studies focused on the changing lipid parameters in patients with ECCA are lacking. Here, we observed lipid profiles in patients with ECCA and investigated whether the removal of biliary obstruction could correct dyslipidemia.Patients and Methods: We consecutively included patients admitted to the hepatobiliary surgery department at the Affiliated Hospital of Xuzhou Medical University. The patients were divided into an ECCA group or a non-ECCA group based on the disease assessment. Patients with histological confirmation of ECCA were included in the ECCA group. Blood samples were collected on admission as well as five days after treatment. An automatic biochemistry analyzer was used to test liver function and serum lipid levels. Serum lipoprotein electrophoresis was performed using barbitone sodium buffer and Sudan black B.Results: A total of 180 patients met inclusion criteria and were enrolled for this study. Of these, 76 patients were diagnosed with ECCA; all other patients were enrolled in the non-ECCA group. Total cholesterol (TC) and small and dense low-density lipoprotein cholesterol (sdLDL-C) levels were significantly elevated in the ECCA group. LDL-C levels were found to be slightly lower in the ECCA group. In the ECCA group, serum samples were detained in sample wells and lipoproteins failed to be separated. TC and sdLDL-C levels significantly decreased after cholestasis relief in the ECCA group. Lipoprotein electrophoresis revealed that patients with ECCA showed normal lipoprotein patterns after treatment.Conclusion: Patients with ECCA exhibited transiently elevated TC and sdLDL-C levels and falsely low LDL-C results. TC, sdLDL-C, and LDL-C levels could be restored to normal levels after biliary obstruction removal and cholestasis relief.Keywords: extrahepatic cholangiocarcinoma, cholestasis, dyslipidemia, TC, LDL-C, sdLDL-C

Xinzhe Yu,1,* Yang Di,2,* Chao Xie,3 Yunlong Song,4 Hang He,2 Hengchao Li,1 Xinming Pu,5 Weiyue Lu,3 Deliang Fu,2 Chen Jin1 1Pancreatic Surgery Department, Huashan Hospital, 2Pancreatic Disease Institute, Fudan University, 3School of Pharmacy & Key Laboratory of Smart Drug Delivery, Fudan University, 4School of Pharmacy, The Second Military Medical University, 5The State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background and objectives: Gemcitabine (Gem) is far from satisfactory as the first-line regimen for pancreatic cancer, and the emergence of albumin nanoparticles offers new hope for the delivery of Gem. In this study, Gem-loaded human serum albumin nanoparticles (Gem-HSA-NPs) were successfully synthesized, characterized, and tested on a BxPC-3 cell line both in vitro and in vivo.Materials and methods: 4-N-myristoyl-gemcitabine (Gem-C14) was obtained first by coupling myristoyl with the 4-amino group of Gem. The Gem-HSA-NPs were then prepared by nanoparticle albumin-bound technology and characterized for particle size, zeta potential, morphology, encapsulation efficiency, drug-loading efficiency, and release characteristics. Using both in vitro and in vivo studies, Gem-C14 and Gem-HSA-NPs were tested on the human pancreatic cancer cell line BxPC-3.Results: Gem-HSA-NPs showed an average particle size of 150±27 nm, and with an encapsulation rate of 82.99%±3.5% and a drug-loading rate of 10.42%±3.5%, they exhibited a favorable controlled- and sustained-release nature. In in vitro, Gem-C14 was equivalent in cytotoxicity to Gem. In in vivo, the Gem-HSA-NPs exhibited the strongest inhibitory effect on tumor growth but the lowest toxicity among the four groups.Conclusion: The enhanced in vivo efficacy of Gem-HSA-NPs toward the pancreatic cancer cell line suggests their potential role for use in the clinical field. Keywords: pancreatic cancer, gemcitabine, albumin nanoparticles, BxPC-3 cell line, in vitro study, in vivo study

In Taiwan, despite a substantial decline of Salmonella enterica serotype Choleraesuis infections, strains resistant to ciprofloxacin and ceftriaxone persist. A self-transferable bla(CMY-2)-harboring IncI1 plasmid was identified in S. enterica serotypes Choleraesuis, Typhimurium, Agona, and Enteritidis and contributed to the overall increase of ceftriaxone resistance in salmonellae. [ABSTRACT FROM AUTHOR]

PURPOSE. This paper aims to examine the effectiveness and appropriateness of using therapeutic play in preparing children for surgery. DESIGN/METHOD. A randomized controlled trial was employed. Children (7-12 years of age; n = 203) admitted for surgery during a 13-month period were recruited. RESULTS. The results support the effectiveness and appropriateness of using therapeutic play in preparing children for surgery. PRACTICE IMPLICATIONS. The study results promote awareness in nurses and parents that play is a very important part of children's lives, and heighten the importance of integrating therapeutic play as an essential component of holistic and quality nursing care to prepare children for surgery. [ABSTRACT FROM AUTHOR]

Amidst far-reaching COVID-19 effects and social constraints, this study leveraged wastewater-based epidemiology to track 38 conventional drugs and 30 new psychoactive substances (NPS) in northern Taiwan. Analyzing daily samples from four Taipei wastewater plants between September 2021 and January 2024-encompassing club reopenings, holidays, Lunar New Year, an outbreak, and regular periods-thirty-one drugs were detected, including 5 NPS. Tramadol, zolpidem tartrate, CMA, and MDPV were newly detected in Taiwanese sewage with frequency of 1.4 %- 89.0 %. Conventional drug use typically increased post-pandemic, aside from benzodiazepines and methadone. Methamphetamine showed 100 % frequency, indicating ongoing daily consumption despite COVID-19 measures. Methamphetamine and morphine's consumption dipped then rose around club reopening, hinting at limited access. The consumption trend of methadone appeared to compensate for the use of morphine. Ketamine and NPS demonstrated similar patterns throughout the entire period. NPS as party drugs seemed influenced by an unstable supply chain and complexities in implementation. Benzodiazepines, commonly abused alongside synthetic cathinones in Taiwan exhibited an opposing trend to NPS while aligned with acetaminophen, suggesting elevated stress and anxiety levels during the pandemic. No significant differences were observed in drug consumption between weekdays and weekends, potentially indicating that COVID-19 measures blurred the traditional distinctions between these timeframes. ENVIRONMENTAL IMPLICATION: New psychoactive substances refer to chemically modified variants of controlled drugs designed to mimic the effects of the original drugs while evading modern detection methods, categorizing them as hazardous materials. The study presents a sewage monitoring project conducted from 2021 to 2024, collecting samples from four WWTPs to analyze NPS and conventional drug trends during and after the COVID-19 pandemic. The findings uncovered connections between drug consumption patterns and pandemic-related policies. In light of the persistent drug abuse and their environmental presence, the results bear critical importance for both environmental and public health. We provide a thorough assessment of these relationships and prioritize areas for future research., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Pai-Shan Chen reports financial support was provided by National Science and Technology Council., (Copyright © 2024 Elsevier B.V. All rights reserved.)

