Maintaining moderate levels of hypochlorous acid promotes neural stem cell proliferation and differentiation in the recovery phase of stroke.

JOURNAL/nrgr/04.03/01300535-202503000-00029/figure1/v/2024-06-17T092413Z/r/image-tiff It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late stroke. Indeed, previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain tissue. Our previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke, but its specific role and mechanism are currently unclear. To simulate stroke in vivo, a middle cerebral artery occlusion rat model was established, with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic stroke. We found that in the early stage (within 24 hours) of ischemic stroke, neutrophils produced a large amount of hypochlorous acid, while in the recovery phase (10 days after stroke), microglia were activated and produced a small amount of hypochlorous acid. Further, in acute stroke in rats, hypochlorous acid production was prevented using a hypochlorous acid scavenger, taurine, or myeloperoxidase inhibitor, 4-aminobenzoic acid hydrazide. Our results showed that high levels of hypochlorous acid (200 µM) induced neuronal apoptosis after oxygen/glucose deprivation/reoxygenation. However, in the recovery phase of the middle cerebral artery occlusion model, a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and astrocytes. This suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion injury. Lower levels of hypochlorous acid (5 and 100 µM) promoted nuclear translocation of ß-catenin. By transfection of single-site mutation plasmids, we found that hypochlorous acid induced chlorination of the ß-catenin tyrosine 30 residue, which promoted nuclear translocation. Altogether, our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.

Actein ameliorates diet-induced obesity through the activation of AMPK-mediated white fat browning.

BACKGROUND: Targeting white adipose tissue (WAT) browning to increase systemic energy expenditure is a promising therapeutic strategy to combat obesity. Actein from Actaea cimicifuga L. has recently been reported to ameliorate high fat-induced hepatic steatosis. However, the effect of actein on diet-induced obesity merits more and further investigation. PURPOSE: We aimed to examine the anti-obesity potential of actein and unravel its actions on WAT browning. METHODS: The effect of actein on diet-induced obesity was evaluated using a high-fat diet model in C57BL/6 mice. Systemic energy expenditure of mice was measured with a combined indirect calorimetry system. Quantitative real-time PCR analyses were performed to investigate the mRNA levels of genes involved in thermogenesis, browning, and lipolysis. The protein levels were assessed by Western blot. Moreover, WAT explants and a transwell co-culture system consisting of SVFs and adipocytes were constructed to study the mechanisms of actein on promoting WAT browning and lipolysis. RESULTS: At a dosage of 5 mg/kg/d, actein not only protected mice against diet-induced obesity and insulin resistance, but also reversed pre-established obesity and glucose intolerance in mice. Meanwhile, actein facilitated systemic energy expenditure by activating WAT lipolysis and browning. Further, mechanistic studies revealed that actein indirectly induced epididymal adipocyte lipolysis and directly promoted a white-to-beige conversion of subcutaneous adipocytes by activating the AMPK signaling. CONCLUSION: Actein ameliorated diet-induced obesity and was discovered as a natural lead compound directly targeting white-to-beige conversion of subcutaneous adipocytes, suggesting the potential of developing new therapies for obesity and associated metabolic disorders.

Shield-armed probiotic delivery system based on co-deposition of poly-dopamine and poly-l-lysine helps Lactiplantibacillus plantarum relieve hyperuricemia.

Hyperuricemia (HUA) is a disease characterized by an abnormal metabolism of purine. Lactic acid bacteria (LAB) have attracted much attention for their safe and effective treatment of HUA by inhibiting xanthine oxidase (XOD) and regulating gut microbiota. However, the effectiveness of probiotics can be compromised by the harsh environment of the gastrointestinal tract. In preliminary experiments, Lactiplantibacillus plantarum DY1, which is generally regarded as safe (GRAS), can lower uric acid. We have devised a straightforward and efficient technique for encapsulating DY1 using a coating comprising polydopamine (PDA) co-deposited with poly-l-lysine (PLL) to obtain DY1@PDLL. TEM, SEM, FT-IR and DLS tests showed that DY1 was successfully coated. Incubate at SGF or SIF for 3 h, the number of viable bacteria of free probiotics and DY1@PDLL decreased by 0.92 and 0.46 log cfu/mL, 1.66 and 0.66 log cfu/mL, respectively. The fluorescence intensity of the intestines of the DY1@PDLL treated mice was 3.96 times that of free probiotic. Notably, DY1@PDLL can reduce the uric acid levels of HUA mice by 31.63 % and free probiotics by 18.72 % (≈1.69 times). DY1@PDLL could also regulate gut microbiota and serum metabolic profile. These findings unequivocally highlight the remarkable potential of DY1@PDLL as an exceptional oral probiotic delivery system.

