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Yao-Jie Pan,1 Jian Wan,2 Chun-Bin Wang1 1Department of Oncology, The Affiliated Yancheng Hospital of Medicine School of Southeast University, The Third People’s Hospital of Yancheng, Yancheng 224001, People’s Republic of China; 2Department of General Surgery, Center for Difficult and Complicated Abdominal Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200092, People’s Republic of ChinaCorrespondence: Chun-Bin WangDepartment of Oncology, The Affiliated Yancheng Hospital of Medicine School of Southeast University, The Third People’s Hospital of Yancheng, 75 Juchang Road, Yancheng, Jiangsu 224001, People’s Republic of ChinaTel +86-515-81606113Email yclvwenping@163.comAbstract: MicroRNAs (miRNAs) are small non-coding and highly conserved RNAs that act in biological processes including cell proliferation, invasion, apoptosis, metabolism, signal transduction, and tumorigenesis. The previously identified miRNA-326 (miR-326) has been reported to participate in cellular apoptosis, tumor growth, cell invasion, embryonic development, immunomodulation, chemotherapy resistance, and oncogenesis. This review presents a detailed overview of what is known about the effects of miR-326 on cell invasion, metastasis, drug resistance, proliferation, apoptosis, and its involvement in signaling pathways.Keywords: MicroRNA, miR-326, tumor suppressor, cancer, metastasis, oncogene

JY Ren,* DM Lin,* CB Wang, YL Yang, ZQ Wang, BQ Cui, J Ma Department of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University-Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: J MaDepartment of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University-Beijing Institute of Heart Lung and Blood Vessel Diseases, No.2 Anzhen Road, Chaoyang District, Beijing 100029, People’s Republic of ChinaTel +8613370103571Email majuntongxun@sohu.comBackground/Aims: To investigate the postconditioning protective effect of penehyclidine hydrochloride (PHC) against anoxia/reoxygenation (A/R) injury in H9c2 cells along with the involved mechanism and timing effect.Methods: We divided H9c2 cells into 7 groups: control group, A/R group and PHC+A/R groups at 0 min, 5 mins, 10 mins, 20 mins, 30 mins, respectively (treated with 0.1 μm/L PHC at 0 min, 5 mins, 10 mins, 20 mins, 30 mins after the reoxygenation procedure began). Cell apoptosis, oxidative stress, intracellular Ca2+ concentration, mitochondrial membrane potential and mitochondrial permeability transition pore (MPTP) opening were explored. Bcl-2, Bax, Cyt C, caspase-3 and caspase-9 levels were measured.Results: A/R significantly increased both cell injury and cell apoptosis. PHC showed postconditioning protective effect by attenuating superoxide production, decreasing Ca2+ overload, restraining MPTP activities, restoring mitochondrial membrane potential, regulating cell apoptosis proteins and modulation of mitochondrial pathway. Earlier administration of PHC offered greater postconditioning protective effect.Conclusion: H9c2 cells were protected by PHC from A/R injury regardless of timing of PHC administration (0 min, 5 mins, 10 mins, 20 mins, 30 mins). However, earlier administration of PHC resulted in better PHC postconditioning protection.Keywords: penehyclidine hydrochloride, PHC, anoxia/reoxygenation injury, A/R injury, cell apoptosis, oxidative stress, mitochondrial pathway

Yu Xia, Min Guo, Tiantian Xu, Yinghua Li, Changbing Wang, Zhengfang Lin, Mingqi Zhao, Bing Zhu Virus Laboratory, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China Background: Small interfering RNA (siRNA) as a new therapeutic modality holds promise for cancer treatment. However, the traditional viral carriers are prone to immunogenicity and risk of insertional mutagenesis.Methods: In order to provide a tumor-targeted delivery carrier of siRNA in cancer therapy, the hyaluronic acid (HA)-selenium (Se)-polyethylenimine (PEI) nanoparticle (NP) was fabricated by decorating SeNP with HA as a tumor-targeting moiety and by linking the polycationic polymers polyethylenimine PEI onto the surface of SeNP. The siRNA was loaded to the surface of SeNP HA-Se-PEI via the electrostatic interaction between siRNA and PEI to prepare the functionalized SeNP HA-Se-PEI@siRNA. Results: The HA-Se-PEI@siRNA was internalized into the HepG2 cell mainly in a clathrin-mediated endocytosis manner. Owing to the active tumor-targeted effect mediated by HA, HA-Se-PEI@siRNA achieved the obvious higher transfection efficiency, greater gene silencing ability, and stronger cytotoxicity in the HepG2 cell compared with the passive tumor-targeted NP Se-PEI@siRNA. The knockdown of hairy and enhancer of split 5 by HA-Se-PEI@siRNA induced the HepG2 cell cycle arrest at the G0/G1 phase and apoptosis. Furthermore, the treatment with HA-Se-PEI@siRNA resulted in greater antitumor efficacy compared with the Se-PEI@siRNA in vitro and in vivo. In addition, the HA-Se-PEI@siRNA was almost no toxic to the key organs of mice. Conclusion: These findings provided an alternative therapeutic route for targeted cancer treatments. Keywords: hepatocellular carcinoma, functionalized nanoparticle, siRNA delivery, gene therapy, tumor targeting

Ting-ting Liu,1–3 Li-Qiu Mu,1–3 Wei Dai,1–3 Chuan-bang Wang,1–3 Xin-Yi Liu,1–3 Da-Xiong Xiang1–3 1Department of Pharmacy, The Second Xiangya Hospital, 2Institute of Clinical Pharmacy, Central South University, 3Key Laboratory for New Technology of Chinese Medicine Preparations of Hunan Province, Changsha, People’s Republic of China Abstract: The purpose of this study was to prepare Brucea javanica oil cationic nanoemulsions (BJO-CN) with BJO as drug as well as oil phase and chitosan as cationic inducer, to explore the practical suitability of using cationic nanoemulsions for oral delivery of mixed oil, and to test its bioavailability and antitumor effect. BJO-CN was prepared by chitosan solution stirring method and then characterized physicochemically. The obtained BJO-CN had a spherical morphology with a positive zeta potential of 18.9 mV and an average particle size of 42.36 nm, showing high colloidal stability. The drug loading of BJO-CN was 91.83 mg·mL-1, determined by high-performance liquid chromatography with precolumn derivatization. Pharmacokinetic studies revealed that, compared with BJO emulsion (BJO-E) (the dosage of BJO-CN and BJO-E was equal to 505 mg·kg-1, calculated by oleic acid), BJO-CN exhibited a significant increase in the area under the plasma drug concentration–time curve over the period of 24 hours and relative bioavailability was 1.6-fold. Furthermore, the antitumor effect of BJO-CN in the orthotopic mouse model of lung cancer was evaluated by recording the median survival time and the weight of lung tissue with tumor, hematoxylin and eosin staining, and immunohistochemical technique. Results of anticancer experiments illustrated that, even though the administrated dosage in the BJO-CN group was half of that in the BJO-E group, BJO-CN exhibited similar antitumor effect to BJO-E. Moreover, BJO-CN had good synergistic effect in combination therapy with vinorelbine. These results suggested that cationic nanoemulsions are an effective and promising delivery system to enhance the oral bioavailability and anticancer effect of BJO. Keywords: oleic acid, chitosan, combined chemotherapy, orthotopic mouse model of lung cancer, pharmacokinetics