X-ray photoelectron spectroscopy, reflection-absorption infrared spectroscopy, and temperature-programmed reaction/desorption have been employed to investigate the reaction of CH3-CHCl-C(=O)Cl on Cu (100), with the aid of density functional theory (DFT) calculations. Experimentally, CH3-CH=C=O (methylketene) is found to be the product from the dechlorination of CH3-CHCl-C(=O)Cl on Cu(100) at 120 K. The CH3-CH=C=O generated on the surface would dimerize to form 2,4-dimethylcyclobutane-1,3-dione below 180 K. In agreement with the experimental findings, our DFT molecular dynamics simulations demonstrate that the dechlorination of CH3-CHCl-C(=O)Cl, resulting in CH3-CH=C=O and two Cl atoms, occurs readily, completing within 0.6 ps at 300 K. The simulations also indicate that the cleavage of the CH-Cl bond precedes that of the C(=O)-Cl bond. The static DFT calculations suggest that the dimerization of CH3-CH=C=O primarily occurs through the coupling of two C=C bonds, which has a lower barrier of 38.08 kJ mol-1 compared to the 69.05 kJ mol-1 barrier for C=C + C=O coupling., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

In April 2024, the World Health Organization/International Agency for Research on Cancer (IARC) published the global cancer statistics 2022 in the CA : Cancer Journal for Clinicians . This report focuses on the incidence and mortality of 36 cancers in 185 countries or territories worldwide, analyzing the differences of gender, geographic region, and the Human Development Index (HDI) level. It is estimated that in the year 2022, there were 19.96 million new cancer cases and 9.74 million cancer deaths worldwide. Lung cancer (2 480 301, 12.4%) was the most frequently diagnosed cancer in 2022, followed by female breast cancer (2 295 686, 11.5%), colorectal cancer (1 926 118, 9.6%), prostate cancer (1 466 680, 7.3%), and gastric cancer (968 350, 4.9%). Lung cancer (1 817 172, 18.7%) was also the leading cause of cancer death, followed by colorectal cancer (903 859, 9.3%), liver cancer (757 948, 7.8%), female breast cancer (665 684, 6.9%), and gastric cancer (659 853, 6.8%). With demographics-based predictions indicating that the number of new cases of cancer will reach over 35 million by 2050. The Beijing Office for Cancer Prevention and Control team has collated this report and briefly interpreted it in combination with the current situation of cancer incidence and mortality in China.

Nonstructural carbohydrates (NSC) are essential for tree growth and adaptation, yet our understanding of the seasonal storage and mobilization dynamics of whole-tree NSC is still limited, especially when tree functional types are involved. Here, Quercus acutissima Carruth. and Pinus massoniana Lamb, with distinct life-history traits (i.e. a deciduous broadleaf species vs an evergreen coniferous species), were studied to assess the size and seasonal fluctuations of organ and whole-tree NSC pools with a focus on comparing differences in carbon resource mobilization patterns between the two species. We sampled the organs (leaf, branch, stem and root) of the target trees repeatedly over four seasons of the year. Then, NSC concentrations in each organ were paired with biomass estimates from the allometric model to generate whole-tree NSC pools. The seasonal dynamics of the whole-tree NSC of Q. acutissima and P. massoniana reached the peak in autumn and summer, respectively. The starch pools of the two species were supplemented in the growing season while the soluble sugar pools were the largest in the dormant season. Seasonal dynamics of organ-level NSC concentrations and pools were affected by organ type and tree species, with above-ground organs generally increasing during the growing season and P. massoniana roots decreasing during the growing season. In addition, the whole-tree NSC pools of P. massoniana were larger but Q. acutissima showed larger seasonal fluctuations, indicating that larger storage was not associated with more pronounced seasonal fluctuations. We also found that the branch and root were the most dynamic organs of Q. acutissima and P. massoniana, respectively, and were the major suppliers of NSC to support tree growth activities. These results provide fundamental insights into the dynamics and mobilization patterns of NSC at the whole-tree level, and have important implications for investigating environmental adaptions of different tree functional types., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Objectives: We investigated the genetic diversities and lineage-specific transmission dynamics of multidrug-resistant tuberculosis (MDR-TB), with the goal of determining the potential factors driving the MDR epidemics in China., Methods: We curated a large nationwide Mycobacterium tuberculosis ( M. tuberculosis ) whole genome sequence data set, including 1313 MDR strains. We reconstructed the phylogeny and mapped the transmission networks of MDR-TB across China using Bayesian inference. To identify drug-resistance variants linked to enhanced transmissibility, we employed ordinary least-squares (OLS) regression analysis., Result: The majority of MDR-TB strains in China belong to lineage 2.2.1. Transmission chain analysis has indicated that the repeated and frequent transmission of L2.2.1 plays a central role in the establishment of MDR epidemic in China, but no occurrence of a large predominant MDR outbreak was detected. Using OLS regression, the most common single nucleotide polymorphisms (SNPs) associated with resistance to isoniazid ( katG_p.Ser315Thr and katG_p.Ser315Asn ) and rifampicin ( rpoB_p.Ser450Leu , rpoB_p.His445Tyr , rpoB_p.His445Arg , rpoB_p.His445Asp , and rpoB_p.His445Asn ) were more likely to be found in L2 clustered strains. Several putative compensatory mutations in rpoA , rpoC , and katG were significantly associated with clustering. The eastern, central, and southern regions of China had a high level of connectivity for the migration of L2 MDR strains throughout the country. The skyline plot showed distinct population size expansion dynamics for MDR-TB lineages in China., Conclusion: MDR-TB epidemic in China is predominantly driven by the spread of highly transmissible Beijing strains. A range of drug-resistance mutations of L2 MDR-TB strains displayed minimal fitness costs and may facilitate their transmission.