The oncogenic role of EIF4A3/CDC20 axis in the endometrial cancer.

Eukaryotic initiation factor 4A-3 (EIF4A3) is a key component of the exon junction complex (EJC) and is extensively involved in RNA splicing, inducing mRNA decay, and regulating the cell cycle and apoptosis. However, the potential role of EIF4A3 in EC has not been comprehensively investigated and remains unknown. Here, we report that the expression level of EIF4A3 is dramatically elevated in endometrial cancer (EC) samples compared with normal EC samples via bioinformatics analysis and immunohistochemistry analysis, and that high expression of EIF4A3 promotes the proliferation, migration, and invasion of EC cells. Mechanistically, we found that high EIF4A3 expression stabilized cell division cyclin 20 (CDC20) mRNA, and high EIF4A3 expression induced pro-carcinogenic effects in EC cells that were efficiently antagonized upon knockdown of CDC20, as well as Apcin, an inhibitor of CDC20. These findings reveal a novel mechanism by which high expression of EIF4A3 induces CDC20 upregulation, thus leading to EC tumorigenesis and metastasis, indicating a potential treatment strategy for EC patients with high EIF4A3 expression using Apcin. KEY MESSAGES: The expression level of EIF4A3 was dramatically elevated in endometrial cancer (EC) samples compared with normal endometrial cancer samples. High EIF4A3 expression stabilized CDC20 mRNA, and high EIF4A3 expression induced pro-carcinogenic effect in EC cells which was efficiently antagonized upon knockdown of CDC20. Apcin, an inhibitor of CDC20, could effectively counteract high expression of EIF4A3 inducing EC tumourigenesis and metastasis, indicating the potential treatment strategy for EC patients with EIF4A3 high expression by using Apcin.

 Stromatolinea, a new diatrypaceous fungal genus (Ascomycota, Sordariomycetes, Xylariales, Diatrypaceae) from China.

Molecular phylogeny and morphological characteristics of collections of diatrypaceous fungi from Guizhou Province, China, lead to the establishment of a new genus, Stromatolinea, and the identification of four new species and two new combinations. The taxa were found growing on the dead culms of Phyllostachys bamboo. The new genus is distinguished by its well-developed, discrete linear stromata with yellow interior tissue and allantoid subhyaline ascospores. The newly described species are Stromatolineagrisea, S.guizhouensis, S.hydei, and S.xishuiensis. Additionally, two new combinations, Stromatolinealinearis and S.phaselina, are proposed based on comparative analysis and morphology. Phylogenetic analyses were conducted using ITS and TUB2 sequences. The study includes comprehensive morphological descriptions, illustrations, and a phylogenetic tree depicting the placement of the new taxa.

Efficacy of neoadjuvant chemotherapy combined with prophylactic intraperitoneal hyperthermic chemotherapy for patients diagnosed with clinical T4 gastric cancer who underwent laparoscopic radical gastrectomy: a retrospective cohort study based on propensity score matching.

