Photocatalytic Generation of Carbocation from Thiols and Application to Cross-Nucleophile Coupling.

Represented herein is a simple thiol identified as an effective precursor to photochemically form a carbocation. Thanks to the thiyl radical rapid transformation to disulfide, which serves not only to stabilize the generated thiyl radical but also to allow the second electron transfer to form a carbocation. The resulting carbocations, including primary benzylic, secondary, and tertiary carbocations, can smoothly couple with nitrogen, oxygen, and carbon nucleophilic coupling partners as well as complex drug molecules, accompanied by elemental sulfur formation in air.

The complete plastome and phylogenetic analysis of Commelina benghalensis L.1753 (Commelinaceae).

Commelina benghalensis L. 1753, a member of the Commelinaceae family, holds significant medicinal and culinary value. This study represents the first documentation of the sequencing and assembly of the entire plastome of C. benghalensis. The genome spans a total length of 160,663 bp, exhibiting a conventional quadripartite architecture that comprises a large single-copy (LSC) region (87,750 bp), a small single-copy (SSC) region (18,417 bp), and two inverted repeats (IR) regions (both 27,248 bp). In its entirety, the C. benghalensis plastome encompasses 129 genes (with 108 being unique), incorporating 77 individual protein-coding genes, 37 unique tRNA genes, and four unique rRNA genes. Phylogenetic analysis revealed a close resemblance between C. benghalensis and C. communis. The sequencing of this plastome stands to expedite the development of molecular markers and significantly contribute to genetic assays involving this distinctive plant.

Clinical and economic outcomes associated with lymph node examination status in early-stage non-small cell lung cancer: a real-world US study using the SEER-Medicare linked database.

Background: Clinical practice guidelines recommend adjuvant therapy for patients with early non-small cell lung cancer (eNSCLC), especially those with lymph node metastasis. This study evaluated the prevalence of lymph node examination and its association with adjuvant treatment rates, overall survival (OS), and healthcare costs among United States (US) Medicare patients with resected eNSCLC. Methods: This retrospective observational cohort study used Surveillance, Epidemiology, and End Results cancer registry data linked with Medicare claims data. Eligible patients were aged ≥65 years with newly diagnosed non-small cell lung cancer (NSCLC) stages IA to IIIB [the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 7th edition] between January 2010 and December 2017 with surgery ≤1 month prior to or ≤12 months after diagnosis. Patients were grouped by lymph node examination status: no examination (pNX), examination and no metastasis (pN0), or metastasis staging in N1 (pN1) or N2 (pN2). OS and costs were evaluated by examination status and number of lymph node examined. OS was analyzed using extended Cox proportional hazards models for specific time periods and time interaction with examination status, and adjusted for patient characteristics. Adjusted post-surgical healthcare costs per patient per month (PPPM) were analyzed using gamma-log regression models. Results: Among the 14,648 patients included in the study, approximately 11% were pNX, whereas most were pN0 (68%), followed by pN1 (11%) and pN2 (10%). Adjuvant treatment rates were higher for pNX (35%) than pN0 (18%), but lower than pN1 (68%) and pN2 (74%) patients (P<0.001). Unadjusted OS for pNX patients was nearly identical to pN2, and significantly worse compared to pN0 and pN1 (P<0.0001). After adjusting for patient characteristics, pNX patients had higher risk of death relative to pN0 patients (P<0.001). Marginal mean adjusted total costs were comparable across pNX ($15,827 PPPM), pN0 ($12,712 PPPM) and pN1 ($17,089 PPPM), but significantly less for pN0 compared to pN2 ($23,566 PPPM) (P=0.002). Conclusions: Inadequate lymph node examination is associated with underutilization of adjuvant treatment and poor OS in resected NSCLC. In the current era of targeted and immunotherapies, lymph node examination is more important than ever, implicating the need for Quality Improvement practices and multidisciplinary coordination.

Evaluation of the tumor-targeting specific imaging and killing effect of a CEA-targeting nanoparticle in colorectal cancer.