Multisource remote sensing data classification is a challenging research topic, and how to address the inherent heterogeneity between multimodal data while exploring their complementarity is crucial. Existing deep learning models usually directly adopt feature-level fusion designs, most of which, however, fail to overcome the impact of heterogeneity, limiting their performance. As such, a multimodal joint classification framework, called global clue-guided cross-memory quaternion transformer network (GCCQTNet), is proposed for multisource data i.e., hyperspectral image (HSI) and synthetic aperture radar (SAR)/light detection and ranging (LiDAR) classification. First, a three-branch structure is built to extract the local and global features, where an independent squeeze-expansion-like fusion (ISEF) structure is designed to update the local and global representations by considering the global information as an agent, suppressing the negative impact of multimodal heterogeneity layer by layer. A cross-memory quaternion transformer (CMQT) structure is further constructed to model the complex inner relationships between the intramodality and intermodality features to capture more discriminative fusion features that fully characterize multimodal complementarity. Finally, a cross-modality comparative learning (CMCL) structure is developed to impose the consistency constraint on global information learning, which, in conjunction with a classification head, is used to guide the end-to-end training of GCCQTNet. Extensive experiments on three public multisource remote sensing datasets illustrate the superiority of our GCCQTNet with regards to other state-of-the-art methods.

Introduction: Cervical cancer (CC) ranks as the fourth most prevalent malignant tumor among women worldwide, and is the fourth leading cause of cancer-related mortality. GuiErBai (GEB), a compound preparation developed by our research team, is derived from the ancient Chinese medicine of the Miao nationality and is comprised of podophyllotoxin (PTOX), imperatorin, isoimperatorin, and A. dahurica alkaloids. These individual components have demonstrated notable efficacy in tumor treatment. However, the specific anti-tumor effect of the compound Chinese medicine GEB in the context of CC has yet to be validated. Methods: HeLa and SiHa cell lines were utilized for in vitro experiments and treated with 5 mg/mL and 10 mg/mL GEB concentrations, respectively. The cell cycle changes after GEB treatment were assessed using flow cytometry. Transmission electron microscopy was employed to observe autophagic bodies and apoptotic bodies, while MDC staining evaluated the occurrence of autophagy. CCK-8 was used to observe the effect of GEB on cell proliferation, and Transwell assays assessed cell migration and invasion. Western blotting detected cell cycle and apoptosis-related protein expression, along with the expression level of autophagy-related protein LC3I/II. Changes in ROS and mitochondrial membrane potential in cervical cancer cells following GEB treatment were determined using ROS detection and mitochondrial membrane potential detection kits. For the in vivo experiment, a nude mouse model of cervical cancer transplantation based on HeLa cells was established. Experimental animals were divided into negative control, positive control, high-dose GEB (10 mg/mL), and low-dose GEB (5 mg/mL) groups. Results: In HeLa and SiHa cell lines, the G0/G1 phase of tumor cells significantly decreased ( p < 0.001), while the G2/M phase increased notably ( p < 0.001) following various GEB treatments. Electron microscopy showed GEB promoted apoptotic body and autophagosome formation in both cell lines. Compared to untreated HeLa and SiHa cells, GEB-treated cells exhibited significantly reduced caspase3 protein expression, and substantially increased autophagy-related protein LC3I/II expression. GEB treatment significantly reduced migration and invasion capabilities in both cell lines ( p < 0.001), while ROS content and mitochondrial membrane potential were significantly elevated ( p < 0.001). GEB effectively inhibited cervical cancer cell proliferation, with the optimal concentration being 10 mg/mL. A successful nude mouse model of cervical cancer transplantation was established using HeLa cells. Post-GEB treatment, the tumor volume and weight in nude mice significantly decreased ( p < 0.001), with diminished expression of CD34, VEGF, and caspase3 proteins in tumor tissues. Discussion: GEB exhibits a robust antitumor effect against cervical cancer, both in vitro and in vivo , in a concentration-dependent manner, by regulating autophagy and apoptosis of tumor cells., 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 Qin, Peng, Xu, Zhang, Tian, Wan, Pu, Li, Wu, Zheng and Xu.)