BACKGROUND: Clinical T4 (cT4) stage gastric cancer presents with frequent postoperative recurrence and poor prognosis. This study is to evaluate the oncological efficacy of laparoscopic radical total gastrectomy combined with postoperative prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with cT4N + M0 gastric cancer who received neoadjuvant chemotherapy. METHODS: We reviewed the clinicopathological data of 174 patients with clinical T4 gastric cancer who underwent neoadjuvant chemotherapy followed by laparoscopic radical total gastrectomy between June 2017 and December 2021. Among them, 142 were included in the non-HIPEC group, and 32 in the HIPEC group. Patients in both groups were paired based on propensity score in a 2:1 ratio to assess disparities in tumor recurrence and long-term survival. RESULTS: After matching, there were no significant differences in the clinicopathological data between the two groups. The peritoneum (16.1%) and distant organs (10.9%) were the most frequent locations for recurrence. Prior to matching, the recurrence rates were similar at all sites for both groups. Compared with those in the non-HIPEC cohort, the recurrence rates at all sites, the lung, and the peritoneum were notably lower in the HIPEC cohort. Prior to matching, the 3-year overall survival and disease-free survival rates were similar between the two groups; following matching, the HIPEC group exhibited notably greater survival rates than did the non-HIPEC group. The disparities in survival rates between the groups became even more pronounced after conducting a stratified analysis among patients with stage III disease. CONCLUSIONS: Neoadjuvant chemotherapy combined with prophylactic HIPEC after laparoscopic radical gastrectomy can effectively reduce the rate of peritoneal metastasis in patients with cT4N + M0 advanced gastric cancer and significantly improve the prognosis of such patients, which is of great clinical value.

Interfacial Stabilization of Organic Electrochemical Transistors Conferred Using Polythiophene-Based Conjugated Block Copolymers with a Hydrophobic Coil Design.

The recent interest in developing low-cost, biocompatible, and lightweight bioelectronic devices has focused on organic electrochemical transistors (OECTs), which have the potential to fulfill these requirements. In this study, three types of poly(3-hexylthiophene) (P3HT)-based block copolymers (BCPs) incorporating different insulating blocks (poly(nbutyl acrylate) (PBA), polystyrene, and poly(ethylene oxide) (PEO)) were synthesized for application in OECTs. The morphological, crystallographic, and electrochemical properties of these BCPs are systematically investigated. Accordingly, P3HT-b-PBA demonstrates superior performance in the KCl-based aqueous electrolyte, with a higher product of mobility and capacitance (µC*) at 170 F s-1 cm-1 V-1 than that of the P3HT homopolymer at 58 F s-1 cm-1 V-1. P3HT-b-PBA exhibits better stability over 50 ON/OFF switching cycles than do other BCPs and P3HT homopolymers. With regard to the performance in the KPF6-based aqueous electrolyte, P3HT-b-PBA outperforms with a higher µC* of 9.2 F s-1 cm-1 V-1 than that of 8.6 F s-1 cm-1 V-1 observed from P3HT. Notably, both polymers exhibited almost no decay in device performance over 110 ON/OFF switching cycles. The strongly different performance of polymers in these two electrolytes is due to the side chain's hydrophobicity and interdigitated lamellar structures, thereby retarding the doping kinetics of the highly hydrated Cl- ions compared with the slightly hydrated PF6- ions. Concerning the improved performance of P3HT-b-PBA, this is attributed to its soft and hydrophobic backbone. Our morphological and crystallographic analyses reveal that P3HT-b-PBA experiences minimal structural disorder when swelled by the electrolyte, maintaining its original structure better than the P3HT homopolymer and the hydrophilic BCP of P3HT-b-PEO. The hydrophobic nature of P3HT-b-PBA contributes to the stability of its backbone structure, ensuring enhanced capacitance during the operation of the OECT operation. These findings provide reassurance about the stability and performance of P3HT-b-PBA in the field of OECT applications. In summary, this study represents the first exploration of P3HT-based BCPs for OECT applications and investigates their structure-performance relationships in mixed ionic-electronic conductors.

Associations of Gestational Exposure to Air Pollution and Polycyclic Aromatic Hydrocarbons with Placental Inflammation.

