Association of Systemic Inflammatory Response Index and Neutrophil-to-lymphocyte Ratio on Unfavorable Functional Outcomes in Acute Ischemic Stroke Patients after Endovascular Therapy.

BACKGROUND: Inflammatory markers for the prognosis of acute ischemic stroke (AIS) with endovascular therapy remain unclear. The purpose of this study was to investigate the association between the Systemic Inflammatory Response Index (SIRI) and Neutrophil-to-Lymphocyte Ratio (NLR) with unfavorable functional outcomes at 90-day in individuals of AIS who underwent endovascular therapy. METHODS: 128 AIS patients who had endovascular therapy were enrolled from the Nanjing Stroke Registry between September 2019 and November 2022. Peripheral venous blood was collected from patients within 24 h of admission for information on the following parameters: neutrophil count, lymphocyte count, monocyte count. Then, the SIRI and NLR values were calculated, and the association among SIRI, NLR, and modified Rankin Scale (mRS) scores 90 days after endovascular therapy was examined via univariate and multivariate logistic analyses. ROC curves were utilized to determine the best threshold for SIRI and NLR in predicting negative neurological outcomes following endovascular treatment for patients with AIS. RESULTS: 128 participants were evaluated, among which 50% had unfavorable outcomes. Linear regression analysis showed that the best threshold for SIRI was >1.407 (OR = 1.265; 95% CI, 1.071-1.493; P = 0.006), and for NLR it was >5.347 (odds ratio; OR = 1.088; 95% confidence interval [CI], 1.007-1.175; P = 0.033). These results revealed NLR and SIRI as significant predictors of unfavorable outcomes at 90 days. The AUC for SIRI and NLR in predicting 90-day adverse outcomes was 0.643 and 0.609, respectively. CONCLUSIONS: Higher SIRI and NLR levels at admission may lead to unfavorable outcomes at 90 days for AIS patients with endovascular therapy.

Personal Norms Predict Defending in Bullying: Mediating Role of Anticipated Pride and Guilt.

Recent studies have shown that bystander intervention involves moral engagement. However, the underlying internal mechanism is still poorly understood. Drawing on the norm activation model (NAM), Study 1 (questionnaire; n = 502) and Study 2 (experiment; n = 144) were conducted to investigate the influence of personal norms on defending through the mediating factors of anticipated pride and anticipated guilt. After controlling for age and gender, Study 1 revealed a significant positive association between personal norms and defending. This relationship was mediated by both anticipated pride and guilt, highlighting their parallel roles in explaining the influence of personal norms on defending. Study 2 investigated using writing tasks to manipulate personal norms from participants. The results revealed that the priming group had significantly higher levels of anticipated pride, guilt, and defending than the control group. Study 2 replicated the results of Study 1 in testing the mediated path, enhancing the reliability of research findings. This study expands the scope of the application of NAM by examining the interplay between personal norms, anticipated pride, anticipated guilt, and defending, as well as exploring the implications of these findings for interventions against bullying. Moral education should focus not only on the responsibility and obligation of bystanders to intervene in bullying incidents but also on the need to assist students in forming a moral compass within themselves that guides them to defend victims through moral emotions actively.

The Roles of RNA N6-methyladenosine Modifications in Systemic Lupus Erythematosus.

N6-methyladenosine (m6A) modification is the most widespread RNA internal modification involved in RNA metabolism. M6A regulators consist of writers, erasers and readers. They exert their function by methylation, demethylation and recognization respectively, participating in cell biology and immune responses. Previously, the focus of m6A modification is its effect on tumor progress. Currently, extensive m6A-related studies have been performed in autoimmune diseases, such as RA, IBD and SLE, revealing that the unique influence of m6A modification in autoimmunity is undeniable. In this review, we summarize the function of m6A regulators, analyze their roles in pathogenic immune cells, summarize the m6A modification in SLE, and provide the potential m6A-targeting therapies for autoimmune diseases.

