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Abstract Salmonella enterica, a prominent foodborne pathogen, contributes significantly to global foodborne illnesses annually. This species exhibits significant genetic diversity, potentially impacting its infectivity, disease severity, and antimicrobial resistance. Whole genome sequencing (WGS) offers comprehensive genetic insights that can be utilized for virulence assessment. However, existing bioinformatic tools for studying Salmonella virulence have notable limitations. To address this gap, a Salmonella Virulence Database with a non-redundant, comprehensive list of putative virulence factors was constructed. Two bioinformatic analysis tools, Virulence Factor Profile Assessment and Virulence Factor Profile Comparison tools, were developed. The former provides data on similarity to the reference genes, e-value, and bite score, while the latter assesses the presence/absence of virulence genes in Salmonella isolates and facilitates comparison of virulence profiles across multiple sequences. To validate the database and associated bioinformatic tools, WGS data from 43,853 Salmonella isolates spanning 14 serovars was extracted from GenBank, and WGS data previously generated in our lab was used. Overall, the Salmonella Virulence database and our bioinformatic tools effectively facilitated virulence assessment, enhancing our understanding of virulence profiles among Salmonella isolates and serovars. The public availability of these resources will empower researchers to assess Salmonella virulence comprehensively, which could inform strategies for pathogen control and risk evaluations associated with human illnesses.

Abstract Background Plant fungal diseases present a major challenge to global agricultural production. Despite extensive efforts to develop fungicides, particularly succinate dehydrogenase inhibitors (SDHIs), their effectiveness is often limited by poor retention of fungicide droplets on hydrophobic leaves. The off-target losses and unintended release cause fungal resistance and severe environmental pollution. Results To update the structure of existing SDHIs and synchronously realize the efficient utilization, we have employed a sophisticated supramolecular strategy to optimize a structurally novel SDH inhibitor (AoH25), creating an innovative supramolecular SDH fungicide (AoH25@β-CD), driven by the host-guest recognition principle between AoH25 and β-cyclodextrin (β-CD). Intriguingly, AoH25@β-CD self-assembles into biocompatible supramolecular nanovesicles, which reinforce the droplet/foliage (liquid-solid) interface interaction and the effective wetting and retention on leaf surfaces, setting the foundation for enhancing fungicide utilization. Mechanistic studies revealed that AoH25@β-CD exhibited significantly higher inhibition of SDH (IC50 = 1.56 µM) compared to fluopyram (IC50 = 244.41 µM) and AoH25 alone (IC50 = 2.29 µM). Additionally, AoH25@β-CD increased the permeability of cell membranes in Botryosphaeria dothidea, facilitating better penetration of active ingredients into pathogenic cells. Further experimental outcomes confirmed that AoH25@β-CD was 88.5% effective against kiwifruit soft rot at a low-dose of 100 µg mL-1, outperforming commercial fungicides such as fluopyram (52.4%) and azoxystrobin (65.4%). Moreover, AoH25@β-CD showed broad-spectrum bioactivity against oilseed rape sclerotinia, achieving an efficacy of 87.2%, outstripping those of fluopyram (48.7%) and azoxystrobin (76.7%). Conclusion This innovative approach addresses key challenges related to fungicide deposition and resistance, improving the bioavailability of agricultural chemicals. The findings highlight AoH25@β-CD as a novel supramolecular SDH inhibitor, demonstrating its potential as an efficient and sustainable solution for plant disease management. Graphical Abstract

This study investigated the effects of replacing flour with different proportions of mulberry fruit powder on the quality and antioxidant properties of steamed bread, with the goal of preparing steamed bread with high nutritional value and expanding the utilization of mulberries. The impact of varying amounts of mulberry powder on the color difference, texture, microstructure, and antioxidant effects of fermented dough and steamed bread was measured, and the correlation between dough characteristics and steamed bread quality was also analyzed. The results showed that as the amount of mulberry fruit powder increased, the dough's elasticity, L* value (lightness), b* value (yellowness), and w value (whiteness) significantly decreased, while the a* value (redness) increased. Changes in gluten protein structure led to a significant decrease in the specific volume of mulberry steamed bread and an increase in hardness, resulting in a decline in steamed bread quality. The moisture content, elasticity, and chewiness of the steamed bread initially increased and then decreased. Correlation analysis between the dough and steamed bread results revealed significant (P

