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Objective: In this study, we aim to explore the genetic imprint of Bronze Age globalization in East Asia from a phylogeographic perspective by examining the Y-chromosome haplogroup Q1a1a-M120, and to identify key demographic processes involved in the formation of early China and the ancient Huaxia people., Methods: Over the past few decades, we have collected the sequences of 347 Y chromosomes from the haplogroup Q1a1a-M120. These sequences were utilized to analyze and reconstruct a highly revised phylogenetic tree with age estimates. And we analyzed the geographical distribution and spatial autocorrelation of nine major sub-branches of Q1a1a-M120. Finally, we observed the expansion of Q1a1a-M120 from the beginning of the Bronze Age in East Asia, along with the continuous dissemination of its sub-lineages among East Asian populations., Results: We suggest that certain sub-lineages played a significant role in the formation of states and early civilizations in China, as well as in the development of the ancient Huaxia people, who are the direct ancestors of the Han population. Overall, we propose that haplogroup Q-M120 played a role in the introduction of Bronze Age culture to the central region of East Asia. Therefore, it is haplogroup Q-M120, rather than the Western Eurasian paternal lineage, that expanded and contributed to the gene pool of the East Asian population., Conclusion: In summary, the globalization of the Bronze Age led to large-scale population replacement and admixture across various regions of Eurasia; our findings highlight the unique demographic processes that occurred in East Asia during this period., (© 2024 University College London (UCL) and John Wiley & Sons Ltd.)

Aberrant inorganic phosphate (Pi) homeostasis causes brain calcification and aggravates neurodegeneration, but the underlying mechanism remains unclear. Here, we found that primary familial brain calcification (PFBC)-associated Pi transporter genes Pit2 and Xpr1 were highly expressed in astrocytes, with importer PiT2 distributed over the entire astrocyte processes and exporter XPR1 localized to astrocyte end-feet on blood vessels. This polarized PiT2 and XPR1 distribution endowed astrocyte with Pi transport capacity competent for brain Pi homeostasis, which was disrupted in mice with astrocyte-specific knockout (KO) of either Pit2 or Xpr1. Moreover, we found that Pi uptake by PiT2, and its facilitation by PFBC-associated galactosidase MYORG, were required for the high Pi transport capacity of astrocytes. Finally, brain calcification was suppressed by astrocyte-specific PiT2 re-expression in Pit2-KO mice. Thus, astrocyte-mediated Pi transport is pivotal for brain Pi homeostasis, and elevating astrocytic Pi transporter function represents a potential therapeutic strategy for reducing brain calcification., Competing Interests: Declaration of interests X.C., Z.-Q.X., W.-J.C. M.Z., C.W.H., and L.C. have filed a patent [CN2023108906808] for the therapeutic application of astrocyte-targeted replacement gene expression., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Primary familial brain calcification (PFBC) is a genetic neurological disease, yet no effective treatment is currently available. Here, we identified five novel intronic variants in SLC20A2 gene from six PFBC families. Three of these variants increased aberrant SLC20A2 pre-mRNA splicing by altering the binding affinity of splicing machineries to newly characterized cryptic exons, ultimately causing premature termination of SLC20A2 translation. Inhibiting the cryptic-exon incorporation with splice-switching ASOs increased the expression levels of functional SLC20A2 in cells carrying SLC20A2 mutations. Moreover, by knocking in a humanized SLC20A2 intron 2 sequence carrying a PFBC-associated intronic variant, the SLC20A2-KI mice exhibited increased inorganic phosphate (Pi) levels in cerebrospinal fluid (CSF) and progressive brain calcification. Intracerebroventricular administration of ASOs to these SLC20A2-KI mice reduced CSF Pi levels and suppressed brain calcification. Together, our findings expand the genetic etiology of PFBC and demonstrate ASO-mediated splice modulation as a potential therapy for PFBC patients with SLC20A2 haploinsufficiency., Competing Interests: Declaration of interests W.-J.C., Z.-Q.X., X.C., M.Z., Y.-H.Z., and L.C. have filed patents (CN2023113708968) to protect the application of CRACE therapy for the treatment of brain calcification., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: To identify mtDNA and OGG1 as potential biomarker candidates for mechanical asphyxia., Method: The human tissues are divided into experimental group (hanging and strangulation) and control groups (hemorrhagic shock, brain injury group, and poisoning group). Detected the expression of OGG1 and integrity of mtDNA in cardiac tissue of each group. We used over-OGG1 vector and siRNA-OGG1 transfecting H9C2 cell line to observe the function of OGG1 in hypoxic cells., Results: 1. mtDNA integrity decreased in the mechanical asphyxia group, OGG1 expression increased in mechanical asphyxia groups. They can be biomarkers for mechanical asphyxia. 2. OGG1 increased first and decreased in hypoxia-induced H9C2 cells. OGG1 upregulated the TFAM, NRF1, and Bcl2 in hypoxia-induced H9C2. OGG1 downregulated cleaved-Caspase3 in hypoxia-induced H9C2 cells. 3. In the normoxia condition, NAC maintained mtDNA integrity and decreased the mitochondrial membrane potential and amount of ATP., Conclusion: mtDNA integrity and OGG1 expression can be biomarkers for mechanical asphyxia. OGG1 can maintain mtDNA integrity and maintain the stability of the mitochondrial membrane., 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.)

Objective: Most paroxysmal kinesigenic dyskinesia (PKD) cases are hereditary, yet approximately 60% of patients remain genetically undiagnosed. We undertook the present study to uncover the genetic basis for undiagnosed PKD patients., Methods: Whole-exome sequencing was performed for 106 PRRT2-negative PKD probands. The functional impact of the genetic variants was investigated in HEK293T cells and Drosophila., Results: Heterozygous variants in KCNJ10 were identified in 11 individuals from 8 unrelated families, which accounted for 7.5% (8/106) of the PRRT2-negative probands. Both co-segregation of the identified variants and the significantly higher frequency of rare KCNJ10 variants in PKD cases supported impacts from the detected KCNJ10 heterozygous variants on PKD pathogenesis. Moreover, a KCNJ10 mutation-carrying father from a typical EAST/SeSAME family was identified as a PKD patient. All patients manifested dystonia attacks triggered by sudden movement with a short episodic duration. Patch-clamp recordings in HEK293T cells revealed apparent reductions in K + currents of the patient-derived variants, indicating a loss-of-function. In Drosophila, milder hyperexcitability phenotypes were observed in heterozygous Irk2 knock-in flies compared to homozygotes, supporting haploinsufficiency as the mechanism for the detected heterozygous variants. Electrophysiological recordings showed that excitatory neurons in Irk2 haploinsufficiency flies exhibited increased excitability, and glia-specific complementation with human Kir4.1 rescued the Irk2 mutant phenotypes., Interpretation: Our study established haploinsufficiency resulting from heterozygous variants in KCNJ10 can be understood as a previously unrecognized genetic cause for PKD and provided evidence of glial involvement in the pathophysiology of PKD. ANN NEUROL 2024., (© 2024 American Neurological Association.)

Acupoint drug delivery is a traditional external therapy of traditional Chinese medicine(TCM). Guided by the meridian and collateral theory in TCM, it applies medications to the skin at acupoints, exerting a dual therapeutic effect by stimulating the acupoints and the conduction of meridians. Acupoint drug delivery is widely used in clinical practice. Different from traditional oral admi-nistration and injection, it absorbs medications through the skin, effectively avoiding the first-pass effect of drugs and the toxic side effects caused by injection. Acupoint selection and transdermal drug absorption are pivotal factors affecting the efficacy of acupoint drug delivery. Recent research on acupoint drug delivery mainly focuses on the evaluation of clinical efficacy, yet the systematic investigations on acupoint selection and pharmacodynamic factors are scarce. This study reviews the mechanism, efficacy evaluation and application status of acupoint drug delivery. It integrates the theory of TCM with modern medicine to explore the mechanism of acupoint drug delivery, evaluate its clinical efficacy, and assess the transdermal penetration in vivo and in vitro. The application status of acupoint drug delivery is also summarized, including the selection of acupoints, application dosage form, application time and the absorption of acupoints. This review aims to offer insights and references for the research, development and clinical application of acupoint drug delivery products.