INTRODUCTION: Colorectal cancer (CRC) is a prevalent digestive malignancy with significant global mortality and morbidity rates. Improving diagnostic capabilities for CRC and investigating novel therapeutic approaches are pressing clinical imperatives. Additionally, carcinoembryonic antigen (CEA) has emerged as a highly promising candidate for both colorectal tumor imaging and treatment. METHODS: A novel active CEA-targeting nanoparticle, CEA(Ab)-MSNs-ICG-Pt, was designed and synthesized, which served as a tumor-specific fluorescence agent to help in CRC near-infrared (NIR) fluorescence imaging. In cell studies, CEA(Ab)-MSNs-ICG-Pt exhibited specific targeting to RKO cells through specific antibody-antigen binding of CEA, resulting in distribution both within and around these cells. The tumor-targeting-specific imaging capabilities of the nanoparticle were determined through in vivo fluorescence imaging experiments. Furthermore, the efficacy of the nanoparticle in delivering chemotherapeutics and its killing effect were evaluated both in vitro and in vivo. RESULTS: The CEA(Ab)-MSNs-ICG-Pt nanoparticle, designed as a novel targeting agent for carcinoembryonic antigen (CEA), exhibited dual functionality as a targeting fluorescent agent. This CEA-targeting nanoparticle showed exceptional efficacy in eradicating CRC cells in comparison to individual treatment modalities. Furthermore, it exhibits exceptional biosafety and biocompatibility properties. CEA(Ab)-MSNs-ICG-Pt exhibits significant promise due to its ability to selectively target tumors through NIR fluorescence imaging and effectively eradicate CRC cells with minimal adverse effects in both laboratory and in vivo environments. CONCLUSION: The favorable characteristics of CEA(Ab)-MSNs-ICG-Pt offer opportunities for its application in chemotherapeutic interventions, tumor-specific NIR fluorescence imaging, and fluorescence-guided surgical procedures.

Effect of the Activation Force of Mechanophore on Its Activation Selectivity and Efficiency in Polymer Networks.

In recent decades, more than 100 different mechanophores with a broad range of activation forces have been developed. For various applications of mechanophores in polymer materials, it is crucial to selectively activate the mechanophores with high efficiency, avoiding nonspecific bond scission of the material. In this study, we embedded cyclobutane-based mechanophore cross-linkers (I and II) with varied activation forces (fa) in the first network of the double network hydrogels and quantitively investigated the activation selectivity and efficiency of these mechanophores. Our findings revealed that cross-linker I, with a lower activation force relative to the bonds in the polymer main chain (fa-I/fa-chain = 0.8 nN/3.4 nN), achieved efficient activation with 100% selectivity. Conversely, an increase of the activation force of mechanophore II (fa-II/fa-chain = 2.5 nN/3.4 nN) led to a significant decrease of its activation efficiency, accompanied by a substantial number of nonspecific bond scission events. Furthermore, with the coexistence of two cross-linkers, significantly different activation forces resulted in the almost complete suppression of the higher-force one (i.e., I and III, fa-I/fa-III = 0.8 nN/3.4 nN), while similar activation forces led to simultaneous activations with moderate efficiencies (i.e., I and IV, fa-I/fa-IV = 0.8 nN/1.6 nN). These findings provide insights into the prevention of nonspecific bond rupture during mechanophore activation and enhance our understanding of the damage mechanism within polymer networks when using mechanophores as detectors. Besides, it establishes a principle for combining different mechanophores to design multiple mechanoresponsive functional materials.

Association between pretreatment emotional distress and immune checkpoint inhibitor response in non-small-cell lung cancer.

Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979 .

Enhanced Aggregation-Induced Delayed Electrochemiluminescence Triggered by Spatial Perturbation of Organic Dots.