Abstract The WHO recently published a Tobacco Knowledge Summary (TKS) synthesizing current evidence on tobacco and COPD, aiming to raise awareness among a broad audience of health care professionals. Furthermore, it can be used as an advocacy tool in the fight for tobacco control and prevention of tobacco-related disease. This article builds on the evidence presented in the TKS, with a greater level of detail intended for a lung-specialist audience. Pulmonologists have a vital role to play in advocating for the health of their patients and the wider population by sharing five key messages: (1) Smoking is the leading cause of COPD in high-income countries, contributing to approximately 70% of cases. Quitting tobacco is an essential step toward better lung health. (2) People with COPD face a significantly higher risk of developing lung cancer. Smoking cessation is a powerful measure to reduce cancer risk. (3) Cardiovascular disease, lung cancer and type-2 diabetes are common comorbidities in people with COPD. Quitting smoking not only improves COPD management, but also reduces the risk of developing these coexisting conditions. (4) Tobacco smoke also significantly impacts children’s lung growth and development, increasing the risk of respiratory infections, asthma and up to ten other conditions, and COPD later in life. Governments should implement effective tobacco control measures to protect vulnerable populations. (5) The tobacco industry’s aggressive strategies in the marketing of nicotine delivery systems and all tobacco products specifically target children, adolescents, and young adults. Protecting our youth from these harmful tactics is a top priority.

Bladder diverticulum cancer is a malignant tumor growing in the bladder diverticulum. Its incidence rate is low, and it is common in elderly men. The main clinical symptom is painless gross hematuria. Bladder diverticulum cancer often occurs in acquired bladder diverticula and is more prone to infiltrating the surrounding area than other bladder tumors. In this article, we report a case of bladder diverticulum cancer clinically manifested as a mass in the lower left abdomen with gross hematuria. CT and MR examinations showed a mass on the left side of the pelvic cavity, locally connected to the bladder wall, and suspected to originate from the bladder. Surgery and pathology confirmed the diagnosis as bladder diverticulum cancer. Enhanced CT and MR are the recommended non-invasive imaging examinations for bladder diverticulum cancer that help clarify its location and tumor staging. CT urography has a great value in differential diagnosis. In this article, we aimed to summarize the clinical manifestations, imaging features, differential diagnosis, and treatment methods of bladder diverticulum cancer to improve our understanding of the disease and help make accurate diagnosis through imaging examination.

Abstract Collecting duct carcinoma (CDC) is an aggressive rare subtype of kidney cancer with unmet clinical needs. Little is known about its underlying molecular alterations and etiology, primarily due to its rarity, and lack of preclinical models. This study aims to comprehensively characterize molecular alterations in CDC and identify its therapeutic vulnerabilities. Through whole-exome and transcriptome sequencing, we identified KRAS hotspot mutations (G12A/D/V) in 3/13 (23%) of the patients, in addition to known TP53, NF2 mutations. 3/13 (23%) patients carried a mutational signature (SBS22) caused by aristolochic acid (AA) exposures, known to be more prevalent in Asia, highlighting a geologically specific disease etiology. We further discovered that cell cycle-related pathways were the most predominantly dysregulated pathways. Our drug screening with our newly established CDC preclinical models identified a CDK9 inhibitor LDC000067 that specifically inhibited CDC tumor growth and prolonged survival. Our study not only improved our understanding of oncogenic molecular alterations of Asian CDC, but also identified cell-cycle machinery as a therapeutic vulnerability, laying the foundation for clinical trials to treat patients with such aggressive cancer.

Abstract Type I CRISPR-Cas systems are widespread and have exhibited high versatility and efficiency in genome editing and gene regulation in prokaryotes. However, due to the multi-subunit composition and large size, their application in eukaryotes has not been thoroughly investigated. Here, we demonstrate that the type I-F2 Cascade, the most compact among type I systems, with a total gene size smaller than that of SpCas9, can be developed for transcriptional activation in human cells. The efficiency of the engineered I-F2 tool can match or surpass that of dCas9. Additionally, we create a base editor using the I-F2 Cascade, which induces a considerably wide editing window (~30 nt) with a bimodal distribution. It can expand targetable sites, which is useful for disrupting functional sequences and genetic screening. This research underscores the application of compact type I systems in eukaryotes, particularly in the development of a base editor with a wide editing window.

Abstract Background Ubiquitin-specific protease 15 (USP15) exhibits amplifications in various tumors, including gastric cancer (GC), yet its biological function and mechanisms in GC progression remain elusive. Methods Here, we established stable USP15 knockdown or overexpression GC cell lines and explored the potential mechanism of USP15 in GC. Besides, we also identified interacting targets of USP15. Results USP15 knockdown significantly impeded cell proliferation, invasion, epithelial-mesenchymal transition, and distal colonization in xenograft models, while enhancing oxaliplatin's antitumor effect. USP15 was involved in ubiquitination modification of glycolytic regulators. Silencing of USP15 suppressed glycolytic activity and impaired mitochondrial functions. Interference with USP15 expression reversed tumor progression and distal colonization in vivo. HKDC1 and IGF2BP3 were found as core interacting targets of USP15, and HKDC1 was identified as a substrate for ubiquitination modification by USP15, whereby USP15 regulated glucose metabolism activity by inhibiting the ubiquitination degradation of HKDC1. Conclusions Our study unveiled aberrantly high expression of USP15 in GC tissues, correlating with malignant progression and nonresponse to neoadjuvant therapy. USP15 inhibitors, if developed, could be effective in promoting chemotherapy through glucose metabolism remodeling.