Objectives: To investigate the age-related changes of the mandibular third molar root pulp visibility in individuals in East China, and to explore the feasibility of applying this method to determine whether an individual is 18 years or older., Methods: A total of 1 280 oral panoramic images were collected from the 15-30 years old East China population, and the mandibular third molar root pulp visibility in all oral panoramic images was evaluated using OLZE 0-3 four-stage method, and the age distribution of the samples at each stage was analyzed using descriptive statistics., Results: Stages 0, 1, 2 and 3 first appeared in 16.88, 19.18, 21.91 and 25.44 years for males and in 17.47, 20.91, 22.01 and 26.01 years for females. In all samples, individuals at stages 1 to 3 were over 18 years old., Conclusions: It is feasible to determine whether an individual in East China is 18 years or older based on the mandibular third molar root pulp visibility on oral panoramic images.

Thyroid storm is an acute life-threatening condition of hyperthyroidism that can present with cardiac failure, requiring extracorporeal membrane oxygenation (ECMO). We present the first case reported of total thyroidectomy successfully performed while on ECMO for thyroid storm in a 32-year-old male. This case highlights the challenges of managing refractory thyroid storm with multi-organ failure. We demonstrate that total thyroidectomy may still be safely performed while on ECMO for thyroid storm, if steps are taken to optimise the patient perioperatively, with careful surgical and anaesthesia planning., Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-04430-9., Competing Interests: Competing InterestsThe authors declare that they have no competing interest., (© Association of Otolaryngologists of India 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

COPD poses a significant global public health challenge, primarily characterised by irreversible airflow restriction and persistent respiratory symptoms. The hallmark pathology of COPD includes sustained airway inflammation and the eventual destruction of lung tissue structure. While multiple risk factors are implicated in the disease's progression, the underlying mechanisms remain largely elusive. The perpetuation of inflammation is pivotal to the advancement of COPD, emphasising the importance of investigating these self-sustaining mechanisms for a deeper understanding of the pathogenesis. Autoimmune responses constitute a critical mechanism in maintaining inflammation, with burgeoning evidence pointing to their central role in COPD progression; yet, the intricacies of these mechanisms remain inadequately defined. This review elaborates on the evidence supporting the presence of autoimmune processes in COPD and examines the potential mechanisms through which autoimmune responses may drive the chronic inflammation characteristic of the disease. Moreover, we attempt to interpret the clinical manifestations of COPD through autoimmunity., Competing Interests: Conflict of interest: L-L Dong, Z-Y. Liu, K-J. Chen, Z-Y. Li, J-S. Zhou, H-H. Shen and Z-H. Chen 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 ©The authors 2024.)

The extracellular superoxide dismutases (ecSODs) secreted by Microplitis bicoloratus reduce the reactive oxygen species (ROS) stimulated by the Microplitis bicoloratus bracovirus . Here, we demonstrate that the bacterial transferase hexapeptide (hexapep) motif and bacterial-immunoglobulin-like (BIg-like) domain of ecSODs bind to the cell membrane and transiently open hemichannels, facilitating ROS reductions. RNAi-mediated ecSOD silencing in vivo elevated ROS in host hemocytes, impairing parasitoid larva development. In vitro , the ecSOD-monopolymer needed to be membrane bound to open hemichannels. Furthermore, the hexapep motif in the beta-sandwich of ecSOD49 and ecSOD58, and BIg-like domain in the signal peptides of ecSOD67 were required for cell membrane binding. Hexapep motif and BIg-like domain deletions induced ecSODs loss of adhesion and ROS reduction failure. The hexapep motif and BIg-like domain mediated ecSOD binding via upregulating innexins and stabilizing the opened hemichannels. Our findings reveal a mechanism through which ecSOD reduces ROS, which may aid in developing anti-redox therapy., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Background: Hereditary spastic paraplegias (HSP) are neurologic disorders characterized by progressive lower-extremity spasticity. Despite the identification of several HSP-related genes, many patients lack a genetic diagnosis., Objectives: The aims were to confirm the pathogenic role of biallelic COQ4 mutations in HSP and elucidate the clinical, genetic, and functional molecular features of COQ4-associated HSP., Methods: Whole exome sequences of 310 index patients with HSP of unknown cause from three distinct populations were analyzed to identify potential HSP causal genes. Clinical data obtained from patients harboring candidate causal mutations were examined. Functional characterization of COQ4 variants was performed using bioinformatic tools, single-cell RNA sequencing, biochemical assays in cell lines, primary fibroblasts, induced pluripotent stem cell-derived pyramidal neurons, and zebrafish., Results: Compound heterozygous variants in COQ4, which cosegregated with HSP in pedigrees, were identified in 7 patients from six unrelated families. Patients from four of the six families presented with pure HSP, whereas probands of the other two families exhibited complicated HSP with epilepsy or with cerebellar ataxia. In patient-derived fibroblasts and COQ4 knockout complementation lines, stable expression of these missense variants exerted loss-of-function effects, including mitochondrial reactive oxygen species accumulation, decreased mitochondrial membrane potential, and lower ubiquinone biosynthesis. Whereas differentiated pyramidal neurons expressed high COQ4 levels, coq4 knockdown zebrafish displayed severe motor dysfunction, reflecting motor neuron dysregulation., Conclusions: Our study confirms that loss-of-function, compound heterozygous, pathogenic COQ4 variants are causal for autosomal recessive pure and complicated HSP. Moreover, reduced COQ4 levels attributable to variants correspond with decreased ubiquinone biosynthesis, impaired mitochondrial function, and higher phenotypic disease severity. © 2023 International Parkinson and Movement Disorder Society., (© 2023 International Parkinson and Movement Disorder Society.)

Status epilepticus (SE) is a life-threatening disorder that can result in death or severe brain damage, and there is a substantial body of evidence suggesting a strong association between pyroptosis and SE. Sterol regulatory element binding protein 1 (SREBP1) is a significant transcription factor participating in both lipid homeostasis and glucose metabolism. However, the function of SREBP1 in pyroptosis during SE remains unknown. In this study, we established a SE rat model by intraperitoneal injection of lithium chloride and pilocarpine in vivo. Additionally, we treated HT22 hippocampal cells with glutamate to create neuronal injury models in vitro. Our results demonstrated a significant induction of SREBP1, inflammasomes, and pyroptosis in the hippocampus of SE rats and glutamate-treated HT22 cells. Moreover, we found that SREBP1 is regulated by the mTOR signaling pathway, and inhibiting mTOR signaling contributed to the amelioration of SE-induced hippocampal neuron pyroptosis, accompanied by a reduction in SREBP1 expression. Furthermore, we conducted siRNA-mediated knockdown of SREBP1 in HT22 cells and observed a significant reversal of glutamate-induced cell death, activation of inflammasomes, and pyroptosis. Importantly, our confocal immunofluorescence analysis revealed the co-localization of SREBP1 and NLRP1. In conclusion, our findings suggest that deficiency of SREBP1 attenuates glutamate-induced HT22 cell injury and hippocampal neuronal pyroptosis in rats following SE. Targeting SREBP1 may hold promise as a therapeutic strategy for SE., Competing Interests: 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., (© 2023 The Authors. Published by Elsevier Ltd.)

Parasitoid wasps control pests via a precise attack leading to the death of the pest. However, parasitoid larvae exhibit self-protection strategies against bracovirus-induced reactive oxygen species impairment. This has a detrimental effect on pest control. Here, we report a strategy for simulating Microplitis bicoloratus bracovirus using Mix-T dsRNA targeting 14 genes associated with transcription, translation, cell-cell communication, and humoral signaling pathways in the host, and from wasp extracellular superoxide dismutases. We implemented either one-time feeding to the younger instar larvae or spraying once on the corn leaves, to effectively control the invading pest Spodoptera frugiperda . This highlights the conserved principle of "biological pest control," as elucidated by the triple interaction of parasitoid-bracovirus-host in a cooperation strategy of bracovirus against its pest host., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Ma, Long, Yan, Peng, Cai, Zhong, Huang, Qiao, Zhou, Cai, Cheng, Zhou, Han, Liu, Zhang, Tang, Meng and Luo.)