Objective: This study aims to examine the impact of PE/PPE gene mutations on the transmission of Mycobacterium tuberculosis (M. tuberculosis) in China., Methods: We collected the whole genome sequencing (WGS) data of 3202 M. tuberculosis isolates in China from 2007 to 2018 and investigated the clustering of strains from different lineages. To evaluate the potential role of PE/PPE gene mutations in the dissemination of the pathogen, we employed homoplastic analysis to detect homoplastic single nucleotide polymorphisms (SNPs) within these gene regions. Subsequently, logistic regression analysis was conducted to analyze the statistical association., Results: Based on nationwide M. tuberculosis WGS data, it has been observed that the majority of the M. tuberculosis burden in China is caused by lineage 2 strains, followed by lineage 4. Lineage 2 exhibited a higher number of transmission clusters, totaling 446 clusters, of which 77 were cross-regional clusters. Conversely, there were only 52 transmission clusters in lineage 4, of which 9 were cross-regional clusters. In the analysis of lineage 2 isolates, regression results showed that 4 specific gene mutations, PE4 (position 190,394; c.46G > A), PE&#95;PGRS10 (839,194; c.744 A > G), PE16 (1,607,005; c.620T > G) and PE&#95;PGRS44 (2,921,883; c.333 C > A), were significantly associated with the transmission of M. tuberculosis. Mutations of PE&#95;PGRS10 (839,334; c.884 A > G), PE&#95;PGRS11 (847,613; c.1455G > C), PE&#95;PGRS47 (3,054,724; c.811 A > G) and PPE66 (4,189,930; c.303G > C) exhibited significant associations with the cross-regional clusters. A total of 13 mutation positions showed a positive correlation with clustering size, indicating a positive association. For lineage 4 strains, no mutations were found to enhance transmission, but 2 mutation sites were identified as risk factors for cross-regional clusters. These included PE&#95;PGRS4 (338,100; c.974 A > G) and PPE13 (976,897; c.1307 A > C)., Conclusion: Our results indicate that some PE/PPE gene mutations can increase the risk of M. tuberculosis transmission, which might provide a basis for controlling the spread of tuberculosis., (© 2024. The Author(s).)

Despite recent therapeutic advances, ethnic minorities in the U.S. continue to have disproportionately poor outcomes in many hematologic malignancies including AML. We identified 162 adult AML patients treated at a non-transplant safety net hospital from 2007 to 2022 and evaluated differences in disease characteristics, treatment and clinical outcomes based on race and ethnicity. Our cohort consisted of 82 (50.6%) Hispanic, 36 (22.2%) non-Hispanic black and 44 (27.2%) non-Hispanic white and Asian patients. Median age at diagnosis was 42.5, 49.0 and 52.5 years respectively (p=0.025). Hispanics had higher rates of intermediate and high-risk disease (p=0.699) and received high intensity induction and consolidation chemotherapy at lower rates (p=0.962), although differences did not reach statistical significance. Despite this, similar remission rates were achieved. Hispanics with high-risk disease had longer overall survival (OS) than the combined non-Hispanic cohort (mOS 14 m vs 7 m, p=0.030). Multivariate regression analysis showed that OS was negatively associated with age (HR 1.023, p=0.006), intermediate (HR 3.431, p=0.0003) and high-risk disease (HR 4.689, p<0.0001) and positively associated with Hispanic ethnicity (HR 0.614, p=0.026). This report suggests that contrary to other studies, Hispanics, particularly those with high-risk AML, may have improved OS compared to other ethnic groups. These results are unique to our safety net hospital setting where common barriers to medical care and healthcare disparities are largely mitigated., Competing Interests: Declaration of Competing Interest YFM has received honoraria/consulting fees from BMS, Kura Oncology, BluePrint Medicines, Geron, OncLive and MD Education, VJHemOnc and Medscape Live. YFM participated in advisory boards and received honoraria from Sierra Oncology, Stemline Therapeutics, Blueprint Medicines, Morphosys, Taiho Oncology, SOBI, Rigel Pharmaceuticals, Geron, Cogent Biosciences and Novartis. YFM received travel reimbursement from Blueprint Medicines, MD Education, and Morphosys. None of these relationships were related to this work., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A range of recombinant monoclonal antibodies (rMAbs) have found application in treating diverse diseases, spanning various cancers and immune system disorders. Chinese hamster ovary (CHO) cells have emerged as the predominant choice for producing these rMAbs due to their robustness, ease of transfection, and capacity for posttranslational modifications akin to those in human cells. Transient transfection and/or stable expression could be conducted to express rMAbs in CHO cells. To bolster the yield of rMAbs in CHO cells, a multitude of approaches have been developed, encompassing vector optimization, medium formulation, cultivation parameters, and cell engineering. This review succinctly outlines these methodologies when also addressing challenges encountered in the production process, such as issues with aggregation and fucosylation., Competing Interests: Dr. Shih-Yen Lo, an editorial board member at Tzu Chi Medical Journal, had no role in the peer review process or the decision to publish this article. The other authors declared no conflicts of interest in writing this paper., (Copyright: © 2024 Tzu Chi Medical Journal.)

Objective: to analyse the differences in malnutrition assessment between the Global Leadership Initiative on Malnutrition (GLIM) criteria and the Patient-Generated Subjective Global Assessment (PG-SGA) among patients with hepatobiliary and pancreatic malignancies., Method: this study was a cross-sectional study and included 126 hospitalised patients who underwent surgery for hepatobiliary and pancreatic malignancies between November 1, 2019 and August 1, 2020. The patients' clinical data were collected, and malnutrition assessments were completed using the different nutritional assessment tools. The consistency of both tools was analysed using Cohen's kappa coefficient., Results: the prevalence of malnutrition showed a difference in diagnosis results between the GLIM criteria (36.51 %) and the PG-SGA (55.56 %). The two methods had moderate consistency (kappa = 0.590, p < 0.01). The sensitivity of a malnutrition diagnosis using a combination of GLIM and PG-SGA was 65.7 % (53.3 % and 76.4 %, respectively), and specificity was 100 % (92 % and 100 %, respectively). When malnutrition was evaluated using only PG-SGA, sensitivity was 88.9 % (95 % confidence interval (CI) 63.9 % to 98.1 %), whereas when only the GLIM score was used for malnutrition evaluation, sensitivity was 98.2 % (95 % CI, 92.8 % to 99.7 %). In addition, the PG-SGA score and the GLIM score had significant correlations., Conclusion: GLIM performed better than PG-SGA in the correlation analysis of nutritional indicators. GLIM is more suitable for patients with hepatobiliary and pancreatic malignancies than PG-SGA.