Abstract Background Gap tension is an important factor influencing the clinical outcomes of total knee arthroplasty (TKA). Traditional mechanical alignment (MA) places importance on neutral alignment and often requires additional soft tissue releases, which may be related to patient dissatisfaction. Conversely, the functional alignment requires less soft tissue release to achieve gap balance. Conventional gap tension instruments present several shortcomings in practice. The aim of this study is to introduce a new gap balancing technique with FA using the modified spacer-based gap tool and the MAKO robotic arm system. Methods A total of 22 consecutive patients underwent primary TKA using the MAKO robotic arm system. The gap tension was assessed and adjusted with the modified spacer-based gap tool during the operation. Patient satisfaction was evaluated post-operatively with a 5-point Likert scale. Clinical outcomes including lower limb alignment, Knee Society Score (KSS) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) were recorded before surgery, 3 months and 1 year after surgery. Results The range of motion (ROM) was significantly increased (p

Abstract Background Breast and cervical cancer are the most common cancers in women, and are associated with high morbidity and mortality rates. Cancer screening can facilitate early diagnosis, reduce mortality, and ease the burden of cancer. Social support and self-efficacy are strongly associated with cancer screening behavior. The present study aimed to explore the mediating effect of self-efficacy on social support and cancer screening behavior. Methods In this cross-sectional survey study conducted from June to October 2023, 312 women aged 35–65 years were recruited from the East Coast area of China. A general information questionnaire, cancer screening behavior questionnaire, social support scale and self-efficacy scale were used to collect data. Descriptive statistics were used to analyze the general characteristics of participants; one-way analysis of variance was used to test for differences in the measured variables; and Pearson’s correlation analyses were used to describe the relationship among social support, self-efficacy, and cancer screening behavior. A mediation model was constructed and analyzed using the PROCESS macro for SPSS. Results The mean (standard deviation) screening behavior score for breast cancer and cervical cancer was 3.98 (2.79), representing an intermediate level. Self-efficacy was closely related to social support and cancer screening behavior. Social support showed a significant positive correlation with self-efficacy (r = 0.37, p

Abstract Background Salidroside is the major bioactive and pharmacological active substance in Rhodiola rosea L. It has been reported to have neuroprotective effects on cerebral ischemia/reperfusion (I/R). However, whether salidroside can enhance neural regeneration after cerebral I/R is still unknown. This study investigated the effects of salidroside on the endogenous neural regeneration after cerebral I/R and the related mechanism. Methods Focal cerebral I/R was induced in rats by transient middle cerebral artery occlusion/reperfusion (MCAO/R). The rats were intraperitoneally treated salidroside once daily for 7 consecutive days. Neurobehavioral assessments were performed at 3 days and 7 days after the injury. TTC staining was performed to assess cerebral infarct volume. To evaluate the survival of neurons, immunohistochemical staining of Neuronal Nuclei (NeuN) in the ischemic hemisphere were conducted. Also, immunofluorescence double or triple staining of the biomarkers of proliferating neural progenitor cells in Subventricular Zone (SVZ) and striatum of the ischemia hemisphere were performed to investigate the neurogenesis. Furthermore, reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression of neurotrophic factors (NTFs) brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Expression of Notch1 and its target molecular Hes1 were also analyzed by western-blotting and RT-PCR. Results Salidroside treatment ameliorated I/R induced neurobehavioral impairment, and reduced infarct volume. Salidroside also restored NeuN positive cells loss after I/R injury. Cerebral I/R injury significantly increased the expression of 5-Bromo-2’-Deoxyuridine (BrdU) and doublecotin (DCX), elevated the number of BrdU/Nestin/DCX triple-labeled cells in SVZ, and BrdU/Nestin/glial fibrillary acidic protein (GFAP) triple-labeled cells in striatum. Salidroside treatment further promoted the proliferation of BrdU/DCX labeled neuroblasts and BrdU/Nestin/GFAP labeled reactive astrocytes. Furthermore, salidroside elevated the mRNA expression and protein concentration of BDNF and NGF in ischemia periphery area, as well. Mechanistically, salidroside elevated Notch1/Hes1 mRNA expression in SVZ. The protein levels of them were also increased after salidroside administration. Conclusions Salidroside enhances the endogenous neural regeneration after cerebral I/R. The mechanism of the effect may involve the regulation of BDNF/NGF and Notch signaling pathway.