Catecholamines (CAs) are aromatic amines containing a 3,4-dihydroxyphenyl nucleus and an amine side chain. Representative CAs included the endogenous neurotransmitters epinephrine, norepinephrine, and dopamine. CAs and their derivatives are good resources for the development of sympathomimetic or central nervous system drugs, while they also provide ligands important for G-protein coupled receptor (GPCR) research. CAs are of broad interest in the fields of chemical, biological, medical, and material sciences due to their high adhesive capacities, chemical reactivities, metal-chelating abilities, redox activities, excellent biocompatibilities, and ease of degradability. Herein, we summarize CAs derivatives isolated and identified from microorganisms, plants, insects, and marine invertebrates in recent decades, alongside their wide range of reported biological activities. The aim of this review is to provide an overview of the structural and biological diversities of CAs, the regularity of their natural occurrences, and insights toward future research and development pertinent to this important class of naturally occurring compounds.

Objectives: Previous studies suggested that the Y-chromosome haplogroups O2-N6-B451-AM01756 and O1a-M119 are two founder lineages of proto-Austronesians at about five thousand years ago. The objective of this study was to investigate the formation of proto-Austronesians from the perspective of the paternal gene pool., Materials and Methods: In this study, we developed a highly evised phylogenetic tree with age estimates for haplogroup O2-N6 and early branches of O1a-M119 (M110, F1036, and F819). In addition, we also explored the geographical distribution of eight sub-branches of O2-N6 and O1a-M119, and spatial autocorrelation analysis was conducted for each sub-branch., Results: The paternal lineage combination of proto-Austronesians is a small subset of a diverse gene pool of populations from the mainland of East Asia. The distribution map and results of the spatial autocorrelation analysis suggested that the eastern coastal region of northern China is likely the source of lineage O2-N6 while the coastal region of southeastern China is likely the diffusion center of early branches of O1a-M119. We developed an evolutionary diagram for Austronesians and their ancestors in the past 18,000 years., Discussion: We proposed that the millet farming community in North China is the common ancestor group of the Austronesians and the Han people, while the diverse ancient people in the southeast coastal areas of East Asia form the common ancestor group of the Austronesians and the East Asian mainland population. The demographic history of multiple ancestral groups of the most recent common ancestor group itself in the more ancient period is helpful to understand the deep roots of the genetic components and cultural traditions of Austronesians., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Diabetic patients receiving the antidiabetic drug metformin have been observed to exhibit a lower prevalence of anxiety disorders, yet the precise mechanism behind this phenomenon is unclear. In our study, we found that anxiety induces a region-specific reduction in AMPK activity in the medial prefrontal cortex (mPFC). Concurrently, transgenic mice with brain-specific AMPK knockout displayed abnormal anxiety-like behaviors. Treatment with metformin or the overexpression of AMPK restored normal AMPK activity in the mPFC and mitigated social stress-induced anxiety-like behaviors. Furthermore, the specific genetic deletion of AMPK in the mPFC not only instigated anxiety in mice but also nullified the anxiolytic effects of metformin. Brain slice recordings revealed that GABAergic excitation and the resulting inhibitory inputs to mPFC pyramidal neurons were selectively diminished in stressed mice. This reduction led to an excitation-inhibition imbalance, which was effectively reversed by metformin treatment or AMPK overexpression. Moreover, the genetic deletion of AMPK in the mPFC resulted in a similar defect in GABAergic inhibitory transmission and a consequent hypo-inhibition of mPFC pyramidal neurons. We also generated a mouse model with AMPK knockout specific to GABAergic neurons. The anxiety-like behaviors in this transgenic mouse demonstrated the unique role of AMPK in the GABAergic system in relation to anxiety. Therefore, our findings suggest that the activation of AMPK in mPFC inhibitory neurons underlies the anxiolytic effects of metformin, highlighting the potential of this primary antidiabetic drug as a therapeutic option for treating anxiety disorders., (© 2023. The Author(s).)

Objectives: In previous reports, proton pump inhibitor (PPI) use increased the risk of gout. However, there is no epidemiological study investigating this association. We aimed to examine the potential impact of PPI treatment on the risk of developing gout., Methods: A population-based case-control study was performed using a Longitudinal Health Insurance Database 2000 from Taiwan (population 23 million). We identified gout cases and non-gout controls through propensity score matching at 1:1, which was matched by sex and age. We used a conditional logistic regression model to estimate an odds ratio and 95% confidence intervals (CI) for gout population versus controls., Results: Esomeprazole increased the risk of gout after adjusting confounding variables (adjusted odds ratio [aOR] 1.3; 95% CI 1.0-1.6). The risk of gout was highest within 30 days of PPI treatment (aOR 1.7; 95% CI 1.4-1.9) and attenuated thereafter. The risk of gout was increased among female users of PPI compared with male users (aOR 2.2; 95% CI 1.7-2.8). The aOR of gout in people with PPI use was higher in middle-aged individuals (41-60 years: aOR 2.1; 95% CI 1.7-2.7) than in the older group (≥60 years: aOR 1.8; 95% CI 1.5-2.2)., Conclusions: Our findings provide population-level evidence for the hypothesis that PPI treatment is positively associated with the risk of developing gout. Further research on the mechanism underlying this association is warranted., (© 2023 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Previous studies demonstrated Y chromosome haplogroup C2a-M48-SK1061 is the only founding paternal lineage of all Tungusic-speaking populations. To infer the differentiation history of these populations, we studied more sequences and constructed downstream structure of haplogroup C2a-M48-SK1061 with better resolution. In this study, we generated 100 new sequences and co-analyzed 140 sequences of C2a-M48-SK1061 to reconstruct a highly revised phylogenetic tree with age estimates. We also performed the analysis of the geographical distribution and spatial autocorrelation of sub-branches. Dozens of new sub-branches were discovered, many sub-branches were nearly unique for Ewenki, Evens, Oroqen, Xibe, Manchu, Daur, and Mongolian. The topology of these unique sub-branches is the key evidence for understanding the complex evolutionary relationship between different Tungusic-speaking populations. The revised phylogeny provided a clear pattern for the differentiation history of haplogroup C2a-M48-SK1061 in the past 2,000 years. This study showed that the divergence pattern of founder lineage is essential to understanding the differentiation history of populations., Competing Interests: Author K-JL was employed by the company Chengdu 23Mofang Biotechnology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yu, Ao, Zhang, Liu, Wang, Meng, Li, Wei and Man.)

This study developed and implemented a driving power supply for light-emitting diode (LED) array streetlamps. The power stage was a quasi-resonant (QR)-flyback converter, its input power was the alternating-current power, and the LED array streetlamp was driven by the direct-current output power. The developed QR-flyback converter was operated in discontinuous conduction mode, and the pulse-width modulation (PWM) control chip was used to switch and conduct at the resonant valley of the drain-source voltage on the metal-oxide-semiconductor field-effect transistor (MOSFET) switch to reduce the switching loss. Moreover, the PWM control chip had a disable function, which was connected with a bright and extinguishable control circuit, and the high/low voltage level signal output by the Arduino development board can be used to control the output power of the QR-flyback converter, achieving bright and extinguishable controls for the LED array streetlamp.

Objectives: To study the differences in the clinical features of children with coronavirus disease 2019 (COVID-19) in different age groups during the epidemic of Omicron variant., Methods: A retrospective analysis was performed on the clinical data of 211 children with COVID-19 who were admitted to the Department of General Pediatrics, Zhongshan People's Hospital, from December 9, 2022 to January 8, 2023. According to their age, they were divided into 4 groups: 1 month-<1 year ( n =84), 1-<3 years group ( n =64), 3-<5 years ( n =29), and ≥5 years ( n =34). The above groups were compared in terms of general status, clinical features, ancillary examination results, treatment, and outcome., Results: The children aged <3 years accounted for 70.1% (148/211) of all hospitalized children with COVID-19, and the 3-<5 years group and the ≥5 years group had a significantly higher proportion of children with underlying diseases than the 1 month-<1 year group and the 1-<3 years group ( P <0.05). Compared with the other three groups, the 1 month-<1 year group had significantly higher incidence rates of dyspnea, nasal congestion/nasal discharge, diarrhea and significantly lower incidence rates of convulsion and nervous system involvement ( P <0.05). Moreover, compared with the other three groups, the 1 month-<1 year group had significantly higher incidence rates of increases in bile acid and creatine kinase isoenzyme and significantly lower incidence rates of decreased platelet count, increased neutrophil percentage, and decreased lymphocyte percentage ( P <0.05). The 1 month-<1 year group had a significantly higher incidence rate of mild COVID-19 than the 1-<3 years group and a significantly lower incidence rate of severe/critical COVID-19 than the other three groups ( P <0.05). Compared with the other three groups, the 1 month-<1 year group had a significantly higher proportion of children receiving oxygen inhalation therapy ( P <0.05)., Conclusions: Children with COVID-19 in different age groups have different clinical features during the epidemic of Omicron variant, especially between the children aged 1 month to <1 year and those aged ≥1 year.