Purpose: To determine the cellular and molecular mechanism of cytotoxicity induced by Haishengsu (HSS), nature extract from Tegillarca granosa, toward human ovarian cancer cell lines SKOV-3 and OVCAR-3.Methods: The cytotoxic effects of HSS on two ovarian cancer cell lines were tested by XTT assay. Cell apoptosis and cell cycle arrest induced by HSS were demonstrated by DNA ladder assay and flow cytometric analysis, respectively. RT-PCR or flow cytometric analysis was used to investigate the expression of bcl-2, caspase-3, p53, beta-catenin, E-cadherin, CD24, and CD44.Results: Continuous exposure to HSS for 48 h produced cytotoxic effects on both cell lines in a concentration dependent manner, which was accompanied by apoptosis and cell cycle arrest. Apoptosis associated gene bcl-2 and caspase-3, tumor metastasis associated gene ?-catenin, but not E-cadherin, and CD24, but not CD44, were involved in the effect of growth inhibition induced by HSS. Although p53 mediated apoptosis induced by HSS in OVCAR-3 cells, it was not required in SKOV-3 cells.Conclusion: HSS has a potential cytotoxic effect on human ovarian cancer cells, which was mediated by multiple signal molecules including bcl-2, caspase-3, beta-catenin, and CD24. These findings will provide a theoretical basis for HSS's potential clinical application as a novel marine anti-cancer agent. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the pharmacokinetics of L-carnitine (LC) and its analogues, acetyl-L-carnitine (ALC) and propionyl-L-carnitine (PLC) in healthy volunteers after single L-carnitine administration.Methods: Liquid L-carnitine (2.0 g) was administered orally as a single dose in 12 healthy subjects. Plasma and urine concentrations of L-carnitine, ALC and PLC were detected by HPLC.Results: The maximum plasma concentration (Cmax) and area under the curve (AUC 0-infinity) of L-carnitine was 84.7+/-25.2 micromol x L(-1) x h and 2676.4+/-708.3 micromol x L(-1) x h, respectively. The elimination half-life of L-carnitine and the time required to reach the Cmax (Tmax) was 60.3+/-15.0 and 3.4+/-0.46 h, respectively. The Cmax of ALC (12.9+/-5.5 micromol x L(-1)) and PLC (5.08+/-3.08 micromol x L(-1)) was lower than L-carnitine (P < 0.01), so as the AUC 0-infinity (166.2+/-77.4 and 155.6+/-264.2 micromol x L(-1) x h, respectively, P < 0.01). The half-life of ALC (35.9+/-28.9h) and PLC (25.7+/-30.3 h) was also shorter than L-carnitine (P < 0.01). The 24h accumulated urinary excretion of L-carnitine, ALC and PLC were 613.5+/-161.7, 368.3+/-134.8 and 61.3+/-37.8 micromol, respectively.Conclusion: L-carnitine has a greater maximum plasma concentration than ALC and PLC. L-carnitine also has a longer half-life than ALC and PLC. These data may have important implications in the designing of dosing regimens for L-carnitine or its analogues, such as ALC or PLC. [ABSTRACT FROM AUTHOR]

Background: From August to September 2024, we led a team of Guangzhou No.5 Binjiang Junior High School students to study the community structure of leaf litter beetles in Guangzhou, Guangdong Province, southern China, to prepare for the Youth Innovation Competition hosted by the Guangzhou Education Bureau. In the study, 479 specimens were collected in total, identified as 73 species in 14 families. Amongst all the specimens, some are considered new species, one of which is described here.The genus Trachyphloeosoma Wollaston, 1869 (Coleoptera, Curculionidae, Entiminae, Trachyphloeini) includes six known species occurring in China and the genus is recorded in Guangdong Province for the first time., New Information: A new weevil, Trachyphloeosomarutiani sp. nov. (Coleoptera, Curculionidae, Entiminae), is described from Guangzhou City, Guangdong Province, China. Important morphological characters of the new species are illustrated by colour plates., (Jiang Zhu, Cheng-Bin Wang, Ye Zhen.)

Background: Biopsy is the gold standard method for diagnosing liver fibrosis. FibroScan is a non-invasive method of diagnosing liver fibrosis, but it still faces some limitations. This study aimed to establish a nomogram model and identify patients at high risk of advanced liver fibrosis associated with hepatitis B infection., Methods: Data were collected from 375 patients with hepatitis B who underwent liver biopsy. Patients were divided randomly into the training (n = 263) and validation sets (n = 112). Their demographic and clinical characteristics were analyzed using the least absolute shrinkage and selection operator regression (LASSO). A nomogram model was established to predict the fibrosis stage, and its performance was assessed using the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA) and was compared with other recognized models., Results: In total, 209 patients with non-advanced fibrosis (S0-1) and 166 patients with advanced fibrosis (S ≥ 2) were included. Hyaluronic acid (HA), laminin, total cholesterol (TC), platelet, and age were entered into the nomogram model based on the LASSO analysis. The nomogram model for predicting advanced fibrosis exhibited a relatively high AUC in the training set. Compared with FIB4 and APRI, the nomogram model showed a better agreement between the actual status and predicted status based on the calibration curve. The nomogram model showed an AUC similar to FibroScan in the validation cohort, and showed high clinical net benefits in the training and validation sets., Conclusion: Our nomogram model can help identify patients with hepatitis B and advanced liver fibrosis., 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. Published by Elsevier B.V.)