The issue of non-fragile sampled-data control for synchronizing Markov jump Lur'e systems (MJLSs) with time-variant delay was investigated. The time-variant delay allowed for uncertainty that was constrained to an interval with defined upper and lower boundaries. The components of the nonlinear function within the MJLSs were considered to satisfy either Lipschitz continuity or non-decreasing monotonicity. Numerically tractable conditions that ensured stochastic synchronization with a predefined $ \mathcal{L}_{2}-\mathcal{L}_{\infty} $ disturbance attenuation level for the drive-response MJLSs were established, utilizing time-dependent two-sided loop Lyapunov-Krasovskii functionals, together with integral and matrix inequalities. An exact mathematical expression of the desired controller gains can be obtained based on these conditions. Finally, an example with numerical simulation was employed to demonstrate the effectiveness of the proposed control strategies.

Objectives: Through the reflection of young breast cancer women on their selves and identities, we explored expectations of the wife role that they need to fulfill to return to their families, aimed to provide a reference basis for medical professionals to develop interventions related to cancer family rehabilitation. Methods: Descriptive phenomenological methods and purposive sampling were used. Young breast cancer patients and their spouses were selected for semi-structured face-to-face interviews in the study from March to April 2023 at the department of breast surgery and oncology center of a Class A tertiary hospital in Xuzhou City, China. The interviews were transcribed verbatim and analyzed using Colaizzi’s phenomenological approach. Results: Twenty patients and six spouses were interviewed. The mean patient age was (35.95 ± 3.36) years, and the mean spouse was (37.67 ± 5.28) years. Young breast cancer patients were concerned about three main wife expectations during their treatment and rehabilitation: preserving self-love and self-esteem (paying attention to physical health, embracing the disease, and regaining confidence in female characters); adjustment of conjugal relationships (harmonious and effective couple communication, providing support for marriage and love, and creating a beautiful married life together); assisting in family recovery (relieving stress on spouses from caregiving and finances, and management of daily household chores). Conclusions: The wife role expectations of young breast cancer women and their spouses encompass three core aspects: self, couple, and family. Self-esteem and self-love are the most fundamental expectations of the wife role, while adjusting the couple’s relationship and assistance in family rehabilitation represent higher expectations. This study can help healthcare professionals and cancer families gain a more comprehensive understanding of the wife role expectations for young cancer women, thereby enabling the development of couple-centered interventions to promote patient recovery and enhance the resilience of marriages and families.

Abstract Accumulating evidence implicates that herpes simplex virus type 1 (HSV-1) has been linked to the development and progression of Alzheimer’s disease (AD). HSV-1 infection induces β-amyloid (Aβ) deposition in vitro and in vivo, but the effect and precise mechanism remain elusive. Here, we show that HSV-1 infection of the brains of transgenic 5xFAD mice resulted in accelerated Aβ deposition, gliosis, and cognitive dysfunction. We demonstrate that HSV-1 infection induced the recruitment of microglia to the viral core to trigger microglial phagocytosis of HSV-GFP-positive neuronal cells. In addition, we reveal that the NLRP3 inflammasome pathway induced by HSV-1 infection played a crucial role in Aβ deposition and the progression of AD caused by HSV-1 infection. Blockade of the NLRP3 inflammasome signaling reduces Aβ deposition and alleviates cognitive decline in 5xFAD mice after HSV-1 infection. Our findings support the notion that HSV-1 infection is a key factor in the etiology of AD, demonstrating that NLRP3 inflammasome activation functions in the interface of HSV-1 infection and Aβ deposition in AD.

Abstract Mucus injury associated with goblet cell (GC) depletion constitutes an early event in inflammatory bowel disease (IBD). Using single-cell sequencing to detect critical events in mucus dysfunction, we discover that the Kazal-type serine protease inhibitor SPINK4 is dynamically regulated in colitic intestine in parallel with disease activities. Under chemically induced colitic conditions, the grim status in Spink4-conditional knockout mice is successfully rescued by recombinant murine SPINK4. Notably, its therapeutic potential is synergistic with existing TNF-α inhibitor infliximab in colitis treatment. Mechanistically, SPINK4 promotes GC differentiation using a Kazal-like motif to modulate EGFR-Wnt/β-catenin and -Hippo pathways. Microbiota-derived diacylated lipoprotein Pam2CSK4 triggers SPINK4 production. We also show that monitoring SPINK4 in circulation is a reliable noninvasive technique to distinguish IBD patients from healthy controls and assess disease activity. Thus, SPINK4 serves as a serologic biomarker of IBD and has therapeutic potential for colitis via intrinsic EGFR activation in intestinal homeostasis.

Objective Accurate differentiation within the LI-RADS category M (LR-M) between hepatocellular carcinoma (HCC) and non-HCC malignancies (mainly intrahepatic cholangiocarcinoma [CCA] and combined hepatocellular and cholangiocarcinoma [cHCC-CCA]) is an area of active investigation. We aimed to use radiomics-based machine learning classification strategy for differentiating HCC from CCA and cHCC-CCA on contrast-enhanced ultrasound (CEUS) images in high-risk patients with LR-M nodules.