Development of highly efficient, heavy-metal-free electrochemiluminescence (ECL) materials is attractive but still challenging. Herein, we report an aggregation-induced delayed ECL (AIDECL) active organic dot (OD) composed of a tert-butoxy-group-substituted benzophenone-dimethylacridine compound, which shows high ECL efficiency. The resultant ODs exhibit 2.1-fold higher ECL efficiency compared to control AIDECL-active ODs. Molecular stacking combined with theoretical calculations suggests that tert-butoxy groups effectively participate in the intermolecular interactions, further inhibiting the molecular motions in the aggregated states and thus accelerating radiative decay. On the basis of these ODs exhibiting excellent ECL performance, a proof-of-concept biosensor is constructed for the detection of miR-16 associated with Alzheimer's disease, which demonstrates excellent detection ability with the limit of detection of 1.7 fM. This work provides a new approach to improve the ECL efficiency and enriches the fundamental understanding of the structure-property relationship.

Multicolor Inks of Black Phosphorus for Midwave-Infrared Optoelectronics.

Black phosphorus (bP) based ink with a bulk bandgap of 0.33 eV (λ = 3.7 µm) has recently been shown to be promising for large-area, high performance mid-wave infrared (MWIR) optoelectronics. However, the development of multicolor bP inks expanding across the MWIR wavelength range has been challenging. Here we demonstrate a multicolor ink process based on bP with spectral emission tuned from 0.28 eV (λ ∼ 4.4 µm) to 0.8 eV (λ ∼ 1.5 µm). Specifically, through the reduction of bP particle size distribution (i.e., lateral dimension and thickness), the optical bandgap systematically blue-shifts, reaching up to 0.8 eV. Conversely, alloying bP with arsenic (bP1- xAsx) induces a red-shift in the bandgap to 0.28 eV. The ink processed films are passivated with an infrared-transparent epoxy for stable infrared emission in ambient air. Utilizing these multicolor bP-based inks as an infrared light source, a gas sensing system is demonstrated that selectively detects gases such as CO2 and CH4 whose absorption band varies around 4.3 µm and 3.3 µm, respectively. The presented ink formulation sets the stage for the advancement of multiplex MWIR optoelectronics, including spectrometers and spectral imaging using a low-cost material processing platform. This article is protected by copyright. All rights reserved.

Mechanism of efferocytosis in atherosclerosis.

Atherosclerosis (AS) is a chronic inflammatory vascular disease that occurs in the intima of large and medium-sized arteries with the immune system's involvement. It is a common pathological basis for high morbidity and mortality of cardiovascular diseases. Abnormal proliferation of apoptotic cells and necrotic cells leads to AS plaque expansion, necrotic core formation, and rupture. In the early stage of AS, macrophages exert an efferocytosis effect to engulf and degrade apoptotic, dead, damaged, or senescent cells by efferocytosis, thus enabling the regulation of the organism. In the early stage of AS, macrophages rely on this effect to slow down the process of AS. However, in the advanced stage of AS, the efferocytosis of macrophages within the plaque is impaired, which leads to the inability of macrophages to promptly remove the apoptotic cells (ACs) from the organism promptly, causing exacerbation of AS. Moreover, upregulation of CD47 expression in AS plaques also protects ACs from phagocytosis by macrophages, resulting in a large amount of residual ACs in the plaque, further expanding the necrotic core. In this review, we discussed the molecular mechanisms involved in the process of efferocytosis and how efferocytosis is impaired and regulated during AS, hoping to provide new insights for treating AS.

Do we need reshape rTNM staging system for ipsilateral breast tumor recurrence of breast cancer? A population-based, propensity score matched cohort study.

BACKGROUND: The aim of the study was to explore the role of recurrent TNM (rTNM) staging in predicting prognosis for ipsilateral breast tumor recurrence (IBTR) and determine the optimal treatment strategy for IBTR. METHOD: IBTR cases were identified from the Surveillance, Epidemiology, and End Results (SEER) database spanning the years 2000-2018. Cox proportional hazards analysis was performed to examine factors associated with overall survival (OS) and breast cancer-specific survival (BCSS). Propensity score matching (PSM) was employed to match IBTR with primary early breast cancer (EBC) based on clinicopathological characteristics. Investigations into the impact of different therapies were also included. RESULTS: Of the 4375 IBTR cases included in the study, the 5-year OS was 87.1%, 71.6% and 58.7% in rTNM stages I, II and III, respectively. After PSM, while IBTR patients had worse survival to primary EBC patients, prognosis of IBTR for different rTNM stage always closely aligned with the corresponding stage of primary EBC. Repeat breast-conserving surgery (BCS) with radiation therapy was equivalent to mastectomy with respect to OS and BCSS. Chemotherapy was favorable for OS and BCSS in estrogen receptor (ER)-negative IBTR or IBTR occurring within a 60-month interval. CONCLUSIONS: rTNM staging system has an outstanding prognostic value for survival outcome of patients with IBTR, and IBTR and primary EBC may have potentially analogous features in the context of TNM staging. BCS plus radiation therapy may be an alternative. IBTR cases who have experienced recurrence with short intervals and with ER-negative tumors might benefit from chemotherapy.

Preoperative chemoradiotherapy in older patients with rectal cancer guided by comprehensive geriatric assessment within a multidisciplinary team-a multicenter phase II trial.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of preoperative concurrent chemoradiotherapy (preCRT) for locally advanced rectal cancer in older people who were classified as "fit" by comprehensive geriatric assessment (CGA). METHODS: A single-arm, multicenter, phase II trial was designed. Patients were eligible for this study if they were aged 70 years or above and met the standards of "fit" (SIOG1) as evaluated by CGA and of the locally advanced risk category. The primary endpoint was 2-year disease-free survival (DFS). Patients were scheduled to receive preCRT (50 Gy) with raltitrexed (3 mg/m2 on days 1 and 22). RESULTS: One hundred and nine patients were evaluated by CGA, of whom eighty-six, eleven and twelve were classified into the fit, intermediate and frail category. Sixty-eight fit patients with a median age of 74 years were enrolled. Sixty-four patients (94.1%) finished radiotherapy without dose reduction. Fifty-four (79.3%) patients finished the prescribed raltitrexed therapy as planned. Serious toxicity (grade 3 or above) was observed in twenty-four patients (35.3%), and fourteen patients (20.6%) experienced non-hematological side effects. Within a median follow-up time of 36.0 months (range: 5.9-63.1 months), the 2-year overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) rates were 89.6% (95% CI: 82.3-96.9), 92.4% (95% CI: 85.9-98.9) and 75.6% (95% CI: 65.2-86.0), respectively. Forty-eight patients (70.6%) underwent surgery (R0 resection 95.8%, R1 resection 4.2%), the corresponding R0 resection rate among the patients with positive mesorectal fascia status was 76.6% (36/47). CONCLUSION: This phase II trial suggests that preCRT is efficient with tolerable toxicities in older rectal cancer patients who were evaluated as fit based on CGA. TRIAL REGISTRATION: The registration number on ClinicalTrials.gov was NCT02992886 (14/12/2016).

Narrative review on advancing breast cancer treatment: harnessing the power of PD-1/PD-L1 inhibitors for improved patient outcomes.

Background and Objective: Cancer immunotherapy has significantly advanced the field of oncology, providing novel therapeutic strategies for various malignancies, including breast cancer. The programmed cell death protein 1/programmed cell death-ligand 1 (PD-1/PD-L1) pathway is pivotal in immune regulation, and its inhibitors have demonstrated therapeutic benefits in diverse tumors. This review aims to critically examine the role, clinical efficacy, safety, and future directions of PD-1/PD-L1 inhibitors in breast cancer treatment, with a focus on pembrolizumab, nivolumab, and tislelizumab, and to elucidate the challenges and prospects in this dynamic field. Methods: A comprehensive literature search was conducted, adhering to Narrative Review reporting checklist for transparent reporting. Data from selected studies were qualitatively analyzed to synthesize key findings related to the mechanisms of action, clinical applications, and challenges of PD-1/PD-L1 inhibitors in breast cancer. Key Content and Findings: PD-1 inhibitors have shown remarkable efficacy in various malignancies, including advanced triple-negative breast cancer (TNBC), where they have been investigated both in combination with chemotherapy and as neoadjuvant/adjuvant treatment. The exploration of these inhibitors in other breast cancer subtypes, such as human epidermal growth factor receptor-positive and hormone receptor-positive breast cancer, is ongoing. The review highlights the challenges in patient selection, management of immune-related adverse events (irAEs), and the emergence of resistance mechanisms. It underscores the need for ongoing research focusing on identifying reliable predictive biomarkers, elucidating mechanisms of resistance, and optimizing treatment strategies. Conclusions: PD-1/PD-L1 inhibitors hold substantial promise in advancing breast cancer treatment. This review provides critical insights and emphasizes the clinical importance of continued scientific exploration to refine patient selection criteria, improve treatment outcomes, and expand the applications of immunotherapy in breast cancer. Further research is imperative to overcome the existing challenges and realize the full therapeutic potential of these inhibitors in breast cancer and other malignancies.

Potential rapid intraoperative cancer diagnosis using dynamic full-field optical coherence tomography and deep learning: A prospective cohort study in breast cancer patients.

An intraoperative diagnosis is critical for precise cancer surgery. However, traditional intraoperative assessments based on hematoxylin and eosin (H&E) histology, such as frozen section, are time-, resource-, and labor-intensive, and involve specimen-consuming concerns. Here, we report a near-real-time automated cancer diagnosis workflow for breast cancer that combines dynamic full-field optical coherence tomography (D-FFOCT), a label-free optical imaging method, and deep learning for bedside tumor diagnosis during surgery. To classify the benign and malignant breast tissues, we conducted a prospective cohort trial. In the modeling group (n = 182), D-FFOCT images were captured from April 26 to June 20, 2018, encompassing 48 benign lesions, 114 invasive ductal carcinoma (IDC), 10 invasive lobular carcinoma, 4 ductal carcinoma in situ (DCIS), and 6 rare tumors. Deep learning model was built up and fine-tuned in 10,357 D-FFOCT patches. Subsequently, from June 22 to August 17, 2018, independent tests (n = 42) were conducted on 10 benign lesions, 29 IDC, 1 DCIS, and 2 rare tumors. The model yielded excellent performance, with an accuracy of 97.62%, sensitivity of 96.88% and specificity of 100%; only one IDC was misclassified. Meanwhile, the acquisition of the D-FFOCT images was non-destructive and did not require any tissue preparation or staining procedures. In the simulated intraoperative margin evaluation procedure, the time required for our novel workflow (approximately 3 min) was significantly shorter than that required for traditional procedures (approximately 30 min). These findings indicate that the combination of D-FFOCT and deep learning algorithms can streamline intraoperative cancer diagnosis independently of traditional pathology laboratory procedures.

Influence of administration timing of San-Huang-Xie-Xin-Tang treatment on attenuating Salmonella enterica serovar Typhimurium infection.

Salmonella infections are a serious global health concern, particularly in developing countries, and are further exacerbated by the emergence of antibiotic resistance. San-Huang-Xie-Xin-Tang (SHXXT), a traditional herbal medicine with potent anti-inflammatory properties, has recently gained attention as an alternative treatment. Our study emphasizes on the importance of precise timing in accordance with traditional Chinese medicine principles. A mouse infection model was established while different administration times of SHXXT were recorded for the body weight, clinical scores, bacterial counts in blood, and organs. Additionally, cytokine levels, fatty acids, and amino acids in the serum were also monitored. We found that administering SHXXT 1 day after Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) infection (T1 group) leads to positive outcomes. This includes restoration of body weight, improved clinical scores, and reduced bacterial counts in blood and vital organs. Interferon-gamma levels remained consistently high across all treatment groups 6 days post-infection. However, the T1 group showed exclusive suppression of serum levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß). The timing of administration significantly influenced serum fatty acid concentrations, countering Salmonella-induced disruptions, aligning with TNF-α and IL-1ß levels. SHXXT had also restored amino acid profiles disrupted by the infection, with notable effects when administered at the correct timing. Our research highlights SHXXT's potential in treating S. Typhimurium infection, emphasizing the importance of precise timing in line with traditional Chinese medicine principles for effective treatment at different disease stages.

Intraoperative transcutaneous electroacupoint stimulation on early postoperative fatigue in patients with Parkinson's disease undergoing deep brain stimulation surgery.

Background: In this clinical trial, we evaluated the effects of transcutaneous electroacupoint stimulation (TEAS) on postoperative fatigue (POF) in Parkinson disease (PD) patients undergoing deep brain stimulation (DBS) surgery. Methods: A total 60 PD patients undergoing DBS surgery were enrolled. They were randomized to receive either electrical stimulation [alternative frequency 2/10 Hz, dense and disperse, intensity adjusted to the maximum tolerated by the participants (6-15 mAmp)] via surface electrodes (TEAS group) or surface electrodes only without electrical stimulation (Con group) at bilateral Zusanli and Sanyinjiao acupuncture points. All participants received their assigned intervention (TEAS or Con) during the 1st stage of surgery [(except during microelectrode recording (MER)] and the entire 2nd stage of surgery. Intraoperative anesthetic requirements were adjusted based on bispectral index (BIS) monitor. POF was assessed by Christensen fatigue scales (ChrFS), along with Quality of Recovery-15 (QoR-15) and mini-mental state examination (MMSE) postoperatively over a 7-day-period. We recorded the usage of rescue analgesics and anti-emetics. Results: Fifty-nine patients' datasets were included for final analyses. Fewer patients in TEAS experienced severe POF (defined as ChrFS ≥6) at T3 than those in the Con group (TEAS vs. Con: 7 vs. 22, p < 0.001). During the 1st stage of surgery, more patients in Con group required dexmedetomidine infusion (TEAS vs. Con: 2 vs. 6; P < 0.01). Total dosages of propofol and remifanil during the 2nd stage of surgery were TEAS vs. Con: 374.7 ± 61.2 vs 421.5 ± 81.9; p < 0.001 and 572.3 ± 82.0 vs. 662 ± 148.2; P < 0.001, respectively. Postoperative rescue analgesics (TEAS vs. Con: 2 vs. 6; P < 0.001) were used less in the TEAS group. TEAS patients reported better POF, MMSE and QoR15 scores than those in the Con group during most of the assessment period. Conclusions: Intraoperative TEAS decreased the severity of POF, reduced intraoperative anesthetic requirements and facilitated post-DBS recovery in this group of PD patients.

Enhancing breast cancer outcomes with machine learning-driven glutamine metabolic reprogramming signature.

Background: This study aims to identify precise biomarkers for breast cancer to improve patient outcomes, addressing the limitations of traditional staging in predicting treatment responses. Methods: Our analysis encompassed data from over 7,000 breast cancer patients across 14 datasets, which included in-house clinical data and single-cell data from 8 patients (totaling 43,766 cells). We utilized an integrative approach, applying 10 machine learning algorithms in 54 unique combinations to analyze 100 existing breast cancer signatures. Immunohistochemistry assays were performed for empirical validation. The study also investigated potential immunotherapies and chemotherapies. Results: Our research identified five consistent glutamine metabolic reprogramming (GMR)-related genes from multi-center cohorts, forming the foundation of a novel GMR-model. This model demonstrated superior accuracy in predicting recurrence and mortality risks compared to existing clinical and molecular features. Patients classified as high-risk by the model exhibited poorer outcomes. IHC validation in 30 patients reinforced these findings, suggesting the model's broad applicability. Intriguingly, the model indicates a differential therapeutic response: low-risk patients may benefit more from immunotherapy, whereas high-risk patients showed sensitivity to specific chemotherapies like BI-2536 and ispinesib. Conclusions: The GMR-model marks a significant leap forward in breast cancer prognosis and the personalization of treatment strategies, offering vital insights for the effective management of diverse breast cancer patient populations.

Angiopoietin-like protein 4 induces growth hormone variant secretion and aggravates insulin resistance during pregnancy, linking obesity to gestational diabetes mellitus.

Angiopoietin-like protein 4 (ANGPTL4) is a secretory glycoprotein involved in regulating glucose homeostasis in non-pregnant subjects. However, its role in glucose metabolism during pregnancy and the pathophysiology of gestational diabetes mellitus (GDM) remains elusive. Thus, this study aimed to clarify the relationship between ANGPTL4 and GDM and investigate the pathophysiology of placental ANGPTL4 in glucose metabolism. We investigated this issue using blood and placenta samples in 957 pregnant women, the human 3A-sub-E trophoblast cell line, and the L6 skeletal muscle cell line. We found that ANGPTL4 expression in the placenta was higher in obese pregnant women than in lean controls. Palmitic acid significantly induced ANGPTL4 expression in trophoblast cells in a dose-response manner. ANGPTL4 overexpression in trophoblast cells resulted in endoplasmic reticulum (ER) stress, which stimulated the expression and secretion of growth hormone-variant (GH2) but not human placental lactogen. In L6 skeletal muscle cells, soluble ANGPTL4 suppressed insulin-mediated glucose uptake through the epidermal growth factor receptor (EGFR)/extracellular signal-regulated kinases 1/2 (ERK 1/2) pathways. In pregnant women, plasma ANGPTL4 concentrations in the first trimester predicted the incidence of GDM and were positively associated with BMI, plasma triglyceride, and plasma GH2 in the first trimester. However, they were negatively associated with insulin sensitivity index ISI0,120 in the second trimester. Overall, placental ANGPTL4 is induced by obesity and is involved in the pathophysiology of GDM via the induction of ER stress and GH2 secretion. Soluble ANGPTL4 can lead to insulin resistance in skeletal muscle cells and is an early biomarker for predicting GDM.

Cevanine-type steroidal alkaloids from the bulbs of Fritillaria cirrhosa D. Don.

Eight previously undescribed cevanine-type steroidal alkaloids, cirrhosinones I-N and cirrhosinols A-B, along with five known analogs, were isolated from the bulbs of Fritillaria cirrhosa D. Don. Their structures were elucidated on the basis of comprehensive analysis of HRESIMS, 1D and 2D NMR spectroscopic data, and single-crystal X-ray diffraction analyses. All compounds revealed weak NO inhibitory activities in the LPS-stimulated NR8383 cells at the concentration of 20 µM, with inhibition ratios ranging from 5.1% to 14.3%.

Dissolved oxygen facilitates efficiency of chlorine disinfection for antibiotic resistance.

Controlling the dissemination of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) is a global concern. While commonly used chlorine disinfectants can damage or even kill ARB, dissolved oxygen (DO) may affect the formation of reactive chlorine species. This leads to the hypothesis that DO may play roles in mediating the effectiveness of chlorine disinfection for antibiotic resistance. To this end, this study investigated the impacts of DO on the efficiency of chlorine disinfection for antibiotic resistance. The results revealed that DO could increase the inactivation efficiency of ARB under chloramine and free chlorine exposure at practically relevant concentrations. Reactive species induced by DO, including H2O2, O2-, and OH, inactivated ARB strains by triggering oxidative stress response and cell membrane damage. In addition, the removal efficiency of extracellular ARGs (i.e. tetA and blaTEM) was enhanced with increasing dosage of free chlorine or chloramine under aerobic conditions. DO facilitated the fragmentation of plasmids, contributing to the degradation of extracellular ARGs under exposure to chlorine disinfectants. The findings suggested that DO facilitates disinfection efficiency for antibiotic resistance in water treatment systems.

Callicarpayongshunensis (Lamiaceae): A new species from Hunan, China.

This study provides detailed description of a newly-discovered Callicarpayongshunensis Wen B. Xu, Xiao D. Li & Yan Ling Liu (Lamiaceae) species from Hunan, China. The species shares similarities in the inflorescence, glandular colour and leaf shape features with C.luteopunctata H. T. Chang and C.giraldii Hesse ex Rehd., while its white fruits are similar to those of C.longifolia Lamk. However, its procumbent, evergreen shrub and white fruits are distinctly different from those of C.luteopunctata and C.giraldii, while its procumbent, scarless nodes and stellate pubescence free fruits distinguishes it from C.longifolia. Images, distribution, morphological features, molecular phylogenetic classification and conservation assessment of this new Callicarpa species are explored.