Background: This meta-analysis aimed to investigate the effect of statins on the prognosis of patients with intracerebral hemorrhage (ICH)., Methods: We conducted a systematic search using the keywords "statin" and "intracerebral hemorrhage" across four electronic databases (PubMed, Cochrane Library, Web of Science, and Embase) from their inception to October 31, 2023, to identify studies comparing the effects of statins on the prognosis of patients with ICH. The primary outcome was total mortality after ICH. This meta-analysis was registered online (PROSPERO ID: CRD42023493063)., Results: Our initial search identified 5,543 studies. After applying inclusion criteria, 30 studies with a total of 42,298 patients were included in the final analysis. Our meta-analysis showed that statins significantly reduced overall mortality in patients with ICH (OR: 0.61; 95% CI: 0.51-0.73; I 2  = 87%; p  < 0.01). Subgroup analyses further demonstrated lower mortality in ICH patients treated with statins compared to those not treated, including in the propensity score matching (PSM) group (OR: 0.59; 95% CI: 0.48-0.74; I 2  = 90%; p  < 0.01), the prospective cohort study (PCS) group (OR: 0.56; 95% CI: 0.40-0.77; I 2  = 89%, p  < 0.01), and the retrospective cohort study (RCS) group (OR: 0.64; 95% CI: 0.51-0.81; I 2  = 87%, p  < 0.01)., Conclusion: Our meta-analysis of 30 studies suggests that statin use may be associated with improved mortality and functional outcomes in patients with intracerebral hemorrhage (ICH)., Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, CRD42023493063., 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 © 2025 Li, Xu, Wang, Yang, Shi, Wang, Xu and Jiang.)

A novel analytical method was designed and developed that exhibited ultraviolet-visible (UV-Vis), fluorescence (FL), and resonance Rayleigh scattering (RRS) signals for straightforward and comprehensive determination of monoamine oxidase B (MAO-B) using polyethylenimine-functionalized silver nanoparticles (PEI-Ag NPs). Through a facile one-step experiment, and NaOH assisted, in an aqueous solution of 100 ℃ for 40 min PEI reacted with AgNO 3 to generate PEI-Ag NPs with a yellow color and weak blue fluorescence. Interestingly, phenylacetaldehyde (PAA), a specific product of MAO-B, causes significant enhancement of the three optical signals of UV-Vis, FL, and RRS. A triple-signal readout sensing system was designed and constructed for MAO-B concentration assay. The limit of detection (LOD) was 0.42 (UV-Vis), 3.49 (FL), and 1.97 (RRS) μg/mL. AND logic gate analysis was applied to enhance its accurate identification. Eventually, the feasibility of the method was assessed by measuring MAO-B amount in human serum samples with satisfying recoveries. The method provided a new concept for the clinical detection of MAO-B., Competing Interests: Declarations. Ethical approval: This study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of School of Basic Medicine, Lanzhou University (LZUjcyxy20240330). All participants provided the informed consent before the start of the experiment. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

A practical and efficient trans -diboration of propargyl alcohols was accomplished using sodium hydride (NaH) as a base in N , N -dimethylformamide at room temperature. The mild reaction conditions demonstrate general applicability, facilitating the successful conversion of both terminal and internal propargyl alcohols with diverse structures and functional groups into highly functionalized alkenediboronates [4-borylated 1,2-oxaborol-2(5 H )-oles]. The resulting products, which incorporate two boron groups, can be selectively activated and subjected to stepwise transformations, thereby providing an effective platform for synthesizing a wide range of structurally diverse trisubstituted alkenes.

This multicohort phase II trial (ALTER-G-001; NCT05262335) aimed to assess the efficacy of first-line anlotinib plus chemotherapy for gastrointestinal (GI) cancer patients with unresectable liver metastases. Eligible patients with colorectal cancer (Cohort A) or noncolorectal and nonesophageal GI cancer (Cohort C) received six cycles of anlotinib plus standard chemotherapeutic regimens followed by anlotinib plus metronomic capecitabine as a maintenance therapy. Liver metastasectomy can be performed when liver metastases are converted to resectable lesions. The primary outcome was the investigator-confirmed objective response rate (ORR) in the intention-to-treat population. Among the 47 patients in Cohort A, the ORR was 40.4% (95% CI 26.4-55.7), including 1 with a complete response (CR) and 18 who achieved a partial response (PR). The median progression-free survival (PFS) was 8.7 months (95% CI 7.3-NE), and the median overall survival (OS) was not reached. In Cohort C, 14 of 44 patients achieved a PR, with an ORR of 31.8% (95% CI 18.6-47.6). The PFS and OS were 5.8 months (95% CI 4.8-6.5) and 11.4 months (95% CI 5.8-19.3), respectively. The liver metastasectomy rate in patients with liver-limited disease was 22.7% (5/22) in Cohort A and 6.7% (2/30) in Cohort C. For pancreatic cancer patients, the ORR of the efficacy-evaluable population was 36.0% (9/25), and those with liver-limited metastasis had better survival. Moreover, no new safety concerns emerged. In conclusion, an anlotinib-based first-line regimen demonstrated promising antitumor activity among GI cancer patients with unresectable liver metastases and led to liver metastasectomy in selected patients., Competing Interests: Competing interests: The authors declare that they have no competing interests. Inclusion and Ethics: The trial was conducted in accordance with the Declaration of Helsinki, the Good Clinical Practice guidelines of the International Conference on Harmonization, and relevant laws and directives in China. The study protocols and all amendments were approved by the ethics committee of the Ruijin Hospital Ethics Committee, Shanghai Jiao Tong University School of Medicine (2021-223). All patients provided written informed consent before any trial-related activities. This trial is registered with CLINICALTRIALS.GOV (NCT05262335). The study protocols and all amendments were approved by the institutional review board or ethics committee of each participating center. Informed consent: All patients provided written informed consent before any trial-related activities., (© 2024. The Author(s).)