Introduction The rapid growth of e-cigarette usage among youth and young people has emerged as a significant public health concern. It is imperative to initiate effective vaping prevention campaigns and undertake relevant research to address this pressing issue. This research seeks to identify effective video advertisements to deter young people from starting to use e-cigarettes. It aims to offer evidencebased insights and recommendations for creating communication materials and designing messages for youth e-cigarette prevention efforts. Methods College students aged 18–24 years (n=40) participated in focus groups within this qualitative study. After viewing four stimulus videos, participants discussed what they perceived as effective and ineffective video characteristics, as well as suggestions for future videos. Results Effective video characteristics included the use of real-life testimonials, displaying specific health hazards, revealing harmful chemical ingredients and the deceptive nature of flavors, and positively perceived effectiveness. Participants generally found that videos with strong visual impact and graphics were more engaging and that approaches using fear and emotion were more effective. Ineffective characteristics included complex and exaggerated information, lack of empathy and irrelevance, insufficiently specific information, extreme and death-themed content, industry messages, as well as preachy tones, animations, metaphors, dull formats, excessive length, and scenes of e-cigarette use. Conclusions Developing anti-e-cigarette campaign materials for youth necessitates target audience-focused qualitative research. This helps in deeply exploring and identifying effective themes and messages, as well as video characteristics and details while avoiding ineffective or even misleading messages and themes from young people’s perspectives outside the United States. Future development of e-cigarette prevention videos for Chinese college students may consider incorporating localized real-life testimonial cases to convey specific harms, including self-efficacy information, and utilizing fear and emotional appeals.

Tumor microenvironments (TMEs) have received increasing attention in recent years as they play pivotal roles in tumorigenesis, progression, metastases, and resistance to the traditional modalities of cancer therapy like chemotherapy. With the rapid development of nanotechnology, effective antineoplastic nanotherapeutics targeting the aberrant hallmarks of TMEs have been proposed. The appropriate design and fabrication endow nanomedicines with the abilities for active targeting, TMEs-responsiveness, and optimization of physicochemical properties of tumors, thereby overcoming transport barriers and significantly improving antineoplastic therapeutic benefits. This review begins with the origins and characteristics of TMEs and discusses the latest strategies for modulating the TMEs by focusing on the regulation of biochemical microenvironments, such as tumor acidosis, hypoxia, and dysregulated metabolism. Finally, this review summarizes the challenges in the development of smart anti-cancer nanotherapeutics for TME modulation and examines the promising strategies for combination therapies with traditional treatments for further clinical translation.

Abstract Polyploid is considered an advantage that has evolved to be more environmentally adaptable than its diploid. To understand if doubled chromosome of diploid rice can improve drought tolerance, we evaluated the diploid (2X) and autotetraploid (4X) plants of three indica and three japonica varieties. Drought stress in the plastic bucket of four-leaf stage revealed that the drought tolerance of 4X plants was lower than that of its diploid donor plants. The assay of photosynthetic rate of all varieties showed that all 4X varieties had lower rates than their diploid donors. The capacity for reactive oxygen species production and scavenging varied among different 2X and 4X varieties. Further, transcriptomic analysis of 2X and 4X plants of four varieties under normal and drought condition showed that the wide variation of gene expression was caused by difference of varieties, not by chromosome ploidy. However, weighted gene co-expression network analysis (WGCNA) revealed that the severe interference of photosynthesis-related genes in tetraploid plants under drought stress is the primary reason for the decrease of drought tolerance in autotetraploid lines. Consistently, new transcripts analysis in autotetraploid revealed that the gene transcription related with mitochondrion and plastid of cell component was influenced most significantly. The results indicated that chromosome doubling of diploid rice weakened their drought tolerance, primarily due to disorder of photosynthesis-related genes in tetraploid plants under drought stress. Maintain tetraploid drought tolerance through chromosome doubling breeding in rice needs to start with the selection of parental varieties and more efforts.

Abstract Background To discuss the current status of reproductive concerns and its correlation with fear of recurrence and level of family support in patients of childbearing age with gynecologic malignancies. Methods A convenient sampling method was used to enroll 188 patients with gynecologic malignancies in Nanjing Maternity and Child Health Care Hospital, Nanjing Drum Tower Hospital, General Hospital of Ningxia Medical University, and Haian Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine from September 2022 to April 2023. Patients were assessed using general information questionnaire, Reproductive Concerns After Cancer Scale (RCAC), Fear of Cancer Recurrence Inventory (FCRI) questionnaire, and Perceived Social Support-Family (PSS-FA) Scale. Results Among patients of childbearing age with gynecologic malignancies, the total RCAC score was (54.35 ± 7.52), indicating a moderate level of reproductive concerns. Patients scored (20.98 ± 4.51) on FCRI, implying a moderate level of fear of recurrence. The PSS-FA score was (9.57 ± 2.76), denoting a moderate level of family support. The total score and each dimensional score of RCAC were positively correlated with FCRI total score (P