Polysaccharides and flavonoids have excellent antioxidant properties and tyrosinase inhibitory effects. In this paper, the antioxidant capacity of Inonotus sanghuang extract and its inhibition kinetics on mushroom tyrosinase were investigated to determine the preparation process of Inonotus sanghuang primary whitening gel. By conducting experimental studies on the effects of water extract and alcohol extract of Inonotus sanghuang on antioxidant capacity and tyrosinase activity, their inhibitory ability and types of inhibitory effects were determined. The single factor experiment was used to determine the preparation process of Sanghuang primary whitening gel. This study has proven that the extract of Inonotus sanghuang possesses antioxidant and tyrosinase inhibitory capabilities. It also identified the preparation process for the primary whitening gel of Inonotus sanghuang , thereby providing a theoretical and experimental basis for the development of whitening products utilising Inonotus sanghuang .

Rheumatoid arthritis (RA) is a complex autoimmune inflammatory rheumatic disease characterized by an imbalance between immunological reactivity and immune tolerance. Regulatory T cells (Tregs), which play a crucial role in controlling ongoing autoimmunity and maintaining peripheral tolerance, have shown great potential for the treatment of autoimmune inflammatory rheumatic diseases such as RA. This review aims to provide an updated summary of the latest insights into Treg-targeting techniques in RA. We focus on current therapeutic strategies for targeting Tregs based on discussing their subsets, surface markers, suppressive function, and signaling pathways in RA., 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 Masson SAS.. All rights reserved.)

Superradiant phase transitions play a fundamental role in understanding the mechanism of collective light-matter interaction at the quantum level. Here we investigate multiple superradiant phases and phase transitions with different symmetry-breaking patterns in a two-mode V-type Dicke model. Interestingly, we show that there exists a quadruple point where one normal phase, one global symmetry-breaking superradiant phase, and two local symmetry-breaking superradiant phases meet. Such a global phase results from the phase competition between two local superradiant phases and cannot occur in the standard Λ- and Ξ -type three-level configurations in quantum optics. Moreover, we exhibit a sequential first-order quantum phase transition from one local to the global again to the other local superradiant phase. Our study opens up a perspective of exploring multilevel quantum critical phenomena with global symmetry breaking.

Diode effects are of great interest for both fundamental physics and modern technologies. Electrical diode effects (nonreciprocal transport) have been observed in Weyl systems. Optical diode effects arising from the Weyl fermions have been theoretically considered but not probed experimentally. Here, we report the observation of a nonlinear optical diode effect (NODE) in the magnetic Weyl semimetal CeAlSi, where the magnetization introduces a pronounced directionality in the nonlinear optical second-harmonic generation (SHG). We demonstrate a six-fold change of the measured SHG intensity between opposite propagation directions over a bandwidth exceeding 250 meV. Supported by density-functional theory, we establish the linearly dispersive bands emerging from Weyl nodes as the origin of this broadband effect. We further demonstrate current-induced magnetization switching and thus electrical control of the NODE. Our results advance ongoing research to identify novel nonlinear optical/transport phenomena in magnetic topological materials and further opens new pathways for the unidirectional manipulation of light., (© 2024. The Author(s).)

Growing evidence has found the health protective effects of greenness exposure on tuberculosis (TB) and the impact of ambient air pollutants on TB drug-resistance. However, it remains unclear whether residential greenness is also beneficial to reduce TB drug-resistance, and whether air pollution modify the greenness-TB resistance relationship. We enrolled 5006 newly-diagnosed TB patients from Shandong, China, during 2014 to 2021. Normalized Difference Vegetation Index (NDVI) in 250 m and 500 m buffer around individuals' residential zone was used to assess greenness exposure. All patients were divided by quartiles of NDVI 250-m and NDVI 500-m (from low to high: Q1, Q2, Q3, Q4) respectively. Six logistic regression models (NDVI, NDVI + PM 2.5 /PM 10 /SO 2 /NO 2 /O 3 ) were used to estimate the association of NDVI and TB drug-resistance when adjusting different air pollutants or not. All models were adjusted for age, gender, body mass index, complications, smoking, drinking, population density, nighttime light index, road density. Compared with participants in NDVI 250-m Q1 and NDVI 500-m Q1, other groups had lower rates of MDR-TB, PDR-TB, RFP-resistance, SM-resistance, RFP + SM resistance, INH + RFP + EMB + SM resistance. NDVI 500-m reduced the risk of multidrug resistant tuberculosis (MDR-TB) and the adjusted odds ratio (aOR, 95% confidence interval, CI) compared with NDVI 500-m Q1 were 0.736 (0.547-0.991) in NDVI + PM 10 model, 0.733 (0.544-0.986) in NDVI + PM 2.5 model, 0.735(0.546-0.99) in NDVI + SO 2 model, 0.736 (0.546-0.991) in NDVI + NO2 model, respectively, P < 0.05. NDVI 500-m contributed to a decreased risk of streptomycin (SM)-resistance. The aOR of rifampicin (RFP) + SM resistance were 0.132 (NDVI 250-m , Q4 vs Q1, 95% CI: 0.03-0.578), 0.199 (NDVI 500-m , Q3 vs. Q1, 95% CI: 0.057-0.688) and 0.264 (NDVI 500-m , Q4 vs. Q1, 95% CI: 0.087-0.799). The adjusted ORs (Q2 vs. Q1, 95% CI) of isoniazid (INH) + RFP + ethambutol (EMB) + SM resistance in 500 m buffer were 0.276 (0.119-0.639) in NDVI model, 0.279 (0.11-0.705) in NDVI + PM 10 model, 0.281 (0.111-0.713) in NDVI + PM 2.5 model, 0.279 (0.11-0.709) in NDVI + SO2 model, 0.296 (0.117-0.754) in NDVI + NO 2 model, 0.294 (0.116-0.748) in NDVI + O 3 model, respectively. The study showed, for the first time, that residential greenness exposure in 500 m buffer is beneficial for reducing newly-diagnosed DR-TB (including PDR-RB, MDR-TB, MR-TB), and ambient air pollutants may partially mediate this association., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We present the measurements of all-particle energy spectrum and mean logarithmic mass of cosmic rays in the energy range of 0.3-30 PeV using data collected from LHAASO-KM2A between September 2021 and December 2022, which is based on a nearly composition-independent energy reconstruction method, achieving unprecedented accuracy. Our analysis reveals the position of the knee at 3.67±0.05±0.15  PeV. Below the knee, the spectral index is found to be -2.7413±0.0004±0.0050, while above the knee, it is -3.128±0.005±0.027, with the sharpness of the transition measured with a statistical error of 2%. The mean logarithmic mass of cosmic rays is almost heavier than helium in the whole measured energy range. It decreases from 1.7 at 0.3 PeV to 1.3 at 3 PeV, representing a 24% decline following a power law with an index of -0.1200±0.0003±0.0341. This is equivalent to an increase in abundance of light components. Above the knee, the mean logarithmic mass exhibits a power law trend towards heavier components, which is reversal to the behavior observed in the all-particle energy spectrum. Additionally, the knee position and the change in power-law index are approximately the same. These findings suggest that the knee observed in the all-particle spectrum corresponds to the knee of the light component, rather than the medium-heavy components.