Extracellular matrix (ECM) scaffold membranes have exhibited promising potential to better the outcomes of wound healing by creating a regenerative microenvironment around. However, when compared to the application in younger individuals, the performance of the same scaffold membrane in promoting re-epithelialization and collagen deposition was observed dissatisfying in aged mice. To comprehensively explore the mechanisms underlying this age-related disparity, we conducted the integrated analysis, combing single-cell RNA sequencing (scRNA-Seq) with spatial transcriptomics, and elucidated six functionally and spatially distinctive macrophage groups and lymphocytes surrounding the ECM scaffolds. Through intergroup comparative analysis and cell-cell communication, we characterized the dysfunction of Spp1+ macrophages in aged mice impeded the activation of the type Ⅱ immune response, thus inhibiting the repair ability of epidermal cells and fibroblasts around the ECM scaffolds. These findings contribute to a deeper understanding of biomaterial applications in varied physiological contexts, thereby paving the way for the development of precision-based biomaterials tailored specifically for aged individuals in future therapeutic strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues. Methods: From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed. Results: This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI : 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI : 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI : 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI : 6.6-11.2 months), and their mOS was 15.5 months (95% CI : 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI : 3.4-5.1 months), and their mOS was 9.3 months (95% CI : 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR =1.47, 95% CI : 1.06-2.04), primary tumor site ( HR =0.64, 95% CI : 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR =2.66, 95% CI : 1.53-4.65), and whether to combine radiotherapy ( HR =0.65, 95% CI : 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR =0.68, 95% CI : 0.48-0.95), ECOG score ( HR =5.82, 95% CI : 3.14-10.82), and whether to combine radiotherapy ( HR =0.58, 95% CI : 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B , PTEN , FGF6 , and RBBP8 genes were significantly associated with an increased risk of death ( P ＜0.05). Conclusion: Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Background: The genus Apharinodes Raffray, 1890 (Coleoptera, Staphylinidae, Pselaphinae, Hybocephalini) includes four known species occurring in East and Southeast Asia., New Information: A new species, Apharinodesbaixiensis sp. nov. , is described from Heyuan City, Guangdong Province, China. Important morphological characters of the new species are illustrated by colour plates., (Jiang Zhu, Cheng-Bin Wang.)

Three new rhagophthalmids of the genus Diplocladon Gorham, 1883 are described from China, i.e. D. maai sp. nov. from Fujian, D. nezha sp. nov. from Yunnan, and D. wukong sp. nov. from Chongqing. Diplocladon atripenne Yiu, 2017 is redescribed and first recorded from Guangdong and Guangxi. Illustrations of the habituses and diagnostic characters of all four Chinese species are provided; a key to Chinese species of Diplocladon based on males is compiled; and a map is presented to exhibit their distributions.

An unexpected troglobitic staphylinid is described from a dolomite cave in western China as Domenelizeyui Wang & He, sp. nov. (Coleoptera, Staphylinidae, Paederinae). The habitus of both sexes and important diagnostic features are illustrated. Brief notes on the habitat, biology and taxonomic status of the new species are provided. This is the first discovery of a troglobitic representative of Paederinae from China, the first record of a troglobitic Domene species, and only the third cavernicolous species of Paederinae from eastern Asia., Competing Interests: The authors have declared that no competing interests exist., (Cheng-Bin Wang, Li He.)

The rapid variation of influenza challenges vaccines and treatments, which makes an urgent task to develop the high-efficiency and low-toxicity new anti-influenza virus drugs. Selenium is one of the essential trace elements for the human body that possesses a good antiviral activity. In this study, we assessed anti-influenza A virus (H1N1) activity of polyethylene glycol (PEG)-modified gray selenium nanoparticles (PEG-SeNPs) on Madin-Darby Canine Kidney (MDCK) cells in vitro. CCK-8 assay showed that PEG-SeNPs had a protective effect on H1N1-infected MDCK cells. Moreover, PEG-SeNPs significantly reduced the mRNA level of H1N1. TUNEL-DAPI test showed that DNA damage reached a high level but effectively prevented after PEG-SeNPs treatment. Meanwhile, JC-1, Annexin V-FITC and cell cycle assay demonstrated the apoptosis induced by H1N1 was reduced greatly when treated with PEG-SeNPs. Furthermore, the downregulation of p-ATM, p-ATR and P53 protein, along with the upregualation of AKT protein indicated that PEG-SeNPs could inhibit H1N1-induced cell apoptosis through reactive oxygen species (ROS)-mediated related signaling pathways. Finally, Cytokine detection demonstrated PEG-SeNPs inhibited the production of pro-inflammatory factors after infection, including IL-1β, IL-5, IL-6, and TNF-α. To sum up, PEG-SeNPs might become a new potential anti-H1N1 influenza virus drug due to its antiviral and anti-inflammatory activity., (© 2024. The Author(s).)

On 9 October 2022, the Large High Altitude Air Shower Observatory (LHAASO) reported the observation of the very early TeV afterglow of the brightest-of-all-time gamma-ray burst 221009A, recording the highest photon statistics in the TeV band ever obtained from a gamma-ray burst. We use this unique observation to place stringent constraints on the energy dependence of the speed of light in vacuum, a manifestation of Lorentz invariance violation (LIV) predicted by some quantum gravity (QG) theories. Our results show that the 95% confidence level lower limits on the QG energy scales are E&#95;{QG,1}>10 times the Planck energy E&#95;{Pl} for the linear LIV effect, and E&#95;{QG,2}>6×10^{-8}E&#95;{Pl} for the quadratic LIV effect. Our limits on the quadratic LIV case improve previous best bounds by factors of 5-7.

In this Letter we try to search for signals generated by ultraheavy dark matter at the Large High Altitude Air Shower Observatory (LHAASO) data. We look for possible γ rays by dark matter annihilation or decay from 16 dwarf spheroidal galaxies in the field of view of the LHAASO. Dwarf spheroidal galaxies are among the most promising targets for indirect detection of dark matter that have low fluxes of astrophysical γ-ray background while having large amount of dark matter. By analyzing more than 700 days of observational data at LHAASO, no significant dark matter signal from 1 TeV to 1 EeV is detected. Accordingly we derive the most stringent constraints on the ultraheavy dark matter annihilation cross section up to EeV. The constraints on the lifetime of dark matter in decay mode are also derived.