Abstract Background Migraine, as a prevalent neurologic disorder, involves intricate and yet incompletely elucidated pathophysiological mechanisms. A plethora of research findings underscores the pivotal role played by astrocytes in the progression of migraines. In order to elucidate the current advances and directions in research pertaining to astrocytes in migraines, we conducted bibliometric analysis of relevant literature and visualized the results. Subsequently, we expound upon these findings to contribute to the evolving understanding of the role of astrocytes in migraine pathophysiology. Methods On November 21, 2023, we conducted a search on Web of Science (WOS), restricting the document type to articles or reviews and language to English. Following a meticulous selection process involving three researchers, we identified the literature to be included in our analysis. Subsequently, we employed Microsoft Office Excel programs, R, VOSviewer, Scimago Graphica, and CiteSpace software to conduct visualization analysis of basic information and trends regarding journals, countries/regions, and influential authors, institutions, keywords, and papers. Results As of November 21, 2023, relevant literature has been published in 71 journals across 27 countries/regions. This corpus comprises contributions from 576 authors affiliated with 220 institutions, encompassing 865 keywords and referencing 6065 scholarly articles. CEPHALALGIA stands out as the most influential journal in this field, while authors PIETROBON D and DALKARA T have significant impact. The United States is highly influential, with CNR and UNIV PADUA emerging as highly influential institutions. The predominant category is Neurosciences. Conclusions Future investigators may continue to focus on migraines with aura, familial hemiplegic migraine (FHM), and the crucial calcitonin gene-related peptide (CGRP) system. Employing advanced observational techniques, such as imaging, researchers should pay attention to cellular and tissue structures, such as microglia and the trigeminal ganglion, as well as mechanisms involving inflammation and central sensitization. Moreover, animal models are paramount in obtaining high-quality evidence.

Objective: To investigate the role and the molecular mechanisms of apoptotic signaling in ferroptosis to regulate tumor radiosensitivity. Methods: Reactive oxygen species (ROS) and lipid peroxide levels were detected in Mouse embryonic fibroblasts(MEFs) with Bcl-xL or Mcl-1 deficiency induced by erastin. Colony formation, ROS, lipid peroxidation and the transcription/translation levels of PTGS2 were measured in Bcl-xL knockdown tumor cells induced by 5 ​Gy γ-rays or co-treated with ferrostatin-1 (Ferr-1). The protein levels of LPCAT3, ACSL4 and PEBP1 in Bcl-xL knockout MEF cells were evaluated in Bcl-xL knockout MEF cells post-radiation. Moreover, the interaction of heat shock protein 90 (HSP90) with Bcl-xL, GPX4, or LAMP2A was detected by protein mass spectrometry and immunoprecipitation assays. Results: Manipulating Bcl-xL levels facilitated radiation-induced ferroptosis by augmenting the enzymatic oxidation of polyunsaturated fatty acids (PUFAs) and enhancing chaperone-mediated autophagy (CMA) of glutathione peroxidase 4 (GPX4) (MEF cell line: t=4.540, P＜0.01; A549 ​cell line: t=56.16, P＜0.0001; t=4.885, P＜0.01; HCT116 ​cell line: t=14.75, P＜0.01; t=7.363, P＜0.05). Downregulating Bcl-xL expression promoted the activity of acyl-CoA synthetase long-chain family member 4 (ACSL4), thus increasing the enzymatic oxidation of PUFAs (t=4.258, P＜0.01). Moreover, depletion of Bcl-xL expedited the CMA process targeting GPX4 by facilitating the association of GPX4 with heat shock protein 90 (HSP90) and LAMP2A following radiation exposure. Subsequent degradation of GPX4 led to the accumulation of lipid peroxides, ultimately triggering ferroptosis. Conclusions: Our study provides initial insights into the regulatory role of Bcl-xL in ferroptosis and underscores the potential of targeting Bcl-xL as a promising therapeutic strategy for cancer by modulating both apoptotic and ferroptotic pathways.