Restricted fetal growth (RFG) is a leading contributor to perinatal mortality and has been associated with gestational exposure to air pollution, such as fine particulate matter (PM2.5), nitrogen dioxide (NO2), and polycyclic aromatic hydrocarbons (PAHs). This study examines the association between trimester-specific and weekly means of air pollution throughout gestation and placental inflammatory markers at delivery. In a prospective cohort study of 263 pregnant women in Rochester, NY, we measured interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in placental tissue and estimated gestational exposure to PM2.5 and NO2 using a high-resolution spatial-temporal model. Exposure to PAHs was estimated using urinary 1-hydroxypyrene (1-OHP) concentrations collected once per trimester. Using distributed lag models with a penalized spline function, each interquartile range (2.6 µg/m3) increase in PM2.5 concentration during gestational weeks 6-11 was associated with decreased placental IL-6 levels (-22.2%, 95% CI: -39.0%, -0.64%). Using multiple linear regression models, each interquartile range increase of 1-OHP was associated with an increase in TNF-α in the first trimester (58.5%, 95% CI: 20.7%, 74.2%), third trimester (22.9%, 95% CI: 0.04%, 49.5%), and entire pregnancy (29.6%, 95%CI: 3.9%,60.6%). Our results suggest gestational exposure to air pollution may alter the inflammatory environment of the placenta at delivery.

Integrin α6-containing extracellular vesicles promote lymphatic remodelling for pre-metastatic niche formation in lymph nodes via interplay with CD151.

Heterogeneous extracellular vesicles (EVs) from various types of tumours are acknowledged for inducing the formation of pre-metastatic "niches" in draining lymph nodes (LNs) to promote lymphatic metastasis. In order to identify the specific subpopulations of EVs involved, we performed high-resolution proteomic analysis combined with nanoflow cytometry of bladder cancer (BCa) tissue-derived EVs to identify a novel subset of tumour-derived EVs that contain integrin α6 (ITGA6+EVs) and revealed the positive correlation of ITGA6+EVs with the formation of pre-metastatic niche in draining LNs and lymphatic metastasis in multicentre clinical analysis of 820-case BCa patients. BCa-derived ITGA6+EVs induced E-selectin (SELE)-marked lymphatic remodelling pre-metastatic niche and promoted metastasis in draining LNs through delivering cargo circRNA-LIPAR to lymphatic endothelial cells in vivo and in vitro. Mechanistically, LIPAR linked ITGA6 to the switch II domain of RAB5A and sustained RAB5A GTP-bound activated state, thus maintaining the production of ITGA6+EVs loaded with LIPAR through endosomal trafficking. ITGA6+EVs targeted lymphatic vessels through ITGA6-CD151 interplay and released LIPAR to induce SELE overexpression-marked lymphatic remodelling pre-metastatic niche. Importantly, we constructed engineered-ITGA6 EVs to inhibit lymphatic pre-metastatic niche, which suppressed lymphatic metastasis and prolonged survival in preclinical models. Collectively, our study uncovers the mechanism of BCa-derived ITGA6+EVs mediating pre-metastatic niche and provides an engineered-EV-based strategy against BCa lymphatic metastasis.

Internship and postgraduate entrance examination: A qualitative study on the psychological experience of undergraduate nursing students under dual pressure in China.

Background: With the development of nursing positions and nursing disciplines in China's tertiary hospitals, the number of people applying for the master's degree in nursing is also increasing year by year. Postgraduate examinations are held during internship, so nursing students face the dual pressure of testing and internship, which brings varying degrees of negative experiences and emotional fluctuations. Objective: To explore the psychological experiences and influencing factors of undergraduate nursing students under the dual pressures of clinical nursing internships and postgraduate examination preparations. Design: Descriptive qualitative study. Method: Purposeful sampling was used to recruit 18 participants from eight tertiary hospitals in China between October and December 2023. Semi-structured in-depth interviews were conducted, with interview recordings transcribed verbatim. Thematic analysis was then applied to the data. Results: Four themes were identified: negative experiences under dual pressures, coping mechanisms for negative experiences, motivational effects under dual pressures, and evaluations of significant individuals. Nursing students improved their overall abilities through internships and exam preparations, gaining a clear understanding of themselves and certain hospital roles. However, at this stage, students also experienced adverse psychological experiences for various reasons. Thus, they employed several methods to alleviate their psychological stress, aiming for a better state to face internships and exam preparations. Conclusion: Schools and hospitals should pay more attention to the needs of nursing students under dual pressures, monitoring their emotional states, and providing psychological support to enhance their stress-coping abilities. It is important to ensure the overall well-being of students while strengthening the motivational effects of internships and learning experiences.