Although it is widely recognized that the ancestors of Native Americans (NAs) primarily came from Siberia, the link between mitochondrial DNA (mtDNA) lineage D4h3a (typical of NAs) and D4h3b (found so far only in East China and Thailand) raises the possibility that the ancestral sources for early NAs were more variegated than hypothesized. Here, we analyze 216 contemporary (including 106 newly sequenced) D4h mitogenomes and 39 previously reported ancient D4h data. The results reveal two radiation events of D4h in northern coastal China, one during the Last Glacial Maximum and the other within the last deglaciation, which facilitated the dispersals of D4h sub-branches to different areas including the Americas and the Japanese archipelago. The coastal distributions of the NA (D4h3a) and Japanese lineages (D4h1a and D4h2), in combination with the Paleolithic archaeological similarities among Northern China, the Americas, and Japan, lend support to the coastal dispersal scenario of early NAs., Competing Interests: Declaration of interests The authors declare no competing interests. The authors from 23Mofang Biotechnology Co., Ltd, also declare no commercial or associative interests in connection with this work., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: It has been reported that twinfilin actin binding protein 1 (TWF1) is associated with the progression of breast and pancreatic cancers. However, the roles and mechanisms of TWF1 in lung adenocarcinoma (LUAD) have not been reported., Methods: The expression levels of TWF1 in LUAD and normal tissues were analyzed using The Cancer Genome Atlas (TCGA) database, and validation was carried out with 12 clinical samples. The relationship between TWF1 expression and LUAD patients' clinical indices and immunity was investigated. Cell Counting Kit-8 (CCK-8) and migration and invasion assays were employed to explore the effects of downregulated TWF1 on LUAD cell proliferation and metastasis., Results: TWF1 was upregulated in LUAD tissues, and upregulated TWF1 was correlated with the tumor (T) stage, node (N) stage, clinical classification, overall survival (OS), and progression-free interval (PFI) of LUAD patients. Moreover, the Cox regression analysis showed that TWF1 overexpression was an independent risk factor for the poor prognosis of LUAD patients. TWF1 expression was associated with tumor immune infiltration (such as dendritic cells resting, eosinophils, macrophages M0, and others), drug sensitivity (such as A-770041, Bleomycin, and BEZ235), tumor mutation burden (TMB), and sensitivity to immunotherapy. In the cell model, TWF1 expression interference significantly prohibited LUAD cell proliferation, migration, and invasion, which might be relevant to aberrant MMP1 protein downregulation., Conclusions: TWF1 overexpression was correlated with poor prognoses and immune status of LUAD patients. Inhibited TWF1 expression delayed the growth and migration of cancer cells by downregulating MMP protein, implying that TWF1 is a promising biomarker for the prognoses of LUAD patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-395/coif). The authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Purpose: To primarily investigate: (1) whether a 10-minute instant meditation practice using a mobile app could enhance arthroscopy performance and (2) whether a 10-day app-based meditation could reduce short-term arthroscopic skills deterioration., Methods: Orthopaedic residents with no previous experience in arthroscopy and meditation were randomly assigned to groups A, B, and C. After initial standard competency-based arthroscopy training on the simulator on day 1, a pretest was performed via the simulator by all participants to assess their initial level of performance, then groups A and B were required to practice app-based mindfulness meditation 10 min/day for 10 consecutive days while group C did nothing. On day 11, all participants returned to perform a posttest. Before the posttest, the participants in group A practiced app-based meditation (10 minutes), whereas groups B and C had no intervention., Results: In total, 43 participants were included and reached similar level of performance after initial training phase in day 1. On day 11, participants in group A had statistically a better instant arthroscopy performance than group B, with greater total score (mean difference [MD] 3.57; P < .001), less completion time (MD -42.89 seconds; P = .001), shorter camera (MD -23.38 cm; P < .001) and grasper (MD -15.23 cm; P = .002) path length, and less cartilage injury (MD -1.07%; P = .012). Participants in group B had less skills deterioration than group C, with better total score (MD -5.42; P < .001), less completion time (MD 51.96s; P = .002), camera path length (MD 28.41 cm; P = .007), and cartilage injury (MD 1.19%; P = .038)., Conclusions: Meditation training using a mobile app enhanced instant simulation-based arthroscopy performance and reduced short-term skills deterioration of orthopaedic residents with no arthroscopy hands-on experience., Clinical Relevance: A meditation using mobile app for clinicians and educators should be incorporated into simulation-based arthroscopy curriculums and perhaps clinical settings to improve arthroscopy performance and mental health of orthopaedic residents without any previous arthroscopy experience., (Copyright © 2022 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate the reliability and accuracy of deep learning technology in automatic sex estimation using the 3D reconstructed images of the computed tomography (CT) from the Chinese Han population., Methods: The pelvic CT images of 700 individuals (350 males and 350 females) of the Chinese Han population aged 20 to 85 years were collected and reconstructed into 3D virtual skeletal models. The feature region images of the medial aspect of the ischiopubic ramus (MIPR) were intercepted. The Inception v4 was adopted as the image recognition model, and two methods of initial learning and transfer learning were used for training. Eighty percent of the individuals' images were randomly selected as the training and validation dataset, and the remaining were used as the test dataset. The left and right sides of the MIPR images were trained separately and combinedly. Subsequently, the models' performance was evaluated by overall accuracy, female accuracy, male accuracy, etc., Results: When both sides of the MIPR images were trained separately with initial learning, the overall accuracy of the right model was 95.7%, the female accuracy and male accuracy were both 95.7%; the overall accuracy of the left model was 92.1%, the female accuracy was 88.6% and the male accuracy was 95.7%. When the left and right MIPR images were combined to train with initial learning, the overall accuracy of the model was 94.6%, the female accuracy was 92.1% and the male accuracy was 97.1%. When the left and right MIPR images were combined to train with transfer learning, the model achieved an overall accuracy of 95.7%, and the female and male accuracies were both 95.7%., Conclusions: The use of deep learning model of Inception v4 and transfer learning algorithm to construct a sex estimation model for pelvic MIPR images of Chinese Han population has high accuracy and well generalizability in human remains, which can effectively estimate the sex in adults.

Background: To investigate clinical manifestations and factors of perioperative brain injury (PBI) after surgical repair of coarctation of the aorta (CoA) combined with other heart malformations under cardiopulmonary bypass (CPB) in children under two years., Methods: The clinical data of 100 children undergoing CoA repair were retrospectively reviewed between January 2010 and September 2021. Univariate and multivariate analyses were performed to identify factors of PBI development. Hierarchical and K-means cluster analyses were conducted to evaluate the association between hemodynamic instability and PBI., Results: Eight children developed postoperative complications, and all of them had a favorable neurological outcome one year after surgery. Univariate analysis revealed eight risk factors associated with PBI. Multivariate analysis indicated operation duration (P = 0.04, odds ratio [OR], 2.93; 95% confidence interval [CI], 1.04 to 8.28) and pulse pressure (PP) minimum (P = 0.01; OR, 0.22; 95% CI, 0.06 to 0.76) were independently associated with PBI. The following three parameters emerged for cluster analysis: PP minimum, mean arterial pressure (MAP) dispersion, and systemic vascular resistance (SVR) average. Using cluster analysis, PBI mainly occurred in subgroups 1 (12%, three of 26) and 2 (10%, five of 48). The mean value of PP and MAP in subgroup 1 was significantly higher than in subgroup 2. The mean SVR in subgroup 1 was the highest. The lowest PP minimum, MAP, and SVR were observed in subgroup 2., Conclusion: Lower PP minimum and longer operation duration were independent risk factors for developing PBI in children under two years during CoA repair. Unstable hemodynamics should be avoided during CPB., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Previous studies of archaeology and history suggested that the rise and prosperity of Bronze Age culture in East Asia had made essential contribution to the formation of early state and civilization in this region. However, the impacts in perspective of genetics remain ambiguous. Previous genetic researches indicated the Y-chromosome Q1a1a-M120 and N1a2a-F1101 may be the two most important paternal lineages among the Bronze Age people in ancient northwest China. Here, we investigated the 9,000-years history of haplogroup N1a2a-F1101 with revised phylogenetic tree and spatial autocorrelation analysis. Materials and Methods: In this study, 229 sequences of N1a2a-F1101 were analyzed. We developed a highly-revised phylogenetic tree with age estimates for N1a2a-F1101. In addition, we also explored the geographical distribution of sub-lineages of N1a2a-F1101, and spatial autocorrelation analysis was conducted for each sub-branch. Results: The initial differentiation location of N1a2a-F1101 and its most closely related branch, N1a2b-P43, a major lineage of Uralic-speaking populations in northern Eurasia, is likely the west part of northeast China. After ~4 thousand years of bottleneck effect period, haplgroup N1a2a-F1101 experienced continuous expansion during the Chalcolithic age (~ 4.5 kya to 4 kya) and Bronze age (~ 4 kya to 2.5 kya) in northern China. Ancient DNA evidence supported that this haplogroup is the lineage of ruling family of Zhou Dynasty (~ 3 kya-2.2 kya) of ancient China. Discussion: In general, we proposed that the Bronze Age people in the border area between the eastern Eurasian steppe and northern China not only played a key role in promoting the early state and civilization of China, but also left significant traces in the gene pool of Chinese people., 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. The handling editor IY declared a past co-authorship with the author L-HW., (Copyright © 2023 Yu, Ao, Wang, Zhang, Sun, Li, Liu and Wei.)