Objective: Alzheimer's disease (AD), a common degenerative disease of the central nervous system in the elderly, has become the third largest health killer after cardiovascular and cerebrovascular diseases and tumors. Based on the fact that Alzheimer's disease is a disease with multiple etiologies and complex pathology, a single target is bound to have a limited curative effect, and the synergy of multiple links and multiple targets is expected to achieve a better curative effect. The aim of this study is to investigate the brain targeting of a drug modified by chitosan, based on the new nanodrug delivery system for treating Alzheimer's disease developed by the research group., Materials and Methods: Chitosan with good biocompatibility, biosorption, and degradation products that can protect and promote the regeneration of nerve cells was selected to combine with galantamine, a natural representative cholinesterase inhibitor, to develop a new nano drug delivery system for nasal delivery of anti-Alzheimer's disease with a multi-target synergistic effect. Synchronous analysis was conducted on the blood and brain tissue drug concentrations after intravenous and nasal administration of the original drug solution and system solution. The brain targeting index (DTI) is used to evaluate the brain targeting effect of the nano-drug delivery system after intranasal administration., Results: The blood concentration of galantamine original drug solution and galantamine system solution after intravenous injection and nasal show that in the two administration methods of intravenous injection and nasal administration, under the same administration method, the time point of the system reaching the highest blood drug concentration is much higher than that of the original drug. The content of galantamine in plasma samples and tissue samples indicate that after intravenous administration and intranasal administration of the galantamine system, at the same time point, the drug concentration in brain tissue was far greater than that of the original drug of galantamine, and the duration was also longer. The concentration of drugs in brain tissue decreased gradually in the order of olfactory bulb, olfactory tract, brain, and cerebellum. In the brain tissues of the olfactory bulb, olfactory tract, cerebrum, and cerebellum, the drug concentration of the galantamine system after intravenous injection is lower than that after nasal administration., Conclusions: This study concludes that compared with the original drug solution, the nano drug delivery system has significant brain targeting for nasal administration, and intravenous injection also has brain targeting. In the olfactory bulb, olfactory tract, brain, and cerebellum, the brain targeting index at the olfactory bulb is the highest, and the targeting is the best.

Objective: To compare the effects of transurethral resection of the prostate (TURP) and transurethral columnar balloon dilatation of the prostate (TUCBDP) in the treatment of BPH., Methods: This study included 218 BPH patients treated in Qinhuangdao Workers' Hospital from July 2021 to November 2022, 109 by TURP and the other 109 by TUCBDP. We followed up the patients for 12 months, observed their postoperative recovery, complications, serum pain, inflammatory index, cytokine level, urodynamic index, symptom improvement and quality of life (QOL) and compared the data obtained between the two groups of patients., Results: At 12 months after surgery, the total effectiveness rate was significantly higher in the TUCBDP than in the TURP group (93.58% vs 84.40%, P< 0.05), and the postoperative recovery was better in the former than in the latter (P< 0.05). Compared with the baseline, the levels of serum prostaglandin E2 (PGE2), substance P, tumor necrosis factor-alpha (TNF-α) and high sensitive C-reactive protein (hs-CRP) were remarkably increased in both of the groups on the first day after surgery (P< 0.05), more significantly in the TURP than in the TUCBDP group (P< 0.05), while the levels of serum PSA and E2 decreased and the T level elevated in all the patients at 3 months postoperatively (P< 0.05), more significantly in the TUCBDP than in the TURP group (P< 0.05). Before and at 3 and 12 months after operation, the postvoid residual urine volume (PVR) and NIH-CPSI, IPSS and QOL scores showed a decreasing trend, while the maximum urinary flow rate (Qmax), maximum cystometric capacity (MCC) and maximum urethral closure pressure (MUCP) exhibited an increasing trend in both of the two groups, even more significantly in the TUCBDP than in the TURP group (P< 0.05)., Conclusion: TUCBDP is advantageous over TURP in promoting postoperative recovery, improving QOL, reducing postoperative pain, inflammation and complications, regulating the levels of serum cytokines, and improving urodynamics and clinical symptoms in BPH patients. However, with the extension of postoperative time, the two strategies are basically comparable in improving the urodynamics, symptoms and QOL of the patients.

Background: Our meta-analysis aimed to evaluate the diagnostic performance of 68 Ga-PSMA-11 PET/MRI for biochemical recurrence of prostate cancer., Methods: We systematically and comprehensively searched all available studies until May 2023 in the PubMed and Embase databases. Studies evaluating 68 Ga-PSMA-11 PET/MRI in men with prostate cancer biochemical recurrence were included. We appraised the quality of studies using a tailored Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. For each meta-analysis, we used the DerSimonian and Laird method. We first transformed proportions with the Freeman-Tukey double arcsine transformation, and then confidence intervals were calculated using the Jackson method. Meta-regression and sensitivity analysis were conducted to explore heterogeneity sources. Furthermore, we conducted subgroup analysis according to the PSA levels., Results: Overall, 13 studies with 738 patients were included in the analysis. The pooled overall detection rates of 68 Ga-PSMA-11 PET/MRI in detecting recurrent PCa after definitive treatment were 74% (95% CI, 68%-79%). For patients with PSA under 0.5 ng/mL, the detection rate was 55 %. The detection rates were 79 %, 76 % and 87 % for the subgroup PSA levels of 0.5-0.99, 1.0-1.99 and over 2.0 ng/mL., Conclusion: 68 Ga-PSMA-11 PET/MRI has a good detection rate for biochemical recurrence of prostate cancer. However, large sample, multi-center studies are still needed to verify and expand on our conclusion., (Copyright© 2024 Wang et al. Published by Tehran University of Medical Sciences.)

Cistanche deserticola is a precious Chinese medicinal material with extremely high health care and medicinal value. In recent years, the frequent occurrence of stem rot has led to reduced or even no harvests of C. deserticola. The unstandardized use of farm chemicals in the prevention and control processes has resulted in excessive chemical residues, threatening the fragile desert ecological environment. Therefore, it is urgent to explore safe and efficient prevention and control technologies. Biocontrol agents, with the advantages of safety and environment-friendliness, would be an important idea. The isolation, screening and identification of pathogens and antagonistic endophytic bacteria are always the primary basis. In this study, three novel pathogens causing C. deserticola stem rot were isolated, identified and pathogenicity tested, namely Fusarium solani CPF1, F. proliferatum CPF2, and F. oxysporum CPF3. For the first time, the endophytic bacteria in C. deserticola were isolated and identified, of which 37 strains were obtained. Through dual culture assay, evaluation experiment and tissue culture verification, a biocontrol candidate strain Bacillus atrophaeus CE6 with outstanding control effect on the stem rot was screened out. In the tissue culture system, CE6 showed excellent control effect against F. solani and F. oxysporum, with the control efficacies reaching 97.2% and 95.8%, respectively, indicating its great potential for application in the production. This study is of great significance for the biocontrol of plant stem rot and improvement of the yield and quality of C. deserticola., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