Acute and long COVID-19 symptoms and associated factors in the omicron-dominant period: a nationwide survey via the online platform Wenjuanxing in China.

BACKGROUNDS: To our knowledge, there is no available nationwide data on omicron symptom patterns in China mainland. We aim to determine the acute and long COVID-19 symptoms in the omicron-dominant period and to evaluate its association with risk factors. METHODS: We designed a cross-sectional nationwide study and data about self-reported symptoms were collected by an online platform named Wenjuanxing. Eligible participants were aged 25-65 years and were symptomatic. In this study, the ratios of the number of people of different ages and genders were weighted by the data from the Seventh National Census (2020 years), and validated by a published nationwide representative study through comparing smoking rates. Descriptive indicators were calculated for demographic characteristics, diagnosis ways, and duration time, acute symptoms, hospitalization, severity and long COVID-19 symptoms. And, the associations between risk factors and acute and long COVID-19 symptoms were analyzed by multivariable logistic regression models. RESULTS: A total of 32,528 individuals diagnosed as COVID-19 infection from October 1, 2022 to February 21, 2023 were included. The first three acute symptoms of COVID-19 infection were fever (69.90%), headache (62.63%), and sore throat (54.29%), respectively. The hospitalization rate within 7 days was 3.07% and symptoms disappearance rate within 21 days was 68.84%, respectively. Among 3983 COVID-19 patients with 3 months or more time difference between first infection and participation into the study, the long COVID-19 rate was 19.68% and the primary symptoms were muscle weakness (19.39%), headache (17.98%) and smell/taste disorder (15.18%). Age groups, smoking, marriage status and vaccination were risk factors for numbers of acute phase symptoms and long COVID-19 symptoms. Lastly, female and current smokers also showed more numbers of symptoms during acute infection period. CONCLUSIONS: In Chinese mainland, our respondent indicated that current smokers and women were associated with acute COVID-19 symptoms, which should be treated with caution due to the lack of representative.

Exploration of ETV6::ABL1-positive AML with concurrent NPM1 and FLT3-ITD mutations.

ETV6::ABL1 is a rare fusion gene that found in MPN, ALL, and AML. It has a complex and diverse formation mechanism due to the reciprocal orientations of the ETV6 and ABL1 genes relative to the centromeres. NPM1 is frequently mutated in adult AML, often accompanied by FLT3-ITD, which suggests molecular synergisms in AML pathogenesis. Previous reports on ETV6::ABL1 mostly focus on FLT3-ITD. In this study, we present a case of AML with ETV6::ABL1, along with NPM1 and FLT3-ITD. The patient showed a rapid increase in primitive cells at the initial stage, along with the presence of immature granulocytes and erythrocytes. Through cytogenetic analysis, fluorescence in situ hybridization (FISH), and RNA-seq, we elucidated the mechanism behind the formation of the ETV6::ABL1 fusion gene. Despite conventional chemotherapy failure and rapid tumor proliferation, we attempted to add FLT3 inhibitor sorafenib to the treatment, along with chemotherapy bridging to haploidentical transplantation. After haplo-HSCT, a combination of sorafenib and dasatinib was administered as maintenance therapy. The patient achieved complete remission (CR) and maintained it for 11 months. The intricate genetic landscape observed in this case presents diagnostic dilemmas and therapeutic challenges, emphasizing the importance of a comprehensive understanding of its implications for disease classification, risk stratification, and treatment selection.

Effectiveness of acupuncture in treating patients with pain and mental health concerns: the results of the Alberta Complementary Health Integration Project.

Background: This study presents real-world evidence on the clinical outcomes of the Alberta Complementary Health Integration Project (ABCHIP), which utilized acupuncture to address pain and mental health issues in two vulnerable populations in Alberta: youth (aged 24 and below) and elderly (aged 55 and above). Methods: Over 282 days, a total of 606 patients received 5,424 acupuncture treatments. Tailored to each patients' specific pain and mental health concerns, an individualized treatment plan was selected, following a standard treatment protocol lasting 1 to 3 months. Patients were evaluated at least twice: initially and upon completing therapy. Primary treatment outcomes were assessed using various measures, including the Brief Pain Inventory (BPI), Pittsburgh Sleep Quality Index (PSQI), Patient Health Questionnaire 9 (PHQ9), PROMIS Anxiety 8a and its pediatric form PROMIS Anxiety-Pediatric, PROMIS Short Form v1.0 Fatigue 8a and its pediatric counterpart PROMIS Pediatric Short Form v2.0 Fatigue 10a, PROMIS Short Form v1.1 Anger 5a and its version PROMIS SF v2.0 5a, and EQ-5D-5L. These measures gauged pain reduction, improved sleep quality, reduced depression, anxiety, fatigue, anger, and quality of life, respectively. Results: Analysis of data from 500 patients who received at least 6 acupuncture sessions through ABCHIP showed statistically significant improvements in clinical outcomes. Among this group, the subgroup of 235 patients who received at least 12 sessions demonstrated the most favorable treatment outcomes, including an 75.5% reduction in pain severity, a 53.1% improvement in sleep quality, a 78.4% drop in depression, a 41.1% decline in anxiety, a 43.7% decrease in fatigue, a 38.2% decrease in anger, and a 42.6% improvement in overall quality of life. Conclusion: Integrating acupuncture with usual care demonstrates promise in enhancing mental health, alleviating chronic and general pain, and improving overall quality of life. The findings suggest that integrative programs, such as ABCHIP, present an effective approach to addressing pain and mental health concerns in vulnerable populations, providing valuable insights for future healthcare interventions.

Reversal of injury-associated retinal ganglion cell gene expression by a phosphodiesterase anchoring disruptor peptide.

Loss of retinal ganglion cells (RGCs) is central to the pathogenesis of optic neuropathies such as glaucoma. Increased RGC cAMP signaling is neuroprotective. We have shown that displacement of the cAMP-specific phosphodiesterase PDE4D3 from an RGC perinuclear compartment by expression of the modified PDE4D3 N-terminal peptide 4D3(E) increases perinuclear cAMP and protein kinase A activity in cultured neurons and in vivo RGC survival after optic nerve crush (ONC) injury. To explore mechanisms by which PDE4D3 displacement promotes neuroprotection, in this study mice intravitreally injected with an adeno-associated virus to express an mCherry-tagged 4D3(E) peptide were subjected to ONC injury and analyzed by single cell RNA-sequencing (scRNA-seq). 4D3(E)-mCherry expression was associated with an attenuation of injury-induced changes in gene expression, thereby supporting the hypothesis that enhanced perinuclear PKA signaling promotes neuroprotective RGC gene expression.

Perioperative and oncologic outcomes of robot-assisted versus open surgery for pancreatic ductal adenocarcinoma: a systematic review and meta-analysis.

This systematic review and meta-analysis aimed to compare perioperative and oncologic outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) treated with robotic-assisted surgery versus open laparotomy. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Randomized controlled trials (RCTs) and cohort studies up to June 15, 2024, were identified using PubMed, EMBASE, and Google Scholar. Additionally, reference lists of included studies, relevant review articles, and clinical guidelines were manually searched. The primary outcomes evaluated were length of stay, 90-day mortality, postoperative pancreatic fistula (POPF), and Post-pancreatectomy haemorrhage (PPH). Secondary outcomes included estimated blood loss, reoperation rate, lymph node yield, and operative time. The final analysis included 10 retrospective cohort studies involving 23,272 patients (2,179 robotic-assisted and 21,093 open surgery). There were no significant differences between the two procedures in terms of postoperative pancreatic fistula, Post-pancreatectomy haemorrhage, lymph node yield, and operative time. However, patients undergoing robotic-assisted surgery had shorter lengths of stay, lower 90-day mortality, and less estimated blood loss compared to those undergoing open surgery. The reoperation rate was higher for the robotic-assisted group. Robotic-assisted surgery for pancreatic ductal adenocarcinoma is safe and feasible. Compared to open surgery, it offers better perioperative and short-term oncologic outcomes, but with a higher risk of reoperation.

Adaptive Space Search-based Molecular Evolution Optimization Algorithm.

MOTIVATION: In drug development process, a significant portion of budget and research time are dedicated to the lead compound optimization procedure in order to identify potential drugs. This procedure focuses on enhancing the pharmacological and bioactive properties of compounds by optimizing their local substructures. However, due to the vast and discrete chemical structure space and the unpredictable element combinations within this space, the optimization process is inherently complex. Various structure enumeration-based combinatorial optimization methods have shown certain advantages. However, they still have limitations. Those methods fail to consider the differences between molecules and struggle to explore the unknown outer search space. RESULTS: In this study, we propose an adaptive space search-based molecular evolution optimization algorithm (ASSMOEA). It consists of three key modules: construction of molecule-specific search space, molecular evolutionary optimization, and adaptive expansion of molecule-specific search space. Specifically, we design a fragment similarity tree in molecule-specific search space, and apply a dynamic mutation strategy in this space to guide molecular optimization. Then we utilize an encoder-encoder structure to adaptively expand the space. Those three modules are circled iteratively to optimize molecules. Our experiments demonstrate that ASSMOEA outperforms existing methods in terms of molecular optimization. It not only enhances the efficiency of the molecular optimization process, but also exhibits a robust ability to search for correct solutions. AVAILABILITY AND IMPLEMENTATION: The code is freely available on the web at https://github.com/bbbbb-b/MEOAFST. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Vacancies-Induced Delocalized States Cobalt Phosphide for Binder-Free Anode Toward Stable and High-Rate Sodium-Ion Batteries.

Metal phosphides with easy synthesis, controllable morphology, and high capacity are considered as potential anodes for sodium-ion batteries (SIBs). However, the inherent shortcomings of metal phosphating materials, such as conductivity, kinetics, volume strain, etc are not satisfactory, which hinders their large-scale application. Here, a CoP@carbon nanofibers-composite containing rich Co─N─C heterointerface and phosphorus vacancies grown on carbon cloth (CoP1-x@MEC) is synthesized as SIB anode to accomplish extraordinary capacity and ultra-long cycle life. The hybrid composite nanoreactor effectively impregnates defective CoP as active reaction center while offering Co─N─C layer to buffer the volume expansion during charge-discharge process. These vast active interfaces, favored electrolyte infiltration, and a well-structured ion-electron transport network synergistically improve Na+ storage and electrode kinetics. By virtue of these superiorities, CoP1-x@MEC binder-free anode delivers superb SIBs performance including a high areal capacity (2.47 mAh cm-2@0.2 mA cm-2), high rate capability (0.443 mAh cm-2@6 mA cm-2), and long cycling stability (300 cycles without decay), thus holding great promise for inexpensive binder-free anode-based SIBs for practical applications.

Neoadjuvant chemoimmunotherapy for small cell carcinoma of the esophagus: Clinical efficacy and biomarker exploration.

Small cell carcinoma of the esophagus (SCCE) is a rare and highly malignant type of esophageal cancer with no standard treatment, facing challenges of resistance to conventional therapies. This study presents the cases of one extensive-stage and two limited-stage SCCE patients treated with chemoimmunotherapy. The two limited-stage patients underwent surgery post-treatment and experienced notable and enduring positive responses. This represents the first documented application of neoadjuvant chemoimmunotherapy in limited-stage SCCE patients. Additionally, comprehensive immunohistochemical analysis and whole exome sequencing were performed on the case patients. The findings revealed that infiltration of CD8+ T cells and PD-L1 expression in the SCCE tumor were key factors for favorable responses in SCCE patients receiving chemoimmunotherapy.

Biomimetic bimodal haptic perception using triboelectric effect.

Multimodal haptic perception is essential for enhancing perceptual experiences in augmented reality applications. To date, several artificial tactile interfaces have been developed to perceive pressure and precontact signals, while simultaneously detecting object type and softness with quantified modulus still remains challenging. Here, inspired by the campaniform sensilla on insect antennae, we proposed a hemispherical bimodal intelligent tactile sensor (BITS) array using the triboelectric effect. The system is capable of softness identification, modulus quantification, and material type recognition. In principle, due to the varied deformability of materials, the BITS generates unique triboelectric output fingerprints when in contact with the tested object. Furthermore, owing to the different electron affinities, the BITS array can accurately recognize material type (99.4% accuracy), facilitating softness recognition (100% accuracy) and modulus quantification. It is promising that the BITS based on the triboelectric effect has the potential to be miniaturized to provide real-time accurate haptic information as an artificial antenna toward applications of human-machine integration.

An antibacterial film using κ-carrageenan loaded with benzyl isothiocyanate nanoemulsion: Characterization and application in beef preservation.

Benzyl isothiocyanate (BITC) is a naturally active bacteriostatic substance and κ-carrageenan (KC) is a good film-forming substrate. In the present study, a nanoemulsion incorporating BITC was fabricated with a particle size of 224.1 nm and an encapsulation efficiency of 69.2 %. Subsequently, the acquired BITC nanoemulsion (BITC-NE) was incorporated into the KC-based film, and the light transmittance of the prepared composite films was lower than that of the pure KC film. Fourier transform infrared spectroscopy and scanning electron microscopy revealed that BITC-NE was compatible with the KC matrix. BITC-NE incorporation enhanced the tensile strength of the KC-based films by 33.7 %, decreased the elongation at break by 33.8 %, decreased the water vapor permeability by 60.1 %, increased the maximum thermal degradation temperature by 48.8 %, and decreased the oxygen permeability by 42 % (p < 0.05). Furthermore, the composite films showed enhanced antimicrobial activity against Staphylococcus aureus, Salmonella typhimurium, and Pseudomonas fluorescens. The developed KC-based composite films were applied to wrap raw beef, which significantly delayed the increase in total viable count, total volatile base nitrogen content, and thiobarbituric acid reactive substances, and prolonged the shelf-life of the raw beef by up to 10 days. These results indicated that the composite films prepared by incorporating BITC nanoemulsions into KC matrices have great antimicrobial application potential.

Photoinduced copper catalyzed nitrogen-to-alkyl radical relay Sonogashira-type coupling of o-alkylbenzamides with alkynes.

This report describes a copper-catalyzed, photoinduced N-to-alkyl radical relay Sonogashira-type reactions at benzylic sites in o-alkylbenzamides with alkynes. The process employs an N-to-alkyl radical mechanism, initiated through the copper-catalyzed reductive generation of nitrogen radicals. Radical translocation is facilitated by a 1,5-hydrogen atom transfer (1,5-HAT), leading to the formation of translocated carbon radicals. These radicals are then subjected to copper-catalyzed alkynylation. The methodology exhibits broad sub-strate scope and applicability to the synthesis of complex natural products.

Associations of parity and cognitive decline, depression, and chronic comorbidity in West China: Results from WCHAT study.

OBJECTIVE: To investigate the associations between parity (the number of offspring a female has borne) and cognitive function, depression, and chronic comorbidity in Western China. METHODS: A total of 846 women aged 50-55 years were included in the current analysis. Cognitive status was measured using a 10-item short portable mental status questionnaire (SPMSQ). Depressive symptoms were assessed using the 15-item geriatric depression scale (GDS-15). Other characteristics were self-reported. The associations between parity and cognitive decline, depression, and chronic comorbidity were analyzed using univariable and multivariable models. Multivariable models were adjusted for age, ethnic group, occupation, marital status, educational level, lifestyle factors, and sleeping time. RESULTS: Among the enrolled women, 26.71% were either childless or had one child, 47.40% had two children, 18.32% had three children, and 7.57% had ≥4 children. Compared to women with low parity, women with two or more children exhibited a higher risk of cognitive decline. Moreover, having four or more children was significantly associated with depression and chronic comorbidity. After adjusting covariates, women with three or more children exhibited a higher risk of cognitive decline than those with low parity. However, high parity was not significantly associated with depression or chronic comorbidity after adjustment for covariates. CONCLUSION: Our study showed that ≥3 children was associated with cognitive decline in women. Longitudinal studies are needed to evaluate this conclusion and to investigate the mechanisms involved. More importantly, families and societies should pay more attention to women's long-term health outcomes related to fertility.

Quercetin inhibits hypertonicity-induced inflammatory injury in human corneal epithelial cells via the PTEN/PI3K/AKT pathway.

Dry eye is a prevalent ophthalmic disease. Ocular surface inflammation in the hyperosmolar environment of the tear film is critical in dry eye progression. Quercetin has strong anti-inflammatory effects; however, its exact mechanism of action in dry eye is not fully understood. Therefore, this study investigated whether quercetin could inhibit the damage sustained to human corneal epithelial cells (HCECs) in a hyperosmolar environment through its anti-inflammatory effects. HCECs were cultured in a complete medium and were divided into four groups: normal, model, quercetin, and inhibitor. The proliferation of HCECs was detected by Ki67 staining; the expression levels of PTEN, p-PI3K and p-AKT were detected by Western blotting and immunofluorescence staining; the relative mRNA expression levels of PTEN, PI3K, AKT, IL-6 and TNF-ɑ were detected by quantitative real-time PCR; the relative expression levels of IL-6 and TNF-α were detected by enzyme-linked immunosorbent assay. In this study, the proliferation of HCECs in the model group was found to be significantly inhibited compared with that in the normal group; however, quercetin was effective in improving the proliferation of HCECs, decreasing the relative expression of p-PI3K, p-AKT, IL-6, TNF-ɑ as well as increasing PTEN. In conclusion, this study demonstrated that quercetin could promote the proliferation of HCECs and reduce the expression of inflammatory factors by inhibiting the PTEN/PI3K/AKT pathway in the hyperosmolarity-induced HCECs model.

Evolutionary Multiobjective Molecule Optimization in an Implicit Chemical Space.

Optimization techniques play a pivotal role in advancing drug development, serving as the foundation of numerous generative methods tailored to efficiently design optimized molecules derived from existing lead compounds. However, existing methods often encounter difficulties in generating diverse, novel, and high-property molecules that simultaneously optimize multiple drug properties. To overcome this bottleneck, we propose a multiobjective molecule optimization framework (MOMO). MOMO employs a specially designed Pareto-based multiproperty evaluation strategy at the molecular sequence level to guide the evolutionary search in an implicit chemical space. A comparative analysis of MOMO with five state-of-the-art methods across two benchmark multiproperty molecule optimization tasks reveals that MOMO markedly outperforms them in terms of diversity, novelty, and optimized properties. The practical applicability of MOMO in drug discovery has also been validated on four challenging tasks in the real-world discovery problem. These results suggest that MOMO can provide a useful tool to facilitate molecule optimization problems with multiple properties.

Atrial fibrillation accelerates functional decline in older adults: a 15-year follow-up population-based study.

AIMS: Atrial fibrillation (AF) has been associated with functional impairment. However, the role exerted by AF on the long-term trajectories of functional mobility remains to be elucidated. This study aimed to evaluate the impact of AF on functional mobility by tracing walking speed (WS) trajectories over 15 years of follow-up in a population-based cohort of individuals aged 60+ years. METHODS AND RESULTS: This population-based cohort study included 3141 community-dwelling participants (mean age 73.7 years; 63.6% women) from the Swedish National Study on Aging and Care in Kungsholmen, who were regularly examined from 2001-2004 to 2016-2019. Functional mobility was assessed by measuring WS in a standardized way. The association between AF and WS trajectories was assessed by multivariable joint models accounting for the longitudinal dropouts due to death. Stratified analyses by demographic and clinical factors were performed. The effect-modifying role of oral anticoagulant therapy (OAC), incident heart failure (HF), and incident stroke was finally investigated. At baseline, 285 (9.1%) participants were ascertained to have AF. A faster annual WS decline was observed in persons with AF than in non-AF peers (adjusted ß coefficient per year = -0.011, 95% confidence interval: -0.016 to -0.005). Incident HF and stroke were associated with greater WS decline in participants with AF. OAC use was not associated with a slower functional decline. CONCLUSION: Atrial fibrillation is associated with a faster physical function decline in older individuals. Incident HF and stroke possibly accelerate WS decline over time in AF participants.

[Research on alien invasive plants in Jingzhou County, Hunan Province, China]. / æ¹–å—çœé–å·žåŽ¿å¤–æ¥å ¥ä¾µæ¤ç‰©ç ”ç©¶.

Harm from alien invasive plants is increasing in Jingzhou County, Hunan Province. Based on a one-year field investigation and available literature, we investigated species composition, origin, flora, degree of harm and distribution pattern of invasive plants in the county. The results showed that there were 34 invasive plant species from 27 genera and 16 families in this County. The dominant invasive species belonged to Asteraceae (8 species) and Amaranthaceae (6 species), which accounted for 23.5% and 17.7%, respectively. The majority of invasive plants originated from South America (45.7%) and North America (30.4%). Tropical flora showed a significantly higher representation than temperate flora, signifying robust tropical characteristics amongst the invasive plant population. Based on hazard level classification, we recognized four types as malicious invasion (Level 1): Alternanthera philoxeroides, Erigeron annuus, E. canadensis, and Xanthium chinense. In addition, five types were classified as severe invasion (Level 2), eight types as local invasion (Level 3), fifteen types as general invasion (Level 4), while two types were still under observation (Level 5). The pattern of distribution demonstrated that invasive plants in Jingzhou County mostly spread along the verges of transportation roads, in human settlements, and in a few areas of water flow. The higher levels of invasion damage were principally concentrated in the central part of Jingzhou County.

Clinically used drug arsenic trioxide targets XIAP and overcomes apoptosis resistance in an organoid-based preclinical cancer model.

Drug resistance in tumor cells remains a persistent clinical challenge in the pursuit of effective anticancer therapy. XIAP, a member of the inhibitor of apoptosis protein (IAP) family, suppresses apoptosis via its Baculovirus IAP Repeat (BIR) domains and is responsible for drug resistance in various human cancers. Therefore, XIAP has attracted significant attention as a potential therapeutic target. However, no XIAP inhibitor is available for clinical use to date. In this study, we surprisingly observed that arsenic trioxide (ATO) induced a rapid depletion of XIAP in different cancer cells. Mechanistic studies revealed that arsenic attacked the cysteine residues of BIR domains and directly bound to XIAP, resulting in the release of zinc ions from this protein. Arsenic-XIAP binding suppressed the normal anti-apoptosis functions of BIR domains, and led to the ubiquitination-dependent degradation of XIAP. Importantly, we further demonstrate that arsenic sensitized a variety of apoptosis-resistant cancer cells, including patient-derived colon cancer organoids, to the chemotherapy drug using cisplatin as a showcase. These findings suggest that targeting XIAP with ATO offers an attractive strategy for combating apoptosis-resistant cancers in clinical practice.