Lung is the largest organ of the respiratory system. During hypoxia, pulmonary cells undergo rapid damage changes and activate the self-rescue pathways, thus leading to complex biomacromolecule modification. Death from mechanical asphyxia refers to death due to acute respiratory disorder caused by mechanical violence. Because of the absence of characteristic signs in corpse, the accurate identification of mechanical asphyxia has always been the difficulty in forensic pathology. This paper reviews the biomacromolecule changes under the pulmonary hypoxia condition and discusses the possibility of application of these changes to accurate identification of death from mechanical asphyxia, aiming to provide new ideas for related research.

Objective: This study aimed to explore the effects of tea polyphenols (TP) on inflammation of orbital fibroblasts in Graves' ophthalmopathy (GO) and to provide new ideas for GO treatment., Methods: Primary orbital fibroblasts were extracted from orbital adipose/connective tissues of patients with and without GO. Real-time quantitative PCR (RT-qPCR) was used to detect the expression of interleukin (IL)-6, IL-1β, and monocyte chemotactic protein (MCP)-1 in non-GO and GO orbital fibroblasts. The CCK-8 assay was used to determine the appropriate concentration of TP for subsequent experiments. RT-qPCR and enzyme-linked immunosorbent assay (ELISA) were performed to investigate the effects of TP on lipopolysaccharide (LPS)-induced production of inflammatory cytokines. Nuclear factor-κB (NF-κB) expression was measured using Western blotting analysis. NOD-like receptor 3 (NLRP3) expression was detected using both Western blotting analysis and immunofluorescence staining., Results: The mRNA levels of IL-6, IL-1β, and MCP-1 in GO orbital fibroblasts were significantly higher than those in non-GO cells. TP treatment significantly inhibited LPS-induced production of inflammatory factors, including IL-6, IL-1β, and MCP-1. TP also inhibited the expression levels of NF-κB and NLRP3. Inflammation in the GO orbital fibroblasts was higher than that in non-GO cells. TP inhibited the production of inflammatory cytokines in GO orbital fibroblasts in vitro through the NF-κB/NLRP3 pathway., Conclusion: These findings suggest that TP may have a potential role in GO treatment., (© 2023. The Author(s).)

Objective: The study aimed to examine the learning curve and short-term retention of arthroscopic skills acquired on a simulator., Design: Cohort study., Setting: Clinical Skills Training Center of Zhujiang Hospital of Southern Medical University PARTICIPANT AND METHODS: Orthopaedic residents (n = 14) without previous arthroscopy experience were included. After basic information was collected and an initial arthroscopy knowledge level test was administered, the subjects received standardised training on the simulator (day 1); then, they completed tasks on the simulator, including guided diagnostics (4 times), triangulation (5 times) and loose body removal (7 times). A learning curve for each skill was generated based on the total scores. The score of the last repetition of each task was the training level., Results: A total of 14 orthopedic residents were enrolled. All participants completed the training and testing. There was a learning curve over the course of training for all 3 arthroscopic skills (p < 0.001). On day 8 after the training, the mean score for guided diagnostics decreased from 49.9 to 48.9 (p = 0.001), and the retention rate was 97.8%. For triangulation, the mean total score decreased from 58.9 to 53.6 (p < 0.001), and the retention rate was 90.8%. For loose body removal, the mean total score decreased from 87.1 to 80.7 (p < 0.001), and the retention rate was 92.7%., Conclusions: Orthopaedic residents' arthroscopic skills learned through simulator training declined significantly in 1 week after the training, especially more difficult skills., (Copyright © 2022 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Multiple assessment tools are used in arthroscopic training and play an important role in feedback. However, it is not fully recognized as to the standard way to apply these tools. Our study aimed to investigate the use of assessment tools in arthroscopic training and determine whether there is an optimal way to apply various assessment tools in arthroscopic training., Methods: A search was performed using PubMed, Embase and Cochrane Library electronic databases for articles published in English from January 2000 to July 2021. Eligible for inclusion were primary research articles related to using assessment tools for the evaluation of arthroscopic skills and training environments. Studies that focussed only on therapeutic cases, did not report outcome measures of technical skills, or did not mention arthroscopic skills training were excluded., Results: A total of 28 studies were included for review. Multiple assessment tools were used in arthroscopic training. The most common objective metric was completion time, reported in 21 studies. Technical parameters based on simulator or external equipment, such as instrument path length, hand movement, visual parameters and injury, were also widely used. Subjective assessment tools included checklists and global rating scales (GRS). Among these, the most commonly used GRS was the Arthroscopic Surgical Skill Evaluation Tool (ASSET). Most of the studies combined objective metrics and subjective assessment scales in the evaluation of arthroscopic skill training., Conclusions: Overall, both subjective and objective assessment tools can be used as feedback for basic arthroscopic skill training, but there are still differences in the frequency of application in different contexts. Despite this, combined use of subjective and objective assessment tools can be applied to more situations and skills and can be the optimal way for assessment., Level of Evidence: Level III, systematic review of level I to III studies. Key messagesBoth subjective and objective assessment tools can be used as feedback for basic arthroscopic skill training.Combined use of subjective and objective assessment tools can be applied to more situations and skills and can be the optimal way for assessment.

Brain calcification is a critical aging-associated pathology and can cause multifaceted neurological symptoms. Cerebral phosphate homeostasis dysregulation, blood-brain barrier defects, and immune dysregulation have been implicated as major pathological processes in familial brain calcification (FBC). Here, we analyzed two brain calcification families and identified calcification co-segregated biallelic variants in the CMPK2 gene that disrupt mitochondrial functions. Transcriptome analysis of peripheral blood mononuclear cells (PBMCs) isolated from these patients showed impaired mitochondria-associated metabolism pathways. In situ hybridization and single-cell RNA sequencing revealed robust Cmpk2 expression in neurons and vascular endothelial cells (vECs), two cell types with high energy expenditure in the brain. The neurons in Cmpk2-knockout (KO) mice have fewer mitochondrial DNA copies, down-regulated mitochondrial proteins, reduced ATP production, and elevated intracellular inorganic phosphate (Pi) level, recapitulating the mitochondrial dysfunction observed in the PBMCs isolated from the FBC patients. Morphologically, the cristae architecture of the Cmpk2-KO murine neurons was also impaired. Notably, calcification developed in a progressive manner in the homozygous Cmpk2-KO mice thalamus region as well as in the Cmpk2-knock-in mice bearing the patient mutation, thus phenocopying the calcification pathology observed in the patients. Together, our study identifies biallelic variants of CMPK2 as novel genetic factors for FBC; and demonstrates how CMPK2 deficiency alters mitochondrial structures and functions, thereby highlighting the mitochondria dysregulation as a critical pathogenic mechanism underlying brain calcification., (© 2022. The Author(s).)