Theoretical study on multi-perspective interaction analysis of ADN and ADN-H2O-CH3OH solutions.

CONTEXT: Revealing the mechanism of intermolecular interactions in dinitroamine ammonium (ADN)-based liquid propellants and exploring the reasons for their performance changes, multi-perspective interaction analyses of ADN and ADN-water (H2O)-methanol (CH3OH) solutions have been conducted via theoretical methods. The band structure, density of states (DOS), surface electrostatic potential (ESP), Hirshfeld surface, reduced density gradient (RDG), AIM topological analysis, and detonation performance were studied and the results showed that both the ADN and ADN-H2O-CH3OH solutions had hydrogen bonds and van der Waals interactions. By introducing the small molecules H2O and CH3OH, the detonation performance of the ADN-H2O-CH3OH solution slightly decreased, but its sensitivity also decreased. Overall, the comprehensive performance of the ADN-H2O-CH3OH solution has improved, and the application range has expanded. These results are helpful for obtaining a deeper understanding of ADN-based liquid propellants at the atomic level and contribute to the development of new liquid propellants. METHODS: The ADN and ADN-H2O-CH3OH solutions were constructed by Amorphous cell module and optimized via GGA with PBE methods in the Dmol3 module of the Materials Studio, and their electronic properties were calculated. Hirshfeld surfaces were generated with CrystalExplorer 3.0. A topological analysis of a variety of molecular clusters was performed via QTAIM. The QTAIM and RDG analyses in this work were generated by Multiwfn 3.0.

Principle and Logic of Vertical Reduction Repair Double-Ring Breast Reduction.

BACKGROUND: Secondary reduction mammaplasty poses challenges. OBJECTIVES: This article delves into the reasons and complaints regarding secondary repair following double-ring method and outlines the principle and logic of utilizing vertical incision for repair. METHODS: A retrospective analysis of patients who underwent secondary reduction mammaplasty in our hospital was conducted. The analysis included baseline demographic data, reasons for consultation, surgical records, and postoperative outcomes. RESULTS: Thirty-five patients (70 breasts) underwent secondary reduction mammaplasty. The mean time between the primary reduction mammaplasty and second procedure was 2.99 years (range, 0.5-15years). The mean weights were 210.49g (range, 42-558g) and 207.91g (range, 6-560g) for left and right mastectomies, respectively. Reasons for secondary reduction mammaplasty include poor shape (flat breasts and pseudoptosis), widened incision scar, persistent macromastia, and bilateral asymmetry. CONCLUSIONS: The superior and superomedial vertical techniques are safe, effective, and satisfactory in secondary reduction mammaplasty. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .

Carbohydrate-based block copolymers with sub-10 nm face-centered cubic nanostructures for low-power-consuming and ultraviolet light-triggered synaptic phototransistors.

Addressing environmental concerns and producing sustainable and environmentally friendly electronic devices with low power consumption poses a significant challenge. This study introduces phototransistor devices employing morphologically controlled block copolymers based on maltotriose, maltoheptaose, and ß-cyclodextrin as polymer electrets. Ordered self-assembled morphologies can be achieved by utilizing microwave radiation for rapid annealing (within 5 s) with optimized annealing conditions. Herein, face-centered cubic (FCC), vertical, and mixed cylindrical nanostructures are reported. The resulting well-defined morphologies play a pivotal role in enhancing the electron-trapping capability of the block copolymers and facilitating charge carrier transport between the electret and semiconducting layers. Consequently, the phototransistor memory manifests exceptional performance, featuring stability and endurance. Intriguingly, the cavity of ß-cyclodextrin provides a stable environment for the trapped charges, leading to a larger memory window than other block copolymers. On the other hand, a device consisting of MT-b-PS exhibited superior current contrast exceeding 106 even under a low drain voltage of -1 V, attributed to sub-10 nm FCC nanostructures. Furthermore, this phototransistor device successfully emulated the synaptic functions of sensing, learning, and short- and long-term memory in the human brain, along with a low energy consumption of 0.312 fJ. Hence, this report opens the pathways for developing promising bio-based electronic devices.