Abstract Objective To evaluate the feasibility, safety and efficacy of concurrent simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) combined with nimotuzumab in the treatment of locally advanced esophageal squamous cell cancer (ESCC). Methods Eligible patients were histologically proven to have locally advanced ESCC, and were unable to tolerate or refuse concurrent chemoradiotherapy (CCRT). Enrolled patients underwent concurrent SIB-IMRT in combination with nimotuzumab. SIB-IMRT: For the planning target volume of clinical target volume (PTV-C), the prescription dose was 50.4 Gy/28fractions, 1.8 Gy/fraction, 5fractions/week, concurrently, the planning target volume of gross tumor (PTV-G) undergone an integrated boost therapy, with a prescription dose of 63 Gy/28fractions, 2.25 Gy/fraction, 5 fractions/week. Nimotuzumab was administered concurrently with radiotherapy, 200 mg/time, on D1, 8, 15, 22, 29, and 36, with a total accumulation of 1200 mg through intravenous infusion. The primary endpoint of the study was the safety and efficacy of the combined treatment regimen, and the secondary endpoints were 1-year, 2-year, and 3-year local control and survival outcomes. Results (1) From December 2018 to August 2021, 35 patients with stage II-IVA ESCC were enrolled and 34 patients completed the full course of radiotherapy and the intravenous infusion of full-dose nimotuzumab. The overall completion rate of the protocol was 97.1%. (2) No grade 4–5 adverse events occurred in the entire group. The most common treatment-related toxicity was acute radiation esophagitis, with a total incidence of 68.6% (24/35). The incidence of grade 2 and 3 acute esophagitis was 25.7% (9/35) and 17.1% (6/35), respectively. The incidence of acute radiation pneumonitis was 8.6% (3/35), including one case each of Grades 1, 2, and 3 pneumonitis. Adverse events in other systems included decreased blood cells, hypoalbuminemia, electrolyte disturbances, and skin rash. Among these patients, five experienced grade 3 electrolyte disturbances during the treatment period (three with grade 3 hyponatremia and two with grade 3 hypokalemia). (3) Efficacy: The overall CR rate was 22.8%, PR rate was 71.4%, ORR rate was 94.2%, and DCR rate was 97.1%.(4) Local control and survival: The 1-, 2-, and 3-year local control (LC) rate, progression-free survival(PFS) rate, and overall survival(OS) rate for the entire group were 85.5%, 75.4%, and 64.9%; 65.7%, 54.1%, and 49.6%; and 77.1%, 62.9%, and 54.5%, respectively. Conclusions The combination of SIB-IMRT and nimotuzumab for locally advanced esophageal cancer demonstrated good feasibility, safety and efficacy. It offered potential benefits in local control and survival. Acute radiation esophagitis was the primary treatment-related toxicity, which is clinically manageable. This comprehensive treatment approach is worthy of further clinical exploration (ChiCTR1900027936).

Objective Thoracic spinal epidural abscess (SEA) is a rare but dangerous condition, and traditional surgical methods are accompanied by extensive trauma and approach‐related complications. Here we introduce the technique of full‐endoscopic transforaminal debridement and decompression and evaluate its feasibility for treating brucellar thoracic SEA. Methods We performed thoracic full‐endoscopic transforaminal decompression and debridement on two patients with neurological deficits caused by brucellar SEA, which is mainly composed of granulation tissue rather than pus. Postoperative MRI was conducted to confirm the presence of any residual abscess compressing the nerves. Frankel grading was employed to assess the recovery of neurological function, and complications were documented. Results There were no occurrences of dural tear, postoperative hematoma, or pulmonary complications. Their neurological function had significantly improved after surgery, and postoperative MRI confirmed no residual abscess compressing the spinal cord. During the 2‐year follow‐up, one patient achieved complete recovery (from Frankel‐C to Frankel‐E), while another patient improved from Frankel‐A to Frankel‐D. Neither patient experienced infection recurrence, instability, nor kyphotic deformity. Conclusion We described the novel application of transforaminal endoscopic surgery in brucellar thoracic granulomatous SEA and preliminarily indicated the feasibility of this technique as a minimally invasive alternative to open surgery.

Histone deacetylases (HDACs) are proteases that play a key role in chromosome structural modification and gene expression regulation, and the involvement of HDACs in cancer, the nervous system, and the metabolic and immune system has been well reviewed. Our understanding of the function of HDACs in the vascular system has recently progressed, and a significant variety of HDAC inhibitors have been shown to be effective in the treatment of vascular diseases. However, few reviews have focused on the role of HDACs in the vascular system. In this study, the role of HDACs in the regulation of the vascular system mainly involving endothelial cells and vascular smooth muscle cells was discussed based on recent updates, and the role of HDACs in different vascular pathogenesis was summarized as well. Furthermore, the therapeutic effects and prospects of HDAC inhibitors were also addressed in this review.

Abstract MXene‐based Zn‐ion capacitors (ZICs) with adsorption‐type and battery‐type electrodes demonstrate high energy storage and anti‐self‐discharge capabilities, potentially being paired with triboelectric nanogenerators (TENGs) to construct self‐powered systems. Nevertheless, inadequate interlayer spacing, deficient active sites, and compact self‐restacking of MXene flakes pose hurdles for MXene‐based ZICs, limiting their applications. Herein, black phosphorus (BP)‐Zn‐MXene hybrid is formulated for MXene‐based ZIC via a two‐step molecular engineering strategy of Zn‐ion pre‐intercalation and BP nanosheet assembly. Zn ions as intercalators induce cross‐linking of MXene flakes with expandable interlayer spacing to serve as scaffolds for BP nanosheets, thereby providing sufficient accessible active sites and efficient migration routes for enhanced Zn‐ion storage. The density functional theory calculations affirm that zinc adsorption and diffusion kinetics are significantly improved in the hybrid. A wearable ZIC with the hybrid delivers a competitive areal energy of 426.3 µWh cm−2 and ultra‐low self‐discharge rate of 7.0 mV h−1, achieving remarkable electrochemical matching with TENGs in terms of low energy loss, matched capacity, and fast Zn‐ion storage. The resultant self‐powered system efficiently collects and stores energy from human motion to power microelectronics. This work advances the Zn‐ion storage of MXene‐based ZICs and their synergy with TENG in self‐powered systems.