Background: Mortality and other clinical outcomes of culture-negative and culture-positive among patients with fungal sepsis have not been documented, and whether antifungal therapy prior to fungal culture reports is related to decreased mortality among patients remains largely controversial. This study aimed to determine the mortality and other clinical outcomes of patients with positive yeast cultures and further investigate the effects of initial empiric antifungal therapy., Methods: A retrospective study was conducted among septic patients using the Medical Information Mart for Intensive Care (MIMIC)-IV database. Patients with sepsis were divided into two groups based on first fungal culture status during intensive care unit (ICU) stay, and initial empirical antifungal therapy was prescribed based on physician's experience prior to fungal culture reports within 48 h. The primary outcome was in-hospital all-cause mortality. The secondary outcomes were 30-day all-cause mortality, 60-day all-cause mortality, length of ICU stay and length of hospital stay. Multivariate logistic regression, propensity score matching (PSM), subgroup analyses and survival curve analyses were performed., Results: This study included 18,496 sepsis patients, of whom 3,477 (18.8%) had positive yeast cultures. Patients with positive yeast cultures had higher in-hospital all-cause mortality, 60-day all-cause mortality, and longer lengths of ICU stay and hospital stay than those with negative yeast cultures after PSM (all p  < 0.01). Multivariate logistic regression analysis revealed that positive yeast culture was a risk factor for in-hospital mortality in the extended model. Subgroup analyses showed that the results were robust among the respiratory infection, urinary tract infection, gram-positive bacterial infection and bacteria-free culture subgroups. Interestingly, empiric antifungal therapy was not associated with lower in-hospital mortality among patients with positive yeast cultures, mainly manifested in stratification analysis, which showed that antifungal treatment did not improve outcomes in the bloodstream infection (odds ratio, OR 2.12, 95% CI : 1.16-3.91, p  = 0.015) or urinary tract infection groups ( OR 3.24, 95% CI : 1.48-7.11, p  = 0.003)., Conclusion: Culture positivity for yeast among sepsis patients was associated with worse clinical outcomes, and empiric antifungal therapy did not lower in-hospital all-cause mortality in the bloodstream infection or urinary tract infection groups in the ICU., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zou, Sun, Fu, Huang, Yang, Zhou, Ma, Zhu and Wu.)

Objective: Gouty arthritis (GA) is an inflammatory disease, and renal impairment may occur to varying degrees with the progress of disease. The neutrophil-to-lymphocyte ratio (NLR) is an inflammatory marker. In this study, we aimed to explore the association between NLR and renal impairment in GA., Materials and Methods: The subjects comprised 499 patients with gouty arthritis (GA) (473 men, 26 women; age range, 39-61 years old) from our hospital. They were divided into a chronic kidney disease (CKD) group (n = 206) and non-CKD group (n = 293) according to the glomerular filtration rate. Blood samples were collected during the gout flares. The differences in NLR, general data, and laboratory indexes of patients with GA between the two groups were compared, such as serum uric acid (SUA), serum creatinine (SCREA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), high-density lipoprotein (HDL), and low-density lipoprotein (LDL)., Results: NLR (3.38 vs. 2.38 (p < 0.001)) was higher in the CKD group, compared to the non-CKD group. Similarly, both SUA (527 vs. 507 (p < 0.05)) and SCREA (122 vs. 87 (p < 0.001)) were higher in the CKD group than in the non-CKD group. Multivariate logistic regression analysis showed that NLR (OR = 1.122, p < 0.05), age, hypertension, and SUA were risk factors for CKD in patients with GA, although HDL and HGB were protective factors. The receiver operating characteristic (ROC) curve analysis indicated that the area under the curve of NLR for predicting CKD in patients with GA was 0.646 (95% CI 0.597-0.694)., Conclusion: Our data showed that NLR might be an important potential factor for evaluating renal impairment in GA during flares., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

The viral envelope is essential for virus maturation. Virus-mediated syncytium formations are induced by viral envelope proteins that cause membrane fusion of the infected cells. Polydnaviridae (Polydnavirus) are enveloped viruses with multiple nucleocapsids, and virions mature in symbiotic parasitoid wasp ovaries. However, the mechanism governing the envelope packaging of multiple nucleocapsids remains unclear. In this study, we used transmission electron microscopy to examine the process whereby multiple nucleocapsids of Microplitis bicoloratus bracovirus are packaged into an envelope and observed envelope-fusion-syncytium formation in symbiotic wasp calyx cells during virus maturation. The virus maturation process in calyx cells comprised four stages: pre-virogenic stroma, virogenic stroma, assembly, and fusion. Each virus contained a single envelope with one nucleocapsid in the assembly stage; multiple envelopes then fused to form a viral envelope with multiple nucleocapsids (i.e., the envelope-fusion-syncytium) around the envelope fusion core in the fusion stage. The envelope-fusion-syncytium then stabilized the virions that were released into the lumen of the ovary across the calyx epithelial layer. The phagocytic calyx epithelial cells on the border of the calyx and ovary lumen cleared the majority of non-enveloped nucleocapsids. In contrast, non-phagocytic calyx epithelial cells with microvilli and a cuticular line between the ovary wall and the lumen remained intact in the ovary lumen. These results indicate that envelope-fusion-syncytium formation is important for packaging multiple nucleocapsids in bracovirus maturation.

Alongside sustainable development as a major global aim, the contribution made by globalization to environmental issues has become crucial in recent decades. Prior studies have focused on how trade in globalization influences the environment. However, multiple economic, social, and political factors are also important, the integration of which needs to be considered in sustainable development. Sharp and smooth breaks in time series models are the consequence of real-world structures. Using the bootstrap autoregressive-distributed lag test with a Fourier function, the present study reexamined the nexus between globalization and the environment in China, the United States, and India. The empirical results indicate that in the United States, the nexus between globalization and the environment is cointegrated in the long-term. In the short term, globalization is improving the environment in the United States and India. However, in China, globalization is resulting in environmental degradation. This research will assist policymakers in developing comprehensive strategies for sustainable development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wu, Chang, Wu, Leng, Lin and Huang.)

Bioactivity-guided fraction of an extract of Sophora flavescens to identify antibacterial compounds against Acinetobacter baumannii , led to the isolation of two new compounds, (2″ R )-5-methoxy-7-hydroxy-8-lavandulylchromone (13) and (2 S , βS )-(-)-sophobiflavonoid CE (19), and 18 known flavonoids, (6a R ,11a R )-(-)-maackiain (1), (2 S )-(-)-8-prenylnaringenin (2), (2 S )-(-)-exiguaflavanone K (3), (2 S )-(-)-sophoraflavanone G (4), (2 S )-(-)-leachianone A (5), (2 S )-(-)-kushenol E (6), (2 S )-(-)-leachianone G (7), (±)-kushenol F (8), (2 S )-(-)-kurarinone (9), (2 S )-(-)-kurarinol (10), (2  R ,3 R )- (+)-3,7,4'-trihydroxy-5-methoxy-8-prenylflavanone (11), (2 S )-(-)-isoxanthohumol (12), (2 S )-(-)-2'-methoxykurarinone (14), (2  R ,3 R )-(+)-kushenol I (15), calycosin (16), kuraridin (17), (2 S )-(-)-kushenol A (18), and trifolirhizin (20). Their structures were elucidated based on NMR, MS, and CD spectroscopic analysis. Among them, 1 , 2 , 5 , and 15 exerted modest antibacterial activity against A. baumannii , with MIC 95 of 128-256 μg/mL for 2 and 256-512 μg/mL for 1 , 5 and 15 .