Introduction: Systematic evaluation of long-term outcomes in survivors of H1N1 is still lacking. This study aimed to characterize long-term outcomes of severe H1N1-induced pneumonia and acute respiratory distress syndrome (ARDS)., Method: This was a single-center, prospective, cohort study. Survivors were followed up for four times after discharge from intensive care unit (ICU) by lung high-resolution computed tomography (HRCT), pulmonary function assessment, 6-minute walk test (6MWT), and SF-36 instrument., Result: A total of 60 survivors of H1N1-induced pneumonia and ARDS were followed up for four times. The carbon monoxide at single breath (D LCO ) of predicted values and the 6MWT results didn't continue improving after 3 months. Health-related quality of life didn't change during the 12 months after ICU discharge. Reticulation or interlobular septal thickening on HRCT did not begin to improve significantly until the 12-month follow-up. The D LCO of predicted values showed negative correlation with the severity degree of primary disease and reticulation or interlobular septal thickening, and a positive correlation with physical functioning. The D LCO of predicted values and reticulation or interlobular septal thickening both correlated with the highest tidal volume during mechanical ventilation. Levels of fibrogenic cytokines had a positive correlation with reticulation or interlobular septal thickening., Conclusion: The improvements in pulmonary function and exercise capacity, imaging, and health-related quality of life had different time phase and impact on each other during 12 months of follow-up. Long-term outcomes of pulmonary fibrosis might be related to the lung injury and excessive lung fibroproliferation at the early stage during ICU admission., 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 Tang, Xu, Wan, Zhao, Wang, Li, Li, Wang, Li, Gu, Zhang, Yang, Tong and Sun.)

Purpose: To assess the value of the driving pressure variation rate (ΔP%) in predicting the outcome of weaning from invasive mechanical ventilation in patients with acute respiratory distress syndrome., Methods: In this case-control study, a total of 35 patients with moderate-severe acute respiratory distress syndrome were admitted to the intensive care unit between January 2022 and December 2022 and received invasive mechanical ventilation for at least 48 h were enrolled. Patients were divided into successful weaning group and failed weaning group depending on whether they could be removed from ventilator support within 14 days. Outcome measures including driving pressure, PaO 2 :FiO 2 , and positive end-expiratory pressure, etc. were assessed every 24 h from day 0 to day 14 until successful weaning was achieved. The measurement data of non-normal distribution were presented as median (Q 1 , Q 3 ), and the differences between groups were compared by Wilcoxon rank sum test. And categorical data use the Chi-square test or Fisher's exact test to compare. The predictive value of ΔP% in predicting the outcome of weaning from the ventilator was analyzed using receiver operating characteristic curves., Results: Of the total 35 patients included in the study, 17 were successful vs. 18 failed in weaning from a ventilator after 14 days of mechanical ventilation. The cut-off values of the median ΔP% measured by Operator 1 vs. Operator 2 in the first 4 days were ≥ 4.17% and 4.55%, respectively (p < 0.001), with the area under curve of 0.804 (sensitivity of 88.2%, specificity of 64.7%) and 0.770 (sensitivity of 88.2%, specificity of 64.7%), respectively. There was a significant difference in mechanical ventilation duration between the successful weaning group and the failure weaning group (8 (6, 13) vs. 12 (7.5, 17.3), p = 0.043). The incidence of ventilator-associated pneumonia in the successful weaning group was significantly lower than in the failed weaning group (0.2‰ vs. 2.3‰, p = 0.001). There was a significant difference noted between these 2 groups in the 28-day mortality (11.8% vs. 66.7%, p = 0.003)., Conclusion: The median ΔP% in the first 4 days of mechanical ventilation showed good predictive performance in predicting the outcome of weaning from mechanical ventilation within 14 days. Further study is needed to confirm this finding., (Copyright © 2024 Chinese Medical Association. Production and hosting by Elsevier B.V. All rights reserved.)