LEAP2 (liver expression antimicrobial peptide 2), is an antimicrobial peptide widely found in vertebrates and mainly expressed in liver. LEAP2 plays a vital role in host innate immunity. In teleosts, a number of LEAP2 homologs have been reported, but their in vivo effects on host defense are still limited. In this study, a LEAP2 homolog (SsLEAP2) was identified from black rockfish, Sebastes schlegelii, and its structure, expression as well as biological functions were analyzed. The results showed that the open reading frame of SsLEAP2 is 300 bp, with a 5'- untranslated region (UTR) of 375 bp and a 3' - UTR of 238 bp. The deduced amino acid sequence of SsLEAP2 shares the highest overall identity (96.97%) with LEAP2 of Sebastes umbrosus. SsLEAP2 possesses conserved LEAP2 features, including a signal peptide sequence, a prodomain and a mature peptide, in which four well-conserved cysteines formed two intrachain disulphide domain. The expression of SsLEAP2 was highest in liver and could be induced by experimental infection with Listonella anguillarum, Edwardsiealla piscicida and Rock bream iridovirus C1 (RBIV-C1). Recombinant SsLEAP2 (rSsLEAP2) purified from Escherichia coli was able to bind with various Gram-positive and Gram-negative bacteria. Further analysis showed that rSsLEAP2 could enhance the respiratory burst activity, and induce the expression of immune genes including interleukin 1-β (IL-1β) and serum amyloid A (SAA) in macrophages; additionally, rSsLEAP2 could also promote the proliferation and chemotactic of peripheral blood lymphocytes (PBLs). In vivo experiments indicated that overexpression of SsLEAP2 could inhibit bacterial infection, and increase the expression level of immune genes including IL-1β, tumor necrosis factor ligand superfamily member 13B (TNF13B) and haptoglobin (HP); conversely, knock down of SsLEAP2 promoted bacterial infection and decreased the expression level of above genes. Taken together, these results suggest that SsLEAP2 is a novel LEAP2 homolog that possesses apparent antibacterial activity and immunoregulatory property, thus plays a critical role in host defense against pathogens invasion., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Prolyl hydroxylase domain 2 (PHD2) is an important enzyme in the human body that perceives changes in oxygen concentration and regulates response in hypoxic environments. Evaluation of PHD2 inhibitory activity of natural products is crucial for drug development of hypoxia related diseases. At present, the detection of low concentration of α-ketoglutaric acid (the substrate of PHD2 enzymatic reaction) requires derivatization reactions or sample pretreatment, which undoubtedly increases the workload of PHD2 inhibitory activity evaluation. In this paper, a direct detection approach of α-ketoglutaric acid was established by using the online stacking strategy of capillary electrophoresis to evaluate the PHD2 inhibitory activity of natural products. Under optimized conditions, detection of a single sample can be achieved within 2 min. By calculation, the intraday precision RSD of the apparent electrophoretic mobility and peak areas of α-ketoglutaric acid are 0.92 % and 0.79 %, respectively, and the interday RSD were 1.27 % and 0.96 % respectively. The recoveries of the present approach were 97.9-105.2 %, and the LOQ and LOD were 2.0 μM and 5.0 μM, respectively. Furthermore, this approach was applied for the evaluation of inhibitory activity of PHD2 for 13 natural products, and PHD2 inhibitory activity of salvianolic acid A was firstly reported. The present work not only realizes evaluation of PHD2 inhibitory activity through direct detection of α-ketoglutaric acid, but also provides technical support for the discovery of potential drug molecules in hypoxia related diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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.

The sluggish kinetics of the oxygen evolution reaction (OER) always results in a high overpotential at the anode of water electrolysis and an excessive electric energy consumption, which has been a major obstacle for hydrogen production through water electrolysis. In this study, we present a CoNi-LDH/Fe MOF/NF heterostructure catalyst with nanoneedle array morphology for the OER. In 1.0 M KOH solution, the heterostructure catalyst only required overpotentials of 275 and 305 mV to achieve high current densities of 500 and 1000 mA/cm 2 for OER, respectively. The catalytic activities are much higher than those of the reference single-component CoNi-LDH/NF and Fe MOF/NF catalysts. The improved catalytic performance of the heterostructure catalyst can be ascribed to the synergistic effect of CoNi-LDH and Fe MOF. In particular, when the anodic OER is replaced with the urea oxidation reaction (UOR), which has a relatively lower thermodynamic equilibrium potential and is expected to reduce the cell voltage, the overpotentials required to achieve the same current densities can be reduced by 80 and 40 mV, respectively. The cell voltage required to drive overall urea splitting (OUS) is only 1.55 V at 100 mA/cm 2 in the Pt/C/NF||CoNi-LDH/Fe MOF/NF two-electrode electrolytic cell. This value is 60 mV lower compared with that required for overall water splitting (OWS). Our results indicate that a reasonable construction of a heterostructure catalyst can significantly give rise to higher electrocatalytic performance, and using UOR to replace the anodic OER of the OWS can greatly reduce the electrolytic energy consumption.

Background: The genus Macrosemia Kato, 1925 (Hemiptera, Cicadidae, Cicadinae, Dundubiini, Dundubiina) currently includes 16 species (excluding subspecies and varieties), mainly occurring in the Oriental Region. More than half of them, 10 species, are known from China, including one new species, described in the present study., New Information: A new species of cicada, Macrosemiafengi Wang sp. nov. , is described from Yunnan and Guizhou, southwest China. Colour plates are presented to illustrate its diagnostic characters. The distribution map of the new species is also given., (Cheng-Bin Wang.)

Background: The genus Tanna Distant, 1905 (Hemiptera, Cicadidae, Cicadinae, Leptopsaltriini, Leptopsaltriina) currently includes 23 species (three tentatively placed), with its actual geographical distribution in China, Japan, Nepal, Bhutan, Cambodia, Thailand and Vietnam. Most of them, 16 species, are known from China, including one new species here described., New Information: A new species of cicada, Tannafengi Wang sp. nov. , is described from Yunnan, southwest China. Colour plates are presented to illustrate all diagnostic characters. An updated list of Tanna species occurring in China is provided., (Cheng-Bin Wang.)