Hemichannels (HCs)/gap junctions (GJs) and immunoglobulin (Ig)-like domain-containing proteins (IGLDCPs) are involved in the innate-adaptive immune response independently. Despite of available evidence demonstrating the importance of HCs/GJs and IGLDCPs in initiating, implementing, and terminating the entire immune response, our understanding of their mutual interactions in immunological function remains rudimentary. IGLDCPs include immune checkpoint molecules of the immunoglobulin family expressed in T and B lymphocytes, most of which are cluster of differentiation (CD) antigens. They also constitute the principal components of the immunological synapse (IS), which is formed on the cell surface, including the phagocytic synapse, T cell synapse, B cell synapse, and astrocytes-neuronal synapse. During the three stages of the immune response, namely innate immunity, innate-adaptive immunity, and adaptive immunity, HCs/GJs and IGLDCPs are cross-activated during the entire process. The present review summarizes the current understanding of HC-released immune signaling factors that influence IGLDCPs in regulating innate-adaptive immunity. ATP-induced "eat me" signals released by HCs, as well as CD31, CD47, and CD46 "don't eat me" signaling molecules, trigger initiation of innate immunity, which serves to regulate phagocytosis. Additionally, HC-mediated trogocytosis promotes antigen presentation and amplification. Importantly, HC-mediated CD4 + T lymphocyte activation is critical in the transition of the innate immune response to adaptive immunity. HCs also mediate non-specific transcytosis of antibodies produced by mature B lymphocytes, for instance, IgA transcytosis in ovarian cancer cells, which triggers innate immunity. Further understanding of the interplay between HCs/GJs and IGLDCPs would aid in identifying therapeutic targets that regulate the HC-Ig-like domain immune response, thereby providing a viable treatment strategy for immunological diseases. The present review delineates the clinical immunology-related applications of HC-Ig-like domain cross-activation, which would greatly benefit medical professionals and immunological researchers alike. HCs/GJs and IGLDCPs mediate phagocytosis via ATP; "eat me and don't eat me" signals trigger innate immunity; HC-mediated trogocytosis promotes antigen presentation and amplification in innate-adaptive immunity; HCs also mediate non-specific transcytosis of antibodies produced by mature B lymphocytes in adaptive immunity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Meng, Chen, Ahmadian, Zan, Luo and Jiang.)

Objectives: To retrospectively analyze homicide cases of death after injection and provide reference for forensic identification., Methods: Six homicide cases of death after injection which were investigated by the Criminal Investigation Team of Shanghai Public Security Bureau were collected and analyzed, including case situation, scene investigation, autopsy and other materials., Results: The 6 cases were premeditated crimes, 5 cases took place in private spaces, and 5 cases involved the victims approached by suspects' decoy. There were no obvious abnormalities at the scene of the 6 cases. In 6 cases, the victim's body surface injury was mild or no, lividity color was abnormal, and the needlestick injury showed different manifestations from conventional medical measures., Conclusions: Death after injection is a highly concealed crime and easy to be ignored. For the suspected injection injury found in autopsy, it is necessary to carefully examine, identify and analyze, be alert to the situation of injecting poison (drug) and do a good job in evidence fixation and material extraction.

Individual identification is one of the research hotspots in the practice of forensic science, and the judgment is usually built on the comparison of the unique biological characteristics of the individual, such as fingerprints, iris and DNA. With the dramatic increase in the number of cases related to video image investigations, there is an increasing need for the technology to identify individuals based on the macroscopic comparison of facial appearance biometrics. At present, with the introduction of computer three-dimensional (3D) modeling and 3D superimposition comparison technology, considerable progress has been made in individual identification methods based on macroscopic comparison of facial appearance biometrics. This paper reviews individual facial appearance biometric methods based on macroscopical comparison, comprehensively analyzes the advantages and limitations of different methods, and puts forward recommendations and prospects for subsequent research.

The excessive deposition of extracellular matrix (ECM) is the main characteristic of liver fibrosis, and hepatic stellate cells (HSCs) are the main source of ECM. The removal of activated HSCs has a reversal effect on liver fibrosis. Western blot and MTT analysis indicated that curcumol could relieve hepatic fibrosis by promoting HSCs receptor-interacting protein kinase 1/3 (RIP1/RIP3)-dependent necroptosis. Importantly, autophagy flow was monitored by constructing the mRFP-GFP-LC3 plasmid, and it was found that curcumol cleared activated HSCs in a necroptosis manner that was dependent on autophagy. Our study suggested that the activation of necrosome formed by RIP1 and RIP3 depended on Atg5, and that autophagosomes were also necessary for curcumol-induced necroptosis. Furthermore, microscale thermophoresis and co-immunoprecipitation assay results proved that curcumol could target Sirt1 to regulate autophagy by reducing the acetylation level of Atg5. The HSCs-specific silencing of Sirt1 exacerbated CCl 4 -induced liver fibrosis in mice. The deacetylation of Atg5 not only accelerated the accumulation of autophagosomes but also enhanced the interaction between Atg5 and RIP1/RIP3 to induce necroptosis. Overall, our study indicated that curcumol could activate Sirt1 to promote Atg5 deacetylation and enhanced its protein-protein interaction function, thereby inducing autophagy and promoting the necroptosis of HSCs to reduce liver fibrosis., (© 2022 John Wiley & Sons Ltd.)

A typical characteristics of polydnavirus (PDV) infection is a persistent immunosuppression, governed by the viral integration and expression of virulence genes. Recently, activation of caspase-3 by Microplitis bicoloratus bracovirus (MbBV) to cleave Innexins, gap junction proteins, has been highlighted, further promoting apoptotic cell disassembly and apoptotic body (AB) formation. However, whether ABs play a role in immune suppression remains to be determined. Herein, we show that ABs transmitted immunosuppressive signaling, causing recipient cells to undergo apoptosis and dismigration. Furthermore, the insertion of viral-host integrated motif sites damaged the host genome, stimulating eIF5A nucleocytoplasmic transport and activating the eIF5A-hypusination translation pathway. This pathway specifically translates apoptosis-related host proteins, such as P53, CypA, CypD, and CypJ, to drive cellular apoptosis owing to broken dsDNA. Furthermore, translated viral proteins, such Vank86, 92, and 101, known to complex with transcription factor Dip3, positively regulated DHYS and DOHH transcription maintaining the activation of the eIF5A-hypusination. Mechanistically, MbBV-mediated extracellular vesicles contained inserted viral fragments that re-integrated into recipients, potentially via the homologous recombinant repair system. Meanwhile, this stimulation regulated activated caspase-3 levels via PI3K/AKT 308 and 473 dephosphorylation to promote apoptosis of granulocyte-like recipients Sf9 cell; maintaining PI3K/AKT 473 phosphorylation and 308 dephosphorylation inhibited caspase-3 activation leading to dismigration of plasmatocyte-like recipient High Five cells. Together, our results suggest that integration-mediated eIF5A hypusination drives extracellular vesicles for continuous immunosuppression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Chen, Cai, Yan, Peng, Li, Cui, Han, Zhang, Meng, Tang, Cai, Long and Luo.)

In this work, we report on the synthesis of InSe nanobelts through a catalyst-free chemical vapor deposition (CVD) growth approach. A remarkable blue shift of the peak photoresponse was observed when the thickness of the InSe nanobelt decreases from 562 to 165 nm. Silvaco Technology Computer Aided Design (TCAD) simulation reveals that such a shift in spectral response should be ascribed to the wavelength-dependent absorption coefficient of InSe, for which incident light with shorter wavelengths will be absorbed near the surface, while light with longer wavelengths will have a greater penetration depth, leading to a red shift of the absorption edge for thicker nanobelt devices. Considering the above theory, three kinds of photodetectors sensitive to blue (450 nm), green (530 nm), and red (660 nm) incident light were achieved by tailoring the thickness of the nanobelts, which can enable the spectral reconstruction of a purple "H" pattern, suggesting the potential application of 2D layered semiconductors in full-color imaging.

A visible-light-promoted atomic substitution reaction for transforming thiocacids into carboxylic acids with dimethyl sulfoxide (DMSO) as the oxygen source has been developed, affording various alkyl and aryl carboxylic acids in over 90% yields. The atomic substitution process proceeds smoothly through the photochemical reactivity of the formed hydrogen-bonding adduct between thioacids and DMSO. A DMSO-involved proton-coupled electron transfer (PCET) and the simultaneous generation of thiyl and hydroxyl radicals are proposed to be key steps for realizing the transformation.

Objective: To compare the result of the artificial intelligence (AI) recognition-based fluorescence method and that of traditional flow cytometry in the examination of the sperm DNA fragmentation index (DFI) and assess the reliability of the AI-based fluorescence detection., Methods: Using flow cytometry and the AI-based fluorescence method, we examined the sperm DFI in the semen samples collected from 338 outpatients. We analyzed the correlation between the results and compared the positive rates detected by the two methods. We repeated the AI-based fluorescence method twice for each semen sample to observe its technical stability in the detection of sperm DFI., Results: The result of flow cytometry was well correlated with that of the AI-based fluorescence method in the detection of sperm DFI (R2 = 0.7131), but poorly correlated for low-concentration, sticky semen and some other extreme samples (R2 = 0.2065). No statistically significant difference was found between the two methods in the positive rate of detection. The AI-based fluorescence method exhibited an excellent technical stability (R2 = 0.9671)., Conclusion: The AI-based fluorescence method has an excellent technical stability in the detection of sperm DFI and the result is not significantly different from that of traditional flow cytometry.