The organizational citizenship behavior (OCB) of teachers is crucial for effective school functioning, and accessing valuable resources from principals greatly influences this behavior. Grounded in the conservation of resources (COR) theory, this study explored how a principal's emotional intelligence (EI) and teachers' organizational trust (OT) impact teachers' OCB. A survey was conducted on 521 elementary teachers in Taiwan using established scales to measure the constructs. Perceived principal's EI was assessed across self-awareness, self-management, social awareness, and relationship management dimensions. Similarly, teachers' OCB was examined through interpersonal citizenship performance, organizational citizenship performance, and job/task conscientiousness dimensions. Teachers' OT was explored in terms of personal trust in the individual, trust in the principal, and trust in the school. The mediation effect of OT in the relationship between a principal's EI and teachers' OCB was analyzed using Hayes' PROCESS macro for SPSS. The results yielded valuable evidence supporting the mediating model that teachers' OCB, influenced by the principal's EI, can be seen as secondary gains driven by higher levels of OT cultivated by emotionally intelligent principals. This study emphasizes the pivotal role of a principal's EI in fostering teachers' OT and OCB, underscoring the significance of EI in educational leadership. Investing in the EI development of school principals can nurture a positive school culture, enabling teachers to fully realize their potential and contribute to the overall well-being of the school community. However, the research results face limitations in generalizability due to the restricted sample size exclusive to Taiwan and the reliance on self-report measures in the study., Competing Interests: Declaration of competing interest The authors have no competing interests or other interests that might be perceived to influence the results and/or discussion reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: This study aimed to describe the lineage-specific transmissibility and epidemiological migration of Mycobacterium tuberculosis in China., Methods: We curated a large set of whole-genome sequences from 3204 M. tuberculosis isolates, including thousands of newly sequenced genomes, and applied a series of metrics to compare the transmissibility of M. tuberculosis strains between lineages and sublineages. The countrywide transmission patterns of major lineages were explored., Results: We found that lineage 2 (L2) was the most prevalent lineage in China (85.7%), with the major sublineage 2.2.1 (80.9%), followed by lineage 4 (L4) (13.8%), which comprises major sublineages 4.2 (1.5%), 4.4 (6.2%) and 4.5 (5.8%). We showed evidence for frequent cross-regional spread and large cluster formation of L2.2.1 strains, whereas L4 strains were relatively geographically restricted in China. Next, we applied a series of genomic indices to evaluate M. tuberculosis strain transmissibility and uncovered higher transmissibility of L2.2.1 compared with the L2.2.2 and L4 sublineages. Phylogeographic analysis showed that southern, eastern, and northern China were highly connected regions for countrywide L2.2.1 strain spread., Conclusions: The present study provides insights into the different transmission and migration patterns of the major M. tuberculosis lineages in China and highlights that transmissible L2.2.1 is a threat to tuberculosis control., Competing Interests: Declaration of competing interest The authors have no competing financial interests to declare., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Microdissection testicular sperm extraction is an effective method to retrieve sperm from non-obstructive azoospermia patients. However, its successful rate is less than 50%., Objectives: To identify the predictive value of circular RNAs in serum for sperm retrieval rate in non-obstructive azoospermia patients., Materials and Methods: 180 non-obstructive azoospermia patients were recruited in this study, including 84 individuals with successful sperm retrieval and 96 individuals with failed sperm retrieval. Our study contained two phases. First, 20 patients, selected from the 180 patients, were included in screening cohort. In this cohort, the top 20 circular RNAs from our previous testicular circRNA profiles were verified between successful and failed sperm retrieval groups using real-time polymerase chain reaction. Six circular RNAs with the most significantly different expressions were selected for further verification. Second, the 180 patients were included as discovery cohort to verify the six circular RNAs. Circular RNAs were extracted from serum in each participant. Logistic regression analysis was further performed to identify the predictive value and the area under the curve analysis was used to evaluate diagnostic efficiency, sensitivity, and specificity., Results: Six circular RNAs including hsa&#95;circ&#95;0058058, hsa&#95;circ&#95;0008045, hsa&#95;circ&#95;0084789, hsa&#95;circ&#95;0000550, hsa&#95;circ&#95;0007422, and hsa&#95;circ&#95;0004099 showed aberrant expressions between the successful and failed sperm retrieval group. In addition, both single-circular RNA panels and multi-circular RNA panels were finally verified to be significant in predicting sperm retrieval rate. Notably, multi-circular RNAs panels demonstrated better predictive abilities compared with single-circRNA panels, and the combined panel of six-circular RNAs (risk score = 1.094×hsa&#95;circ&#95;0058058+0.697×hsa&#95;circ&#95;0008045+0.718×hsa&#95;circ&#95;0084789-0.591×hsa&#95;circ&#95;0000550-0.435×hsa&#95;circ&#95;0007422-1.017×hsa&#95;circ&#95;0004099-1.561) exhibited the best predictive ability in the present study with an AUC of 0.977, a sensitivity of 91.7% and a specificity of 86.5%. A higher risk score indicated a higher risk of failure in sperm retrieval., Discussion and Conclusion: Our study was the first to report that testis-derived circular RNAs in serum have the ability to predict sperm retrieval rate in non-obstructive azoospermia patients, whether it is a single-circular RNA or a combination of multi-circular RNAs., (© 2024 American Society of Andrology and European Academy of Andrology.)

Introduction: Parkinson's disease (PD) remains one kind of a complex, progressive neurodegenerative disease. Levodopa and dopamine agonists as widely utilized PD therapeutics have not shown significant positive long-term outcomes. Emerging evidences indicate that electroacupuncture (EA) have potential effects on the therapy of nervous system disorders, particularly PD, but its specific underlying mechanism(s) remains poorly understood, leading to the great challenge of clinical application and management. Previous study has shown that acupuncture ameliorates PD motor symptoms and dopaminergic neuron damage by modulating intestinal dysbiosis, but its intermediate pathway has not been sufficiently investigated., Methods: A rat model of PD was induced using rotenone. The therapeutic effect of EA on PD was assessed using the pole and rotarod tests and immunohistostaining for tyrosine hydroxylase (TH) in the substantia nigra (SN) of brain. The role of gut microbiota was explored using 16S rRNA gene sequencing and metabonomic analysis. PICRUSt2 analysis, lipidomic analysis, LPS and inflammatory factor assays were used for subsequent exploration and validation. Correlation analysis was used to identify the key bacteria that EA regulates lipid metabolism to improve PD., Results: The present study firstly reappeared the effects of EA on protecting motor function and dopaminergic neurons and modulation of gut microbial dysbiosis in rotenone-induced PD rat model. EA improved motor dysfunction (via the pole and rotarod tests) and protected TH+ neurons in PD rats. EA increased the abundance of beneficial bacteria such as Lactobacillus, Dubosiella and Bifidobacterium and decreased the abundance of Escherichia-Shigella and Morganella belonging to Pseudomonadota, suggesting that the modulation of gut microbiota by EA improving the symptoms of PD motility via alleviating LPS-induced inflammatory response and oxidative stress, which was also validated by various aspects such as microbial gene functional analysis, fecal metabolomics analysis, LPS and inflammatory factor assays and SNpc lipidomics analysis. Moreover, correlation analyses also verified strong correlations of Escherichia-Shigella and Morganella with motor symptoms and SNpc lipid peroxidation, explicating targets and intermediate pathways through which EA improve PD exercise symptom., Conclusion: Our results indicate that the improvement of motor function in PD model by EA may be mediated in part by restoring the gut microbiota, which intermediate processes involve circulating endotoxins and inflammatory mediators, SNpc oxidative stress and lipid peroxidation. The gut-microbiome - brain axis may be a potential mechanism of EA treatment for the PD., 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 Hu, Song, Zhang, Ruan, Li, Yu and Huang.)