Sunflower ( Helianthus annuus L.) is cultivated around the world as an oil crop, and its receptacle is the byproduct and is usually deemed to be an agro-industrial waste. Then, phytochemical constituents and antifungal bioactivity of the sunflower receptacle against phytopathogenic fungi were investigated. As a result, 17 diterpenoids including 4 new compounds were isolated, and most of them showed potential antifungal activity against Botrytis cinerea , in which compounds 1 , 3 , 5 , and 15 exhibited better inhibitory effect with the minimum inhibitory concentration values of 0.05-0.1 mg/mL. Meanwhile, four antifungal diterpenoids destructed plasma membrane integrity, suspended the biofilm formation ability, and increased the extravasation of cellular contents of B. cinerea . Moreover, the EtOAc extract of sunflower receptacle could keep 42.9% of blueberries from the invasion of B. cinerea at 1.6 mg/mL. The finding suggested that sunflower receptacle might be a biocontrol agent for preventing fruit from postharvest diseases.

Background: The purpose of the study was to develop a genotype-incorporated population pharmacokinetic (PPK) model of tacrolimus (TAC) in adults with systemic lupus erythematosus (SLE) to investigate the factors influencing TAC pharmacokinetics and to develop an individualized dosing regimen based on the model. In addition, a non-genotype-incorporated model was also established to assess its predictive performance compared to the genotype-incorporated model., Methods: A total of 365 trough concentrations from 133 adult SLE patients treated with TAC were collected to develop a genotype-incorporated PPK model and a non-genotype-incorporated PPK model of TAC using a nonlinear mixed-effects model (NONMEM). External validation of the two models was performed using data from an additional 29 patients. Goodness-of-fit diagnostic plots, bootstrap method, and normalized predictive distribution error test were used to validate the predictive performance and stability of the final models. The goodness-of-fit of the two final models was compared using the Akaike information criterion (AIC). The dosing regimen was optimized using Monte Carlo simulations based on the developed optimal model., Results: The typical value of the apparent clearance (CL/F) of TAC estimated in the final genotype-incorporated model was 14.3 L h -1 with inter-individual variability of 27.6%. CYP3A5 polymorphism and coadministered medication were significant factors affecting TAC-CL/F. CYP3A5 rs776746 GG genotype carriers had only 77.3% of the TAC-CL/F of AA or AG genotype carriers. Omeprazole reduced TAC-CL/F by 3.7 L h -1 when combined with TAC, while TAC-CL/F increased nonlinearly as glucocorticoid dose increased. Similar findings were demonstrated in the non-genotype-incorporated PPK model. Comparing these two models, the genotype-incorporated PPK model was superior to the non-genotype-incorporated PPK model (AIC = 643.19 vs. 657.425). Monte Carlo simulation based on the genotype-incorporated PPK model indicated that CYP3A5 rs776746 AA or AG genotype carriers required a 1/2-1 fold higher dose of TAC than GG genotype carriers to achieve the target concentration. And as the daily dose of prednisone increases, the dose of TAC required to reach the target concentration increases appropriately., Conclusions: We developed the first pharmacogenetic-based PPK model of TAC in adult patients with SLE and proposed a dosing regimen based on glucocorticoid dose and CYP3A5 genotype according to the model, which could facilitate individualized dosing for TAC., 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. Published by Elsevier B.V.)

The diffuse Galactic γ-ray emission, mainly produced via interactions between cosmic rays and the interstellar medium and/or radiation field, is a very important probe of the distribution, propagation, and interaction of cosmic rays in the Milky Way. In this Letter, we report the measurements of diffuse γ rays from the Galactic plane between 10 TeV and 1 PeV energies, with the square kilometer array of the Large High Altitude Air Shower Observatory (LHAASO). Diffuse emissions from the inner (15°10  TeV). The energy spectrum in the inner Galaxy regions can be described by a power-law function with an index of -2.99±0.04, which is different from the curved spectrum as expected from hadronic interactions between locally measured cosmic rays and the line-of-sight integrated gas content. Furthermore, the measured flux is higher by a factor of ∼3 than the prediction. A similar spectrum with an index of -2.99±0.07 is found in the outer Galaxy region, and the absolute flux for 10≲E≲60  TeV is again higher than the prediction for hadronic cosmic ray interactions. The latitude distributions of the diffuse emission are consistent with the gas distribution, while the longitude distributions show clear deviation from the gas distribution. The LHAASO measurements imply that either additional emission sources exist or cosmic ray intensities have spatial variations.

In situ mitochondrial oxidative stress amplification is an effective strategy to improve efficacy of cancer treatment. In this work, a tumor and mitochondria dual-targeted multifunctional nanoplatform CMS@AIPH@PDA@COTPP@FA (CAPCTF) was prepared, in which a thermally decomposable radical initiator AIPH was loaded inside the mesoporores of Cu x Mo y S z (CMS) nanoparticles with polydopamine (PDA) covered films that were further covalently functionalized by a mitochondria-targeted CO donor (COTPP) and a directing group of folic acid (FA). The prepared CAPCTF nanoplatform selectively accumulated in cancer cells and further targeted the mitochondrial organelle where carbon monoxide (CO) and O 2 -independent free radicals (•OH/•R) were in situ generated upon 1064 nm laser irradiation. Furthermore, the CMS nanocarrier was capable of depleting the GSH overexpressed in the tumor microenvironment (TME), thus preventing free radical scavenging. As a result, the CAPCTF nanoplatform exhibited outstanding in vitro and in vivo antitumor efficacy under hypoxic conditions. This provides an innovative strategy that combines O 2 -independent free radicals (•OH/•R) generation, CO delivery and GSH consumption to amplify intracellular oxidative stresses and induce mitochondrial dysfunction, thus leading to cancer cells eradication, which may have significant implications for personalized hypoxic tumor treatment., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

A new species of the genus Synochoneura Obraztsov, 1955, S. wuyishana sp. nov. is described and illustrated from Wuyishan National Park in Fujian Province of China. The new species resembles S. sapana, but differs in wing pattern and female genitalia characters. Illustrations of adults and genitalia are provided. Additionally, a key to the Chinese Synochoneura species based on morphology is presented. The type specimens are deposited in the Department of Entomology, College of Plant Protection, South China Agricultural University, Guangzhou.