A prospective single arm cohort study: An analysis of the effectiveness of surgical treatment of locally advanced breast cancer.

Background: Breast cancer stands as a globally significant contributor to both incidence rates and mortality among women. Approximately 10-15 % of women will face a diagnosis of an advanced yet potentially treatable stage of the disease. When individuals diagnosed with locally advanced breast cancer (LABC) exhibit resistance to preoperative chemotherapy and experience tumor progression, they unfortunately forfeit the opportunity for surgical intervention, thereby diminishing the prospects for a radical cure. Method: We conducted a prospective, single-arm cohort study aimed at evaluating the feasibility of locally modified radical resection for LABC with skin invasion. The primary endpoints encompassed overall survival (OS) and disease-free survival (DFS), whereas the secondary endpoint focused on the quality of life (QoL) among breast cancer patients. Results: Between March 2018 and December 2022, a total of 38 eligible patients were enrolled in this study. The Kaplan-Meier estimates for 1-year, 3-year, and 5-year DFS among all patients were 69.8 %, 53.3 %, and 37.5 %, respectively. Correspondingly, the OS rates were 100.0 %, 85.6 %, and 68.0 %. Both univariate and multivariate analyses revealed that patients with a history of neoadjuvant chemotherapy who exhibited stable or progressive disease had inferior DFS outcomes. Notably, patients demonstrated clinically meaningful and statistically significant enhancements in functional status and overall QoL. However, no notable improvement was observed in specific symptom domains. Conclusion: Patients with locally advanced breast cancer, specifically those presenting with T4 tumors, who undergo surgical intervention followed by postoperative adjuvant therapy, can attain favorable prognostic outcomes and experience an enhanced quality of life.

Submucosal cystic adenomyosis: a report of five cases and review of the literature.

AIM: To investigate the clinical characteristics, diagnosis, and clinical treatment of submucosal cystic adenomyosis. METHODS: The clinical data of five cases of patients with submucosal cystic adenomyosis in our hospital from January 2020 to June 2023 were retrospectively analyzed. RESULTS: The average age of the patients was 37.8 ± 4.5 years old, three of them experienced prolonged menstruation and heavy menstrual bleeding. All patients had a history of abnormal uterine bleeding and mild to moderate dysmenorrhea, with a VAS score of 2.8 ± 1.6. The average Carbohydrate antigen 125 (CA125) value was 29.9 ± 23.6U/ml. Two out of the five patients (40%) had CA125 values above the upper limit of normal. The nodules had a diameter of 3.2 ± 1.3 cm and a cavity size of 1.3 ± 0.7 cm. Color ultrasound revealed hypo or iso or anechoic echoic cysts, and blood flow signals were detected. The magnetic resonance imaging (MRI) findings varied among each patient. All the patients underwent hysteroscopy and resection of uterine cavity-occupying lesions, and no recurrence was observed. CONCLUSIONS: The clinical features of submucosal cystic adenomyosis include abnormal uterine bleeding and menstrual changes, and the degree of dysmenorrhea is generally not severe. The diagnostic utility of CA125 in submucosal cystic adenomyosis may be limited. The three-dimensional ultrasound and MRI are valuable preoperative examination methods currently. Hysteroscopy can not only diagnose submucosal cystic adenomyosis, but also treat it, and preserve the fertility function of the patient.

Smoking cessation to prevent death and tuberculosis recurrence after treatment: A prospective cohort study with a seven-year follow-up in China.

Background: Although there is consistent evidence that smoking is a risk factor associated with tuberculosis (TB), whether smoking cessation improves treatment outcomes and reduces the risk of TB recurrence remains understudied. Methods: We conducted a prospective cohort study with a seven-year follow-up in China. We recruited newly-diagnosed TB patients and classified them as non-smokers, ex-smokers, and current smokers. Current smokers were invited to participate in a smoking cessation intervention programme. We used a Cox proportional hazards model to assess the risk of death among TB patients and the risk of recurrence among successfully treated patients. Results: In total, 634 (79.2%) patients completed anti-TB treatments and 115 (14.4%) patients died. We confirmed the existence of a dose-response relationship between smoking frequency and the risk of TB recurrence (the slope of the fitted line >0; P < 0.05). Compared to those who continued smoking, the risk of death and recurrent TB for the patients who quit smoking during treatment decreased. The HR of mortality for smokers who smoked 30 or more cigarettes was 2.943 (95% confidence interval (CI) = 1.035-8.368), while the HR of mortality for those who smoked 30 or more cigarettes, but quit during treatment was 2.117 (95% CI = 1.157-3.871). However, the risk of recurrence remained high for ex-smokers who had a smoking history of 25 years or more. Conclusions: Our study provides further evidence supporting the World Health Organization's call for co-management of smoking and other risk factors as part of routine TB treatment.