Aim: To investigate the effects of Sonic hedgehog ( Shh ) gene-modified bone marrow mesenchymal stem cells (MSCs) on graft-induced retinal gliosis and retinal ganglion cells (RGCs) survival in diabetic mice., Methods: Bone marrow-derived MSCs were genetically modified with the Shh gene to generate a stably transfected cell line of Shh -modified MSCs (MSC-Shh). Intravitreal injections of MSC-Shh and green fluorescent protein-modified MSCs (MSC-Gfp; control) were administered in diabetic mice. After 4wk, the effects of MSC-Shh on retinal gliosis were evaluated using fundus photography, and markers of gliosis were examined by immunofluorescence and Western blotting. The neurotrophic factors expression and RGCs survival in the host retina were evaluated using Western blotting and immunofluorescence. The mechanisms underlying the effects of MSC-Shh was investigated., Results: A significant reduction of proliferative vitreoretinopathy (PVR) was observed after intravitreal injection of MSC-Shh compared to MSC-Gfp. Significant downregulation of glial fibrillary acidic protein (GFAP) was demonstrated in the host retina after MSC-Shh administration compared to MSC-Gfp. The extracellular signal-regulated kinase 1/2 (ERK1/2), protein kinase B (AKT) and phosphatidylin-ositol-3-kinase (PI3K) pathways were significantly downregulated after MSC-Shh administration compared to MSC-Gfp. Brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) levels were significantly increased in the host retina, and RGCs loss was significantly prevented after MSC-Shh administration., Conclusion: MSC-Shh administration reduces graft-induced reactive gliosis following intravitreal injection in diabetic mice. The ERK1/2, AKT and PI3K pathways are involved in this process. MSC-Shh also increases the levels of neurotrophic factors in the host retina and promoted RGCs survival in diabetic mice., (International Journal of Ophthalmology Press.)

Acute respiratory distress syndrome (ARDS) is a collection of clinical syndromes characterized by a variety of heterogeneous causes. It includes diffuse lung diseases of various etiologies that ultimately lead to refractory hypoxia and severe acute respiratory failure. Despite advances in research and treatment of ARDS, its incidence and mortality continue to pose significant challenges in clinical practice. Since its inception in 1967, the definition of ARDS has undergone several revisions that have generated controversy and influenced the implementation of diagnostic and treatment strategies. At present, ARDS remains a formidable obstacle to both diagnosis and treatment. This article undertakes a comprehensive review of the evolution of ARDS definitions, examines the current diagnostic paradigm, and explores its far-reaching consequences. Our aim is to identify research directions, both in the realm of basic science and clinical practice, that are consistent with the nature of this complex disorder.

Introduction: Tuberculosis (TB) is an infectious disease caused by a bacterium called Mycobacterium tuberculosis ( Mtb ). Previous studies have primarily focused on the transmissibility of multidrug-resistant (MDR) or extensively drug-resistant (XDR) Mtb . However, variations in virulence across Mtb lineages may also account for differences in transmissibility. In Mtb , polyketide synthase (PKS) genes encode large multifunctional proteins which have been shown to be major mycobacterial virulence factors. Therefore, this study aimed to identify the role of PKS mutations in TB transmission and assess its risk and characteristics. Methods: Whole genome sequences (WGSs) data from 3,204 Mtb isolates was collected from 2011 to 2019 in China. Whole genome single nucleotide polymorphism (SNP) profiles were used for phylogenetic tree analysis. Putative transmission clusters (≤10 SNPs) were identified. To identify the role of PKS mutations in TB transmission, we compared SNPs in the PKS gene region between "clustered isolates" and "non-clustered isolates" in different lineages. Results: Cluster-associated mutations in ppsA, pks12, and pks13 were identified among different lineage isolates. They were statistically significant among clustered strains, indicating that they may enhance the transmissibility of Mtb . Conclusion: Overall, this study provides new insights into the function of PKS and its localization in M. tuberculosis . The study found that ppsA, pks12, and pks13 may contribute to disease progression and higher transmission of certain strains. We also discussed the prospective use of mutant ppsA , pks12 , and pks13 genes as drug targets., 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 Wang, Hu, Li, Kong, Li, Sun, Wang, Li, Zhang, Han, Zhu, An, Liu, Liu and Li.)

Since reef ecosystems can offer intricate habitats for various marine organisms, calcified reefs may contain valuable long-term environmental data. This study investigated stable isotopic composition of marine organisms from the Taoyuan and Linshanbi crustose coralline algae (CCA) reef ecosystems to understand sewage pollution. CCA samples from Taoyuan (Palaeo Xin A: ∼1000 years old and Palaeo G: ∼7000 years old) and Linshanbi (Palaeo L: ∼7000 years old and modern CCA) had significantly lower δ 15 N values (2.5-5.6 ‰) compared to modern CCA from Taoyuan (10.2 ± 1.2 ‰). Intertidal organisms from the Taoyuan CCA reef also showed higher δ 15 N values than those from Linshanbi CCA reef, indicating anthropogenic stress in both ecosystems. Long-term pollution monitoring and effective strategies to mitigate sewage pollution are recommended for these CCA reef ecosystems., 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 Ltd. All rights reserved.)