Sixteen new quinolizidine alkaloids (QAs), named ormosianines A-P ( 1 - 16 ), and 18 known congeners ( 17 - 34 ) were isolated from the stems and leaves of Ormosia yunnanensis . The structures were elucidated based on spectroscopic analyses and electron circular dichroism (ECD) calculations. Structurally, ormosianines A ( 1 ) and B ( 2 ) are the first examples of cytisine and Ormosia- type alkaloids with the cleavage of the piperidine ring. Results of the acetylcholinesterase (AChE) inhibitory assay revealed that the pentacycline Ormosia- type QAs, including 1 , 16 , 24 , and 27 - 29 , are good AChE inhibitors. Ormosianine A ( 1 ) exhibited more potent AChE inhibitory activity with an IC 50 value of 1.55 μM. Molecular docking revealed that 1 might bind to the protein 1DX4, forming two hydrogen bonds with residues SER-238 and HIS-480.

Penetrating head injury is a serious open cranial injury. In civilians, it is often caused by non-missile, low velocity flying objects that penetrate the skull through a weak cranial structure, forming intracranial foreign bodies. The intracranial foreign body can be displaced due to its special quality, shape, and location. In this paper, we report a rare case of right-to-left displacement of an airgun lead bullet after transorbital entry into the skull complicated by posttraumatic epilepsy, as a reminder to colleagues that intracranial metal foreign bodies maybe displaced intraoperatively. In addition, we have found that the presence of intracranial metallic foreign bodies may be a factor for the posttraumatic epilepsy, and their timely removal appears to be beneficial for epilepsy control.

The potential application of borophene as a sensing material for gas-sensing devices is investigated in this work. We utilize density functional theory (DFT) to systematically study the adsorption mechanism and sensing performance of χ 3 -borophene to search for high-sensitivity sensors for minor pollutant gases. We compare the results to those for two Pmmn borophenes. The first-principles calculations are used to analyze the sensing performance of the three different borophenes (2 Pmmn borophene, 8 Pmmn borophene, and χ 3 -borophene) on five leading harmful gases (CO, NH 3 , SO 2 , H 2 S, and NO 2 ). The adsorption configuration, adsorption energy, and electronic properties of χ 3 -borophene are investigated. Our results indicate that the mechanism of adsorption on χ 3 -borophene is chemisorption for NO 2 and physisorption for SO 2 and H 2 S. The mode of adsorption of CO and NH 3 on χ 3 -borophene can be both physisorption and chemisorption, depending on the initially selected sites. Analyses of the charge transfer and density of states show that χ 3 -borophene is selective toward the adsorption of harmful gases and that N and O atoms form covalent bonds when chemisorbed on the surface of χ 3 -borophene. An interesting phenomenon is that when 8 Pmmn borophene adsorbs SO 2 , the gas molecules are dismembered and strongly adsorb on the surface of 8 Pmmn borophene, which provides a way of generating O 2 while adsorbing harmful substances. Overall, the results of this work demonstrate the potential applications of borophene as a sensing material for harmful gas sensing or removal.

Zanthoxylum armatum DC. is an important medicinal plant, and its pericarps are commonly used as a natural spice in Asian countries. In this study, fifteen alkylamides were isolated and elucidated from the pericarps of Z. armatum, including five undescribed alkylamides (1-5) and ten known compounds (6-15). The molecular structures of all compounds were elucidated by 1D and 2D NMR spectroscopic analysis and mass spectrometry, among which the absolute configuration of compound 15 was determined by the Mo 2 (OAc) 4 -induced circular dichroism method. Moreover, all compounds were screened for their neuroprotective activity against H 2 O 2 -induced oxidative stress in human neuroblastoma SH-SY5Y cells for the evaluation of their neuroprotective activity. Especially, compounds 2-4 expressed potential neuroprotective activity, and further research showed that the cell viability was significantly enhanced in a concentration dependent manner when the cells were treated for 6 h. Moreover, compounds 2-4 could decrease reactive oxygen species accumulation. This paper enriched structure types of alkylamides in Zanthoxylum armatum., 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.)

Background and Objectives: Tacrolimus (TAC) has been increasingly used in patients with non-transplant settings. Because of its large between-subject variability, several population pharmacokinetic (PPK) studies have been performed to facilitate individualized therapy. This review summarized published PPK models of TAC in non-transplant patients, aiming to clarify factors affecting PKs of TAC and identify the knowledge gap that may require further research., Methods: The PubMed, Embase databases, and Cochrane Library, as well as related references, were searched from the time of inception of the databases to February 2023, to identify TAC population pharmacokinetic studies modeled in non-transplant patients using a non-linear mixed-effects modeling approach., Results: Sixteen studies, all from Asian countries (China and Korea), were included in this study. Of these studies, eleven and four were carried out in pediatric and adult patients, respectively. One-compartment models were the commonly used structural models for TAC. The apparent clearance (CL/F) of TAC ranged from 2.05 to 30.9 L·h -1 (median of 14.9 L·h -1 ). Coadministered medication, genetic factors, and weight were the most common covariates affecting TAC-CL/F, and variability in the apparent volume of distribution (V/F) was largely explained by weight. Coadministration with Wuzhi capsules reduced CL/F by about 19 to 43%. For patients with CYP3A5*1*1 and *1*3 genotypes, the CL/F was 39-149% higher CL/F than patients with CYP3A5*1*1., Conclusion: The optimal TAC dosage should be adjusted based on the patient's co-administration, body weight, and genetic information (especially CYP3A5 genotype). Further studies are needed to assess the generalizability of the published models to other ethnic groups. Moreover, external validation should be frequently performed to improve the clinical practicality of the models., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Some gamma-ray bursts (GRBs) have a tera-electron volt (TeV) afterglow, but the early onset of this has not been observed. We report observations with the Large High Altitude Air Shower Observatory (LHAASO) of the bright GRB 221009A, which serendipitously occurred within the instrument's field of view. More than 64,000 photons >0.2 TeV were detected within the first 3000 seconds. The TeV flux began several minutes after the GRB trigger and then rose to a peak ~10 seconds later. This was followed by a decay phase, which became more rapid ~650 seconds after the peak. We interpret the emission using a model of a relativistic jet with half-opening angle of ~0.8°. This is consistent with the core of a structured jet and could explain the high isotropic energy of this GRB.