Abstract The commercial utilization of Zn metal anodes with high plating capacity is significantly hindered by the uncontrolled growth of dendrites and associated side reactions. Herein, a robust artificial ion‐sieving MXene flake (MXF)‐coating layer, with abundant polar terminated groups, is constructed to regulate the interfacial Zn2+ deposition behavior. In particular, the fragmented MXF coupled with in situ generated quantum dots not only has strong Zn affinity to homogenize electric fields but also generates numerous zincophilic sites to reduce nucleation energy, thus securing a uniform dendrite‐free surface. Additionally, the porous coating layer with polar groups allows the downward diffusion of Zn2+ to achieve bottom‐up deposition and repels the excessive free water and anions to prevent parasitic reactions. The ion‐sieving effect of MXF is firmly verified in symmetric cells with high areal capacity of 10–40 mAh cm−2 (1.0 mA cm−2) and depth of discharge of 15%–60%. Therefore, the functional MXF‐coated anode manifests long‐term cycling with 2700 h of stable plating/stripping in Zn||Zn cell. Such rational design of MXF protective layer breaks new ground in developing high plating capacity zinc anodes for practical applications.

Abstract During the past few decades, pyroelectric sensors have attracted extensive attention due to their prominent features. However, their effectiveness is hindered by low electric output. In this study, the laser processed lithium niobate (LPLN) wafers are fabricated to improve the temperature–voltage response. These processed wafers are utilized to construct pyroelectric sensors as well as human–machine interfaces. The laser induces escape of oxygen and the formation of oxygen vacancies, which enhance the charge transport capability on the surface of lithium niobate (LN). Therefore, the electrodes gather an increased quantity of charges, increasing the pyroelectric voltage on the LPLN wafers to a 1.3 times higher voltage than that of LN wafers. For the human–machine interfaces, tactile information in various modes can be recognized by a sensor array and the temperature warning system operates well. Therefore, the laser modification approach is promising to enhance the performance of pyroelectric devices for applications in human–machine interfaces.

ObjectiveThis study explores the benefits of targeted-immunotherapy combination in third-line or beyond treatment for microsatellite stable (MSS) metastatic colorectal cancer (mCRC) in a real-world setting.MethodsPatients with MSS mCRC who were treated with either a targeted-immunotherapy combination or targeted therapy alone in the third-line or beyond setting at our hospital from August 2018 to August 2022 were included in the study. Inclusion criteria comprised patients treated with targeted therapy alone or in combination with immunotherapy. Effectiveness was compared between treatments, and patients with the potential to benefit from targeted-immunotherapy combination were identified.ResultsAmong 71 patients, 31 received targeted therapies alone (TT group) and 40 received a combination of targeted therapy and immunotherapy (TI group). The TI group had higher objective response rates (20% vs 3.2%) and disease control rates (82.5% vs 58.1%). The median progression-free survival was significantly better in the TI group (4.6 vs 4.1 months, P = 0.027). Liver metastasis was associated with poor prognosis, while patients with only lung metastases had the longest median progression-free survival of 12.3 months with combination therapy.ConclusionThe study indicates that targeted-immunotherapy combination offers more benefits than targeted therapy alone for MSS mCRC in the third-line or beyond setting.

The study of specific physiological processes from the perspective of network physiology has gained recent attention. Modeling the global information integration among the separated functionalized modules in structural and functional brain networks is a central problem. In this article, the preferentially cutting–rewiring operation (PCRO) is introduced to approximatively describe the above physiological process, which consists of the cutting procedure and the rewiring procedure with specific preferential constraints. By applying the PCRO on the classical Erdös–Rényi random network (ERRN), three types of isolated nodes are generated, based on which the common leaves (CLs) are formed between the two hubs. This makes the initially homogeneous ERRN experience drastic changes and become heterogeneous. Importantly, a statistical analysis method is proposed to theoretically analyze the statistical properties of an ERRN with a PCRO. Specifically, the probability distributions of these three types of isolated nodes are derived, based on which the probability distribution of the CLs can be obtained easily. Furthermore, the validity and universality of our statistical analysis method have been confirmed in numerical experiments. Our contributions may shed light on a new perspective in the interdisciplinary field of complexity science and biological science and would be of great and general interest to network physiology.