Inferior spikelet filling is affected by T6P/SnRK1-mediated NSC remobilization in large-panicle rice (Oryza sativa L.).

Poor grain filling in inferior spikelets (IS), which is influenced by the remobilization of nonstructural carbohydrates (NSC) stored in the sheath and internode of rice plants, limits the expected high yield of large-panicle rice. NSC remobilization from the sheath to the panicle is regulated by the T6P/SnRK1 pathway. However, in large-panicle rice, it is unclear whether IS grain filling is related to the NSC remobilization mediated by T6P/SnRK1 signaling. In this study, two large-panicle cultivars-W1844 and CJ03-with distinct differences in IS grain filling were used to explore the physiological mechanism mediating IS development. Compared to W1844, CJ03 IS showed lower expression of the genes related to sucrose uploading, later sucrose peaking, and delayed starch accumulation. In the CJ03, low OsSUTs expression and NSC output, transport rate, and contribution rate were detected in the sheaths and internodes. These results suggest that poor NSC remobilization results in insufficient assimilate supply for the IS, and consequently, poor IS grain filling. Furthermore, poor NSC remobilization coincided with the increased T6P content and decreased SnRK1 activity during grain filling in CJ03 IS. The expression levels of genes related to T6P metabolism and those encoding the catalytic subunit of SnRK1 were consistent with the observed T6P content and SnRK1 activity in the sheaths and internodes. Therefore, IS grain filling is potentially affected by T6P/SnRK1 signaling-mediated NSC remobilization in large-panicle rice.

Optimizing treatment sequence for inoperable locally advanced breast cancer: Long-term outcomes of surgery first versus neoadjuvant chemotherapy in a real-world setting.

Locally advanced breast cancer (LABC) is challenging with limited treatment options. This study investigates the feasibility and long-term outcomes of upfront surgery compared to neoadjuvant chemotherapy (NAC) in a real-world cohort. This retrospective study analyzed 243 inoperable LABC patients (excluding T3N1M0) that underwent upfront surgery (n = 187) or NAC (n = 56) in matched groups. Disease-free survival (DFS) and overall survival (OS) are primary outcomes. Secondary outcomes included NAC response rate and subgroup analyses based on age, tumor stage, and treatment response. Survival was estimated using Kaplan-Meier methods with log-rank tests for comparisons. Cox proportional hazards models were used for subgroup analyses. With a median follow-up of 60.9 months, no significant difference emerged in 5-year OS (upfront surgery: 89.6%, NAC: 81.9%, p = .12) or 5-year DFS rates (73.0% vs. 67.1%, p = .24). Subgroup analyses revealed upfront surgery offered significantly better OS for patients under 60 (HR = 0.32; 95% CI: 0.10-0.96; p = .0429) and stage IIIA disease (HR = 0.22; CI: 0.06-0.86; p = .03). Upfront surgery showed a trend towards improved OS for tumors under 5 cm (HR = 0.37; 95% CI: 0.13-1.03; p = .056). Patients with progressive disease (PD) or stable disease (SD) after NAC had significantly worse DFS (HR = 0.27; 95% CI: 0.09-0.79; p = .017) and OS (HR = 0.09; 95% CI: 0.02-0.48; p = .004) compared to responders. Upfront surgery may be viable for LABC patients, particularly younger patients, those with stage IIIA disease, or smaller tumors. NAC response can inform treatment decisions. These findings highlight the need for personalized LABC treatment considering patient characteristics and NAC response.