Diatom test is the main laboratory test method in the diagnosis of drowning in forensic medicine. It plays an important role in differentiating the antemortem drowning from the postmortem drowning and inferring drowning site. Artificial intelligence (AI) automatic diatom test is a technological innovation in forensic drowning diagnosis which is based on morphological characteristics of diatom, the application of AI algorithm to automatic identification and classification of diatom in tissues and organs. This paper discusses the morphological diatom test methods and reviews the research progress of automatic diatom recognition and classification involving AI algorithms. AI deep learning algorithm can assist diatom testing to obtain objective, accurate, and efficient qualitative and quantitative analysis results, which is expected to become a new direction of diatom testing research in the drowning of forensic medicine in the future.

Objectives: To retrospectively analyze diatom test cases of corpses in water and discuss the value of quantitative analysis of diatoms in the diagnosis of drowning., Methods: A total of 490 cases of water-related death were collected. They were divided into drowning group and postmortem immersion group according to the cause of death. Diatoms in lung, liver, kidney tissue and water sample were analyzed quantitatively by microwave digestion-vacuum filtration-automated scanning electron microscopy (MD-VF-Auto SEM) method. The ratios of content of diatoms in lung tissue and water sample ( C L / C D ) were calculated., Results: The results of diatom test for three organs (lung, liver and kidney) were all positive in 400 cases (85.5%); the content of diatom in lung, liver, kidney tissues, and water samples of drowning group were (113 235.9±317 868.1), (26.7±75.6), (23.3±52.2) and (12 113.3±21 760.0) cells/10 g, respectively; the species of diatom were (7.5±2.8), (2.6±1.9), (2.9±2.1) and (8.9±3.0) types, respectively; the C L / C D of drowning group and postmortem immersion group were (100.6±830.7) and (0.3±0.4), respectively., Conclusions: Quantitative analysis of diatoms can provide supportive evidence for the diagnosis of drowning, and the parameter C L / C D can be introduced into the analysis to make a more accurate diagnosis of drowning.

Background: Triple negative breast cancer (TNBC) is a highly heterogeneous breast cancer subtype with a poor prognosis due to its extremely aggressive nature and lack of effective treatment options. This study aims to summarize the current hotspots of TNBC research and evaluate the TNBC research trends, both qualitatively and quantitatively., Methods: Scientific publications of TNBC-related studies from January 1, 2010 to October 17, 2020 were obtained from the Web of Science database. The BICOMB software was used to obtain the high-frequency keywords layout. The gCLUTO was used to produce a biclustering analysis on the binary matrix of word-paper. The co-occurrence and collaboration analysis between authors, countries, institutions, and keywords were performed by VOSviewer software. Keyword burst detection was performed by CiteSpace., Results: A total of 12,429 articles related to TNBC were identified. During 2010-2020, the most productive country/region and institution in TNBC field was the USA and The University of Texas MD Anderson Cancer Center, respectively. Cancer Research, Journal of Clinical Oncology, and Annals of Oncology were the first three periodicals with maximum publications in TNBC research. Eight research hotspots of TNBC were identified by co-word analysis. In the core hotspots, research on neoadjuvant chemotherapy, paclitaxel therapy, and molecular typing of TNBC is relatively mature. Research on immunotherapy and PARP inhibitor for TNBC is not yet mature but is the current focus of this field. Burst detection of keywords showed that studies on TNBC proteins and receptors, immunotherapy, target, and tumor cell migration showed bursts in recent three years., Conclusion: The current study revealed that TNBC studies are growing. Attention should be paid to the latest hotspots, such as immunotherapy, PARP inhibitors, target, and TNBC proteins and receptors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hao, Jia, Dai, Huo, Zhang, Liu and Wang.)

Objective: Previous studies have shown that increased neutrophils, as a manifestation of oxidative stress, may be involved in the progression of kidney disease. To our knowledge, little is known about the relationship between neutrophils and renal impairment in rheumatoid arthritis (RA). Therefore, we aim to investigate whether neutrophil is associated with renal impairment in RA patients., Methods: We retrospectively investigated the renal function of 602 RA patients in the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine by estimated glomerular filtration rate (eGFR) from September 2018 and September 2019. The exposure variable was neutrophils, and the main outcome was eGFR. General data (gender, age, duration, hypertension, diabetes, hobbies, and medication history), whole blood markers, lipid indexes, and inflammatory indexes were collected as much as possible. We used multivariable logistic regression analysis to evaluate the association between neutrophils and renal impairment in RA participants., Results: A total of 89 cases (14.8%) had renal impairment with eGFR < 60 ml/min/1.73 m 2 , and 75 cases (84.3%) were female. Subgroup analysis showed that female (odds ratio [OR] = 0.523, 95% confidence interval [CI]: 0.318-0.867, p = .011), neutrophils greater thsn 7.5 × 10 9 /L (OR = 2.314, 95% CI: 1.310-4.087, p = .004), NLR > 3.53 (OR = 1.757, 95% CI: 1.104-2.799, p = .018), hemoglobin less than 120 g/L (OR = 2.413, 95% CI: 1.418-4.118, p = .001), and UA > 360 μmol/L (OR = 6.052, 95% CI: 3.708-9.878, p < .001) was related to renal damage in RA. Adjusted for several confounders, the multivariable analysis indicated that neutrophils greater than 7.5 × 10 9 /L (OR = 1.784, 95% CI: 1.164-3.288, p = .031) was independently associated with an increased risk of renal impairment in RA., Conclusion: Our study demonstrated that neutrophils greater than 7.5 × 10 9 /L was associated with a high risk of renal impairment in RA, suggesting that neutrophil may be a biomarker for renal impairment in RA., (© 2021 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Objective: The purpose of this hospital clinic based study was to evaluate the potential risk factors associated with the prevalence of MetS in RA population., Methods: From January 2015 to October 2018, 717 patients with RA and 717 healthy controls who were treated or performed physical examination in Tianjin First Central Hospital were enrolled in this study. The basic disease diagnoses were recorded. A questionnaire was performed on all participants to assess the demographic details of the RA cohort. Moreover, laboratory indicators related to glucose and lipid metabolism in patients with RA were also detected. The potential risk factors for MetS were also analyzed., Results: The prevalence of MetS were 31.2% and 34.2% in case and control groups, respectively (P = .22). There were lower levels of HDL-C, obesity, TG, LDL-C and TC in case group than control group (all P < .05). The hypertension levels in healthy controls was decreased in compared with patients with RA (P < .05). Nevertheless, in patients with RA, complement 3 (OR: 1.02; 95% CI: 1.01-1.03, P = .007) and less glucocorticoids use (OR: 0.63, 95% CI: 0.39-0.99, P = .046) were associated with MetS., Conclusion: The prevalence of MetS was not associated with RA. Complement 3 may be associated with the higher prevalence of MetS in patients with RA. Glucocorticoids treatment may be associated with MetS., (© 2021 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Plant cell and water relationship regulates morphological, physiological and biochemical characteristics to optimize carboxylation for enhanced biomass yield in sugarcane. Insufficient water irrigation is one of the serious problems to impair potential yield of agriculturally important sugarcane cash crop by loss in plant performance. Our study aims to reveal consequences of foliar spray of silicon (Si) using calcium metasilicate powder (Wollastonite, CaO.SiO 2 ) to alleviate the adverse effects of limited water irrigation in sugarcane. Silicon (0, 50, 100 and 500 ppm) was applied as foliar spray on normally grown 45 days old sugarcane plants. Further, these plants were raised at half field capacity (50%) using water irrigation precisely up to 90 days under open environmental variables. Consequently, restricted irrigation impaired plant growth-development, leaf relative water content (%), photosynthetic pigments, SPAD unit, photosynthetic performance, chlorophyll fluorescence variable yield (Fv/Fm) and biomass yield. Notably, it has enhanced values of proline, hydrogen peroxide (H 2 O 2 ), malondialdehyde (MDA), antioxidative defense enzyme molecules viz., catalase (CAT), ascorbate peroxidase (APx) and superoxide dismutase (SOD). The foliar spray of Si defended sugarcane plants from limited water irrigation stress as Si quenched harmful effect of water-deficit and also enhanced the operation of antioxidant defense machinery for improved sugarcane plant performance suitably favored stomatal dynamics for photosynthesis and plant productivity., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)