Opportunities and Challenges in the Development of Antibody-Drug Conjugate for Triple-Negative Breast Cancer: The Diverse Choices and Changing Needs.

Triple-negative breast cancer (TNBC) is a highly heterogeneous breast cancer subtype, which is also characterized by the aggressive phenotype, high recurrence rate, and poor prognosis. Antibody-drug conjugate (ADC) is a monoclonal antibody with a cytotoxic payload connected by a linker. ADC is gaining more and more attention as a targeted anti-cancer agent. Clinical studies of emerging ADC drugs such as sacituzumab govitecan and trastuzumab deruxtecan in patients with metastatic breast cancer (including TNBC) are progressing rapidly. In view of its excellent clinical efficacy and good tolerability, Sacituzumab govitecan gained accelerated approval by the FDA for the treatment of advanced metastatic TNBC in 2020. This review discusses the treatment status and challenges in TNBC, with an emphasis on the current status of ADC development and clinical trials in TNBC and metastatic breast cancer. We also summarize the clinical experience and future exploration directions of ADC development for TNBC patients.

Discovery of a Series of 4-Amide-thiophene-2-carboxyl Derivatives as Highly Potent P2Y14 Receptor Antagonists for Inflammatory Bowel Disease Treatment.

The P2Y14 receptor has been proven to be a potential target for IBD. Herein, we designed and synthesized a series of 4-amide-thiophene-2-carboxyl derivatives as novel potent P2Y14 receptor antagonists based on the scaffold hopping strategy. The optimized compound 39 (5-((5-fluoropyridin-2-yl)oxy)-4-(4-methylbenzamido)thiophene-2-carboxylic acid) exhibited subnanomolar antagonistic activity (IC50: 0.40 nM). Moreover, compound 39 demonstrated notably improved solubility, liver microsomal stability, and oral bioavailability. Fluorescent ligand binding assay confirmed that 39 has the binding ability to the P2Y14 receptor, and molecular dynamics (MD) simulations revealed the formation of a unique intramolecular hydrogen bond (IMHB) in the binding conformation. In the experimental colitis mouse model, compound 39 showed a remarkable anti-IBD effect even at low doses. Compound 39, with a potent anti-IBD effect and favorable druggability, can be a promising candidate for further research. In addition, this work lays a strong foundation for the development of P2Y14 receptor antagonists and the therapeutic strategy for IBD.

A two-site Kitaev chain in a two-dimensional electron gas.

Artificial Kitaev chains can be used to engineer Majorana bound states (MBSs) in superconductor-semiconductor hybrids1-4. In this work, we realize a two-site Kitaev chain in a two-dimensional electron gas by coupling two quantum dots through a region proximitized by a superconductor. We demonstrate systematic control over inter-dot couplings through in-plane rotations of the magnetic field and via electrostatic gating of the proximitized region. This allows us to tune the system to sweet spots in parameter space, where robust correlated zero-bias conductance peaks are observed in tunnelling spectroscopy. To study the extent of hybridization between localized MBSs, we probe the evolution of the energy spectrum with magnetic field and estimate the Majorana polarization, an important metric for Majorana-based qubits5,6. The implementation of a Kitaev chain on a scalable and flexible two-dimensional platform provides a realistic path towards more advanced experiments that require manipulation and readout of multiple MBSs.

Anterior segment optical coherence tomography for superficial keratectomy.

PURPOSE: To report the use of anterior segment optical coherence tomography (AS-OCT) for superficial keratectomy (SK) in anterior corneal opacity. METHODS: The characteristics of 43 eyes (39 patients) with various lesions responsible for anterior corneal opacity were included in this retrospective non-comparative study. AS-OCT was performed on all eyes before surgery. The thickness of corneal opacity and the underlying healthy stroma were measured. SK was performed on each individual. RESULTS: Four types of anterior corneal opacity were evaluated, including corneal degeneration (26/43), Reis-Bücklers corneal dystrophy (8/43), alkali burn (1/43) and corneal tumors (8/43). Based on AS-OCT images, all eyes showed abnormal hyper-reflective signals in the superficial cornea to less than one-third of the normal corneal thickness in the deepest corneal opacity. All 43 eyes underwent an SK procedure. In addition, 1 eye with alkali burns and 7 eyes with corneal tumors were combined with amniotic membrane transplantation. All eyes restored transparency without significant complications. CONCLUSION: AS-OCT is a valuable method for objective preoperative and noninvasive assessments of anterior corneal opacities and is useful for guiding SK.

Thermodynamic modeling of freeze pretreatment in the destruction of rice straw structure combined with alkaline-hydrothermal method for enzymatic hydrolysis.

Freeze pretreatment combined with alkaline-hydrothermal method of rice straw for enzymatic hydrolysis was studied. Crystallization stress in the rice stem pores caused by water freezing at -20- -40 °C was modeled to illustrate the destruction mechanism. The stress was calculated as 22.5-38.3 MPa that were higher than the tensile yield stress of untreated stems (3.0 MPa), indicating ice formation damaging pore structure. After freeze at -20 °C, rice straw was further hydrothermally treated at 190 °C with 0.4 M Na2CO3, achieving 72.0 % lignin removal and 97.2 % cellulose recovery. Glucose yield rose to 91.1 % by 4.3 times after 24 h hydrolysis at 10 FPU loading of Cellic®CTec2 cellulase. The specific surface area of rice straw was 2.6 m2/g increased by 1.2 times after freeze. Freeze combined with alkaline-hydrothermal treatment is a green and energy-efficient method for improving enzymatic hydrolysis.

Specific convulsions and brain damage in children hospitalized for Omicron BA.5 infection: an observational study using two cohorts.

BACKGROUND: SARS-CoV-2 continues to mutate over time, and reports on children infected with Omicron BA.5 are limited. We aimed to analyze the specific symptoms of Omicron-infected children and to improve patient care. METHODS: We selected 315 consecutively hospitalized children with Omicron BA.5 and 16,744 non-Omicron-infected febrile children visiting the fever clinic at our hospital between December 8 and 30, 2022. Specific convulsions and body temperatures were compared between the two cohorts. We analyzed potential associations between convulsions and vaccination, and additionally evaluated the brain damage among severe Omicron-infected children. RESULTS: Convulsion rates (97.5% vs. 4.3%, P < 0.001) and frequencies (median: 2.0 vs. 1.6, P < 0.001) significantly differed between Omicron-infected and non-Omicron-infected febrile children. The body temperatures of Omicron-infected children were significantly higher during convulsions than when they were not convulsing and those of non-Omicron-infected febrile children during convulsions (median: 39.5 vs. 38.2 and 38.6 °C, both P < 0.001). In the three Omicron-subgroups, the temperature during convulsions was proportional to the percentage of patients and significantly differed ( P < 0.001), while not in the three non-Omicron-subgroups ( P = 0.244). The convulsion frequency was lower in the 55 vaccinated children compared to the 260 non-vaccinated children (average: 1.8 vs. 2.1, P < 0.001). The vaccination dose and convulsion frequency in Omicron-infected children were significantly correlated ( P < 0.001). Fifteen of the 112 severe Omicron cases had brain damage. CONCLUSIONS: Omicron-infected children experience higher body temperatures and frequencies during convulsions than those of non-Omicron-infected febrile children. We additionally found evidence of brain damage caused by infection with omicron BA.5. Vaccination and prompt fever reduction may relieve symptoms.

LTA and PGN from Bacillus siamensis can alleviate soybean meal-induced enteritis and microbiota dysbiosis in Lateolabrax maculatus.

An eight-week feeding trial was designed to assess which component of commensal Bacillus siamensis LF4 can mitigate SBM-induced enteritis and microbiota dysbiosis in spotted seabass (Lateolabrax maculatus) based on TLRs-MAPKs/NF-кB signaling pathways. Fish continuously fed low SBM (containing 16 % SBM) and high SBM (containing 40 % SBM) diets were used as positive (FM group) and negative (SBM group) control, respectively. After feeding high SBM diet for 28 days, fish were supplemented with B. siamensis LF4-derived whole cell wall (CW), cell wall protein (CWP), lipoteichoic acid (LTA) or peptidoglycan (PGN) until 56 days. The results showed that a high inclusion of SBM in the diet caused enteritis, characterized with significantly (P < 0.05) decreased muscular thickness, villus height, villus width, atrophied and loosely arranged microvillus. Moreover, high SBM inclusion induced an up-regulation of pro-inflammatory cytokines and a down-regulation of occludin, E-cadherin, anti-inflammatory cytokines, apoptosis related genes and antimicrobial peptides. However, dietary supplementation with CW, LTA, and PGN of B. siamensis LF4 could effectively alleviate enteritis caused by a high level of dietary SBM. Additionally, CWP and PGN administration increased beneficial Cetobacterium and decreased pathogenic Plesiomonas and Brevinema, while dietary LTA decreased Plesiomonas and Brevinema, suggesting that CWP, LTA and PGN positively modulated intestinal microbiota in spotted seabass. Furthermore, CW, LTA, and PGN application significantly stimulated TLR2, TLR5 and MyD88 expressions, and inhibited the downstream p38 and NF-κB signaling. Taken together, these results suggest that LTA and PGN from B. siamensis LF4 could alleviate soybean meal-induced enteritis and microbiota dysbiosis in L. maculatus, and p38 MAPK/NF-κB pathways might be involved in those processes.

Spatial distribution of Japanese encephalitis cases and correlated geo-environmental factors in southern and northern counties of China.

Japanese encephalitis (JE) is a mosquito-borne disease with a spatial distribution that is linked to geo-environmental factors. The spatial distribution of JE cases and correlated geo-environmental factors were investigated in two critical counties in southern and northern China. Based on maps, enhanced thematic mapper (ETM) remote sensing datasets from Landsat and spatial datasets of JE cases, spatial distribution and spatial cluster analyses of JE cases at the village scale were performed by using the standard deviational ellipse and Ripleys K-function. Global and regional spatial cluster analyses of JE cases were also performed by using Moran's index. Regression analysis was used to analyze the relationships between geo-environmental characteristics and the risk of JE cases. At the study sites, the JE cases were not spatially clustered at the village or district (global) level, whereas there was a spatial cluster at the district (local) level. Diversity-related features for JE patients at the district and village levels were detected at two sites. In the southern counties, the distance of a village from a road was related to the village-level JE risk (OR: 0.530, 95 CI: 0.297-0.947, P = 0.032), and the number of township-level JE cases was linked to the distance of the district center from the road (R =-0.467, P = 0.025) and road length (R = 0.516, P = 0.012) in the administrative area. In northern China, the modified normalized difference water index (MNDWI) in the 5 km buffer around the village was related to village-level JE risk (OR: 0.702, 95% CI: 0.524-0.940, P = 0.018), and the number of township-level JE cases was related to the MNDWI in the administrative region (R =-0.522, P = 0.038). This study elucidates the spatial distribution patterns of JE cases and risk, as well as correlated geo-environmental features, at various spatial scales. This study will significantly assist the JE control efforts of the local Centers for Disease Control and Prevention (CDC), which is the base-level CDC, particularly concerning the allocation of medicine and medical staff, the development of immunological plans, and the allocation of pesticides and other control measures for the mosquito vectors of JE.

Examining the paradox: increased malaria risk in children under 5 in female-headed households in Nigeria.

BACKGROUND: Nigeria is facing a severe malaria crisis, accounting for a significant proportion of global cases and deaths of malaria. This study aimed to investigate the differences between female-headed households (FHHs) and male-headed households (MHHs) and their impact on malaria risk among children under five (U5) in Nigeria. METHODS: Data from the 2021 Nigeria Malaria Indicator Survey (NMIS) were used for this cross-sectional study. A representative sample of 10,988 households was analysed, with key variables subjected to frequency calculations, descriptive statistics, and bivariate analyses using t-tests and chi-square analyses to compare the differences between FHHs and MHHs. RESULTS: Among all participants, 92.1% (N = 10,126) reported residing in male-headed households, while 7.8% (N = 862) reported living in female-headed households. MHHs were significantly more likely to own insecticide-treated bed nets (ITNs) than FHHs (64.7% vs. 53.6%, P < 0.001). U5 children in MHHs had a greater likelihood of sleeping under a bed net the night before the survey than U5 children in FHHs (35.3% vs. 30.0%, P < 0.05). The prevalence of fever in the previous two weeks among U5 children was similar in MHHs and FHHs (35.4% vs. 31.4%), and the testing rates for malaria among U5 children who experienced febrile episodes were higher in MHHs than FHHs (22.4% vs. 15.4%, P < 0.05). Although not statistically significant, FHHs exhibited a higher percentage of U5 children testing positive for malaria compared to MHHs (87.8% vs. 78.9%). On the other hand, FHHs had higher education levels, overall wealth index scores, and a larger presence in urban areas compared to MHHs (P < 0.001). Moreover, FHHs reported higher adherence to malaria prevention awareness (P < 0.001). CONCLUSION: In Nigeria, FHHs enjoy relatively better socioeconomic conditions and stronger awareness of malaria prevention compared to their male-headed counterparts. Contrary to expectations, FHHs are at an increased risk of malaria in children under 5 years old. This phenomenon is associated with entrenched gender inequality and the challenges women face in accessing critical assets. As women in FHHs bear the responsibility of income generation while caring for their children, it is crucial to prioritize interventions that address malaria management in FHHs to reduce both malaria incidence and mortality rates.

Clinical manifestation, lifestyle, and treatment patterns of chronic erosive gastritis: A multicenter real-world study in China.

BACKGROUND: Although chronic erosive gastritis (CEG) is common, its clinical characteristics have not been fully elucidated. The lack of consensus regarding its treatment has resulted in varied treatment regimens. AIM: To explore the clinical characteristics, treatment patterns, and short-term outcomes in CEG patients in China. METHODS: We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and pathology. Patients and treating physicians completed a questionnaire regarding history, endoscopic findings, and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of treatment. RESULTS: Three thousand five hundred sixty-three patients from 42 centers across 24 cities in China were included. Epigastric pain (68.0%), abdominal distension (62.6%), and postprandial fullness (47.5%) were the most common presenting symptoms. Gastritis was classified as chronic non-atrophic in 69.9% of patients. Among those with erosive lesions, 72.1% of patients had lesions in the antrum, 51.0% had multiple lesions, and 67.3% had superficial flat lesions. In patients with epigastric pain, the combination of a mucosal protective agent (MPA) and proton pump inhibitor was more effective. For those with postprandial fullness, acid regurgitation, early satiety, or nausea, a MPA appeared more promising. CONCLUSION: CEG is a multifactorial disease which is common in Asian patients and has non-specific symptoms. Gastroscopy may play a major role in its detection and diagnosis. Treatment should be individualized based on symptom profile.

The construction of genetics teaching resources related to colour blindness and their application in genetics teaching.

Red-green colour blindness is a classic example for the teaching of X-linked recessive inheritance in genetics course. However, there are lots of types of color vision deficiencies besides red-green colour blindness. Different color vision deficiencies caused by different genes may have different modes of inheritance. In recent years, many research achievements on colour blindness have been made. These achievements could be used as teaching resources in genetics course. Here, we summarize the construction of genetics teaching resources related to colour blindness and their application in genetics teaching in several chapters such as introduction, cellular and molecular basis of genetics, sex-linked inheritance, chromosomal aberration, gene mutation and advances in genetics. Teacher could use the resources in class or after class with different teaching methods such as questioning teaching method and task method. It may expand students' academic horizons and inspire students' interest in genetics besides grasping basic genetic knowledge.

Using the i-PARIHS theoretical framework to develop evidence implementation strategies for central venous catheter maintenance: a multi-site quality improvement project.

INTRODUCTION: Evidence-based nursing practice can reduce complications associated with central venous catheters (CVCs). In this project, the Integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework was considered an ideal theoretical instrument to identify facilitators and barriers to implementing evidence-based practice. METHODS: The project was conducted in pediatric intensive care units in six Chinese tertiary children's hospitals. Twenty-two audit criteria were obtained from best practice recommendations, and a baseline audit was conducted to assess current practice against best practice. Next, the i-PARIHS framework was used to identify facilitators and barriers to best practice and develop improvement strategies. A follow-up audit was then conducted to measure changes in compliance with best practices. RESULTS: Facilitators and barriers were identified at the innovation, recipient, and context levels. A comprehensive CVC maintenance strategy was then developed to apply the best evidence to nurses' clinical work. Of the 22 audit criteria, 17 showed significant improvement compared with the baseline audit. CONCLUSIONS: The i-PARIHS framework is an effective tool for developing targeted, evidence-based improvement strategies and applying these to the clinical setting. The quality of the nurses' clinical practice improved during CVC maintenance. However, there is no certainty that these positive results can be maintained, and long-term data are needed to verify this. SPANISH ABSTRACT: http://links.lww.com/IJEBH/A185.

[Research progress of traditional Chinese medicines as quorum sensing inhibitors in collaboration with antibiotics to inhibit drug-resistant bacteria].

Quorum sensing system regulates the expression of genes related to bacterial growth, metabolism and other behaviors by sensing bacterial density, and controls the unified action of the entire bacterial population. This mechanism can ensure the normal secretion of bacterial metabolites and the stability of the biofilm microenvironment, providing protection for the formation of biofilms and the normal growth and reproduction of bacteria. Traditional Chinese medicine, capable of quorum sensing inhibition, can inhibit the formation of bacterial biofilms, reduce bacterial resistance, and enhance the anti-infection ability of antibiotics when combined with antibiotics. In recent years, the combination of traditional Chinese and Western medicine in the treatment of drug-resistant bacterial infections has become a research hotspot. Starting with the associations between quorum sensing, biofilm and drug-resistant bacteria, this paper reviews the relevant studies about the combined application of traditional Chinese medicines as quorum sensing inhibitors with antibiotics in the treatment of drug-resistant bacteria. This review is expected to provide ideas for the development of new clinical treatment methods and novel anti-infection drugs.

Analysis of the impact of immunotherapy efficacy and safety in patients with gastric cancer and liver metastasis.

BACKGROUND: Gastric cancer (GC) is the fifth most common type of cancer and has the fourth highest death rate among all cancers. There is a lack of studies examining the impact of liver metastases on the effectiveness of immunotherapy in individuals diagnosed with GC. AIM: To investigate the influence of liver metastases on the effectiveness and safety of immunotherapy in patients with advanced GC. METHODS: This retrospective investigation collected clinical data of patients with advanced stomach cancer who had immunotherapy at our hospital from February 2021 to January 2023. The baseline attributes were compared using either the Chi-square test or the Fisher exact probability method. The chi-square test and Kaplan-Meier survival analysis were employed to assess the therapeutic efficacy and survival duration in GC patients with and without liver metastases. RESULTS: The analysis comprised 48 patients diagnosed with advanced GC, who were categorized into two groups: A liver metastasis cohort (n = 20) and a non-liver metastatic cohort (n = 28). Patients with liver metastasis exhibited a more deteriorated physical condition compared to those without liver metastasis. The objective response rates in the cohort with metastasis and the cohort without metastasis were 15.0% and 35.7% (P > 0.05), respectively. Similarly, the disease control rates in these two cohorts were 65.0% and 82.1% (P > 0.05), respectively. The median progression-free survival was 5.0 months in one group and 11.2 months in the other group, with a hazard ratio of 0.40 and a significance level (P) less than 0.05. The median overall survival was 12.0 months in one group and 19.0 months in the other group, with a significance level (P) greater than 0.05. CONCLUSION: Immunotherapy is less effective in GC patients with liver metastases compared to those without liver metastasis.

[Construction and Optimization of CD19 Chimeric Antigen Receptor T Cells Derived from C57BL/6J Mice].

OBJECTIVE: To explore the stimulation conditions, optimal culture time and infection time of C57BL/6J mice CD3+ T cells in vitro, so as to improve the infection efficiency of CD19 chimeric antigen receptor T cells (mCD19 CAR-T). METHODS: Purified C57BL/6J mice CD3+ T cells were cultured in anti-CD3/CD28 coated, anti-CD3 coated+soluble anti-CD28 and anti-CD3 coated, respectively. The cells were stimulated in above three conditions for 12 h and 24 h, following with 24 h, 48 h and 72 h incubation and then the number of cell clones was recorded. C57BL/6J mice CD3+ T cells were stimulated for 12 h, 24 h, and 36 h under the above three conditions, then interleukin (IL)-2 (100 U/ml) was added. The number of cell clones was recorded under microscope at 24 h, 48 h, and 72 h of culture. After 24 h of stimulation, CD3+ T cells derived from C57BL/6J mice were infected with retrovirus for 48 h to establish mCD19 CAR-T cells, and the percentage of GFP+ CAR-T cells was detected by flow cytometry. RESULTS: The infection efficiency of mCD19 CAR-T cells derived from C57BL/6J mice was only 5.23% under the optimized conditions of mCD19 CAR-T cells derived from BALB/c mice. The number of clones of C57BL/6J mice CD3+ T cells was the highest in anti-CD3 coated+soluble anti-CD28 group after stimulated for 24 h and followed cultured for 48 h. After 24 hours of stimulation under the above conditions and 48 hours of culture with IL-2, the number of T cell proliferating clones in the anti-CD3 coated+soluble anti-CD28 group was significantly increased compared with the same group without IL-2, and the infection efficiency of CAR-T cells in this group reached 17.63%±4.17%. CONCLUSION: The optimal conditions for constructing CAR-T cells from C57BL/6J mice CD3+ T cells are different from those of BABL/c mice. T cells stimulated by anti-CD3 coated+soluble anti-CD28+IL-2 can obtain mCD19 CAR-T cells with the highest efficiency after retrovirus infection.

Extracellular vesicles derived from mesenchymal stem cells mediate extracellular matrix remodeling in osteoarthritis through the transport of microRNA-29a.

BACKGROUND: Knee osteoarthritis (KOA) is a common orthopedic condition with an uncertain etiology, possibly involving genetics and biomechanics. Factors like changes in chondrocyte microenvironment, oxidative stress, inflammation, and immune responses affect KOA development. Early-stage treatment options primarily target symptom relief. Mesenchymal stem cells (MSCs) show promise for treatment, despite challenges. Recent research highlights microRNAs (miRNAs) within MSC-released extracellular vesicles that can potentially promote cartilage regeneration and hinder KOA progression. This suggests exosomes (Exos) as a promising avenue for future treatment. While these findings emphasize the need for effective KOA progression management, further safety and efficacy validation for Exos is essential. AIM: To explore miR-29a's role in KOA, we'll create miR-29a-loaded vesicles, testing for early treatment in rat models. METHODS: Extraction of bone marrow MSC-derived extracellular vesicles, preparation of engineered vesicles loaded with miR-29a using ultrasonication, and identification using quantitative reverse transcription polymerase chain reaction; after establishing a rat model of KOA, rats were randomly divided into three groups: Blank control group injected with saline, normal extracellular vesicle group injected with normal extracellular vesicle suspension, and engineered extracellular vesicle group injected with engineered extracellular vesicle suspension. The three groups were subjected to general behavioral observation analysis, imaging evaluation, gross histological observation evaluation, histological detection, and immunohistochemical detection to compare and evaluate the progress of various forms of arthritis. RESULTS: General behavioral observation results showed that the extracellular vesicle group and engineered extracellular vesicle group had better performance in all four indicators of pain, gait, joint mobility, and swelling compared to the blank control group. Additionally, the engineered extracellular vesicle group had better pain relief at 4 wk and better knee joint mobility at 8 wk compared to the normal extracellular vesicle group. Imaging examination results showed that the blank control group had the fastest progression of arthritis, the normal extracellular vesicle group had a relatively slower progression, and the engineered extracellular vesicle group had the slowest progression. Gross histological observation results showed that the blank control group had the most obvious signs of arthritis, the normal extracellular vesicle group showed signs of arthritis, and the engineered extracellular vesicle group showed no significant signs of arthritis. Using the Pelletier gross score evaluation, the engineered extracellular vesicle group had the slowest progression of arthritis. Results from two types of staining showed that the articular cartilage of rats in the normal extracellular vesicle and engineered extracellular vesicle groups was significantly better than that of the blank control group, and the engineered extracellular vesicle group had the best cartilage cell and joint surface condition. Immunohistochemical detection of type II collagen and proteoglycan showed that the extracellular matrix of cartilage cells in the normal extracellular vesicle and engineered extracellular vesicle groups was better than that of the blank control group. Compared to the normal extracellular vesicle group, the engineered extracellular vesicle group had a better regulatory effect on the extracellular matrix of cartilage cells. CONCLUSION: Engineered Exos loaded with miR-29a can exert anti-inflammatory effects and maintain extracellular matrix stability, thereby protecting articular cartilage, and slowing the progression of KOA.

Associations of residential greenness exposure and ambient air pollutants with newly-diagnosed drug-resistant tuberculosis cases.

Growing evidence has found the health protective effects of greenness exposure on tuberculosis (TB) and the impact of ambient air pollutants on TB drug-resistance. However, it remains unclear whether residential greenness is also beneficial to reduce TB drug-resistance, and whether air pollution modify the greenness-TB resistance relationship. We enrolled 5006 newly-diagnosed TB patients from Shandong, China, during 2014 to 2021. Normalized Difference Vegetation Index (NDVI) in 250 m and 500 m buffer around individuals' residential zone was used to assess greenness exposure. All patients were divided by quartiles of NDVI250-m and NDVI500-m (from low to high: Q1, Q2, Q3, Q4) respectively. Six logistic regression models (NDVI, NDVI + PM2.5/PM10/SO2/NO2/O3) were used to estimate the association of NDVI and TB drug-resistance when adjusting different air pollutants or not. All models were adjusted for age, gender, body mass index, complications, smoking, drinking, population density, nighttime light index, road density. Compared with participants in NDVI250-m Q1 and NDVI500-m Q1, other groups had lower rates of MDR-TB, PDR-TB, RFP-resistance, SM-resistance, RFP + SM resistance, INH + RFP + EMB + SM resistance. NDVI500-m reduced the risk of multidrug resistant tuberculosis (MDR-TB) and the adjusted odds ratio (aOR, 95% confidence interval, CI) compared with NDVI500-m Q1 were 0.736 (0.547-0.991) in NDVI + PM10 model, 0.733 (0.544-0.986) in NDVI + PM2.5 model, 0.735(0.546-0.99) in NDVI + SO2 model, 0.736 (0.546-0.991) in NDVI + NO2 model, respectively, P < 0.05. NDVI500-m contributed to a decreased risk of streptomycin (SM)-resistance. The aOR of rifampicin (RFP) + SM resistance were 0.132 (NDVI250-m, Q4 vs Q1, 95% CI: 0.03-0.578), 0.199 (NDVI500-m, Q3 vs. Q1, 95% CI: 0.057-0.688) and 0.264 (NDVI500-m, Q4 vs. Q1, 95% CI: 0.087-0.799). The adjusted ORs (Q2 vs. Q1, 95% CI) of isoniazid (INH) + RFP + ethambutol (EMB) + SM resistance in 500 m buffer were 0.276 (0.119-0.639) in NDVI model, 0.279 (0.11-0.705) in NDVI + PM10 model, 0.281 (0.111-0.713) in NDVI + PM2.5 model, 0.279 (0.11-0.709) in NDVI + SO2 model, 0.296 (0.117-0.754) in NDVI + NO2 model, 0.294 (0.116-0.748) in NDVI + O3 model, respectively. The study showed, for the first time, that residential greenness exposure in 500 m buffer is beneficial for reducing newly-diagnosed DR-TB (including PDR-RB, MDR-TB, MR-TB), and ambient air pollutants may partially mediate this association.

Retracted: Marchantin M Induces Apoptosis of Prostate Cancer Cells Through Endoplasmic Reticulum Stress.

The Editors of Medical Science Monitor wish to inform you that the above manuscript has been retracted from publication due to concerns with the credibility and originality of the study, the manuscript content, and the Figure images. Reference: Tian-Wei Zhang, Li Xing, Jun-Long Tang, Jing-Xiao Lu, Chun-Xiao Liu. Marchantin M Induces Apoptosis of Prostate Cancer Cells Through Endoplasmic Reticulum Stress. Med Sci Monit, 2015; 21: 3570-3576. DOI: 10.12659/MSM.894476.

The mechanism and experimental verification of Ixeris sonchifolia promoting apoptosis of hepatocellular carcinoma based on network pharmacology: Ixeris sonchifolia Induces Hepatocellular Carcinoma Apoptosis via the PI3K/AKT Pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ixeris sonchifolia alias Kudiezi, it was named Ixeris sonchifolia (Bunge) Hance, a synonym for Crepidiastrum sonchifolium (Bunge) Pak & Kawano in the https://www.iplant.cn/. And it was first published in J. Linn. Soc., Bot. 13: 108 (1873), which was named Ixeris sonchifolia (Maxim.) Hance in the MPNS (http://mpns.kew.org). As a widely distributed medicinal and edible wild plant, it possesses unique bitter-cold characteristics and constituents with various pharmacological activities. Its main antitumor substances, same as artemisinin and paclitaxel, are classified as terpenoids and have become research foci in recent years. However, its specific biological activity and role in antitumor treatment remain largely unclear. AIM OF THE STUDY: This study aimed to elucidate the molecular targets and potential mechanisms of hepatocellular carcinoma apoptosis induced by Ixeris sonchifolia. MATERIALS AND METHODS: We used network pharmacology methods to analyze and screen the active ingredients and possible underlying mechanisms of Ixeris sonchifolia in treating liver cancer and employed integrative time- and dose-dependent toxicity, transcriptomics, and molecular biology approaches to comprehensively verify the function of Ixeris sonchifolia extract (IsE) in human hepatoblastoma cell (HepG2) apoptosis and its potential mechanism. RESULTS: A total of 169 common targets were screened by network pharmacology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that IsE inhibited HepG2 cell activity in a time- and dose-dependent manner. Western blot analysis confirmed that IsE promoted HepG2 cell apoptosis by inhibiting the PI3K/AKT signaling pathway and that the PI3K/AKT inhibitor LY294002 also substantially enhanced IsE-induced apoptosis. The PI3K/AKT signaling pathway exhibited significant differences compared to that in the control group. CONCLUSION: Combining network pharmacology with experimental verification, IsE inhibited mitochondrial function and the PI3K/AKT pathway while inducing hepatoma cell apoptosis. IsE may have promising potential for liver cancer treatment and chemoprevention.

The effect of artificial light at night (ALAN) on the characteristics of diapause of Aedes albopictus.

BACKGROUND: Recently, the effect of artificial light at night (ALAN) on the physiology and behavior of insects has gradually attracted the attention of researchers and has become a new research topic. Aedes albopictus is an important vector that poses a great public health risk. Further studies on the diapause of Ae. albopictus can provide a basis for new vector control, and it is also worth exploring whether the effect of ALAN on the diapause of Ae. albopictus will provide a reference for the prevention and control of infectious diseases mediated by Ae. albopictus. METHODS: In this study, we experimentally studied the diapause characteristics of different geographical strains of Ae. albopictus under the interference of ALAN, explored the effect of ALAN on the diapause of Ae. albopictus and explored the molecular mechanism of ALAN on the diapause process through RNA-seq. RESULTS: As seen from the diapause incidence, Ae. albopictus of the same geographic strain showed a lower diapause incidence when exposed to ALAN. The differentially expressed genes (DEGs) were mainly enriched in signaling and metabolism-related pathways in the parental females and diapause eggs of the ALAN group. CONCLUSIONS: ALAN inhibits Ae. albopictus diapause. In the short photoperiod induced diapause of Ae. albopictus in temperate strain Beijing and subtropical strain Guangzhou, the disturbance of ALAN reduced the egg diapause rate and increased the egg hatching rate of Ae. albopictus, and the disturbance of ALAN also shortened the life cycle of Ae. albopictus eggs after hatching.