Contezolid for the Treatment of Drug-Resistant Tuberculosis in China: A Clinical Case Series.

Background: Linezolid (LZD) is a cornerstone medication in the treatment of drug-resistant tuberculosis (DR-TB). However, it frequently triggers adverse effects such as bone marrow suppression, optic neuropathy, and peripheral neuropathy, all of which can impact treatment outcomes and prognosis. Contezolid (CZD), a novel oxazolidinone antibiotic, exhibits comparable antimicrobial efficacy against Mycobacterium tuberculosis as LZD, but with potentially enhanced safety profiles. Case Presentation: This report presents five cases (Cases 1-5) of LZD intolerance, wherein CZD served as an effective alternative treatment. In Cases 1-3, LZD administration resulted in bone marrow suppression, primarily manifested as anemia. Transitioning to CZD therapy led to a rise and stabilization of hemoglobin (HGB) levels in Cases 1-2, and a return to baseline values in Case 3. In Case 4, CZD treatment alleviated symptoms of LZD-induced peripheral neuritis, although complete resolution was not achieved, hinting at potential irreversibility of this type of peripheral neuropathy. In Case 5, direct CZD anti-TB therapy was initiated for recurrent leukopenia and neutropenia, resulting in no further severe myelosuppression and successful recovery. Conclusion: These case studies suggest that CZD could represent an effective and safe option for anti-TB therapy, especially for patients intolerant to LZD.

Optimal subsampling for semi-parametric accelerated failure time models with massive survival data using a rank-based approach.

Subsampling is a practical strategy for analyzing vast survival data, which are progressively encountered across diverse research domains. While the optimal subsampling method has been applied to inferences for Cox models and parametric accelerated failure time (AFT) models, its application to semi-parametric AFT models with rank-based estimation have received limited attention. The challenges arise from the non-smooth estimating function for regression coefficients and the seemingly zero contribution from censored observations in estimating functions in the commonly seen form. To address these challenges, we develop optimal subsampling probabilities for both event and censored observations by expressing the estimating functions through a well-defined stochastic process. Meanwhile, we apply an induced smoothing procedure to the non-smooth estimating functions. As the optimal subsampling probabilities depend on the unknown regression coefficients, we employ a two-step procedure to obtain a feasible estimation method. An additional benefit of the method is its ability to resolve the issue of underestimation of the variance when the subsample size approaches the full sample size. We validate the performance of our estimators through a simulation study and apply the methods to analyze the survival time of lymphoma patients in the surveillance, epidemiology, and end results program.

The protective effect of dulcitol on lipopolysaccharide-induced intestinal injury in piglets: mechanistic insights.

This study investigated the protective effect of dulcitol on LPS-induced intestinal injury in piglets and explored the underlying molecular mechanisms. A total of 108 piglets were divided into three groups: CON, LPS, and DUL. The CON and LPS groups were fed a basal diet, the DUL group was fed a diet supplementation with 500 mg/kg dulcitol. On day 29, 6 piglets in the LPS and DUL groups were injected with 100 µg/kg BW of LPS. At 4 h post-challenge, all pigs were slaughtered, and colonic samples were collected. Results showed that dulcitol supplementation boosted intestinal barrier function in LPS-challenged piglets by enhancing intestinal morphology and integrity, and increasing the gene expression of zonula occludens-1, claudin-1, and occludin in the colonic mucosa (P <0.05). Metabolomics showed DUL supplementation mainly increased (P <0.05) the metabolites related to steroid and vitamin metabolism (Cholesterol and Vitamin C). Proteomics showed that dulcitol supplementation altered the protein expression involved in maintaining barrier integrity (FN1, CADM1, and PARD3), inhibiting inflammatory response (SLP1, SFN, and IRF3), and apoptosis (including FAS, ING1, BTK, MTHFR, NOX, and P53BP2) in LPS-challenged piglets (P <0.05). Additionally, dulcitol addition also suppressed the TLR4/NF-κB signaling pathway and apoptosis in mRNA and protein levels. Dulcitol increased the abundance of short-chain fatty acid-producing bacteria (Lactobacillus, Blautia, and Faecalibacterium) at the genus level, but decreased the relative abundance of Proteobacteria at the phylum level and Pseudomonas and Delftia at the genus level in piglets (P < 0.05). In conclusion, these results suggested that the addition of dulcitol alleviated LPS-induced intestinal barrier injury in piglets, probably by maintaining its integrity, inhibiting the TLR4/NF-κB signaling pathways and apoptosis, and modulating the gut microbiota. Therefore, dulcitol can be considered a potential dietary additive for improving intestinal health in pig models.

DEAF-Net: Detail-Enhanced Attention Feature Fusion Network for Retinal Vessel Segmentation.

Retinal vessel segmentation is crucial for the diagnosis of ophthalmic and cardiovascular diseases. However, retinal vessels are densely and irregularly distributed, with many capillaries blending into the background, and exhibit low contrast. Moreover, the encoder-decoder-based network for retinal vessel segmentation suffers from irreversible loss of detailed features due to multiple encoding and decoding, leading to incorrect segmentation of the vessels. Meanwhile, the single-dimensional attention mechanisms possess limitations, neglecting the importance of multidimensional features. To solve these issues, in this paper, we propose a detail-enhanced attention feature fusion network (DEAF-Net) for retinal vessel segmentation. First, the detail-enhanced residual block (DERB) module is proposed to strengthen the capacity for detailed representation, ensuring that intricate features are efficiently maintained during the segmentation of delicate vessels. Second, the multidimensional collaborative attention encoder (MCAE) module is proposed to optimize the extraction of multidimensional information. Then, the dynamic decoder (DYD) module is introduced to preserve spatial information during the decoding process and reduce the information loss caused by upsampling operations. Finally, the proposed detail-enhanced feature fusion (DEFF) module composed of DERB, MCAE and DYD modules fuses feature maps from both encoding and decoding and achieves effective aggregation of multi-scale contextual information. The experiments conducted on the datasets of DRIVE, CHASEDB1, and STARE, achieving Sen of 0.8305, 0.8784, and 0.8654, and AUC of 0.9886, 0.9913, and 0.9911 on DRIVE, CHASEDB1, and STARE, respectively, demonstrate the performance of our proposed network, particularly in the segmentation of fine retinal vessels.

Highly Selective SO2 Capture by Triazine-Functionalized Triphenylamine-Based Nanoporous Organic Polymers.

The emissions of sulfur dioxide (SO2) from combustion exhaust gases pose significant risks to public health and the environment due to their harmful effects. Therefore, the development of highly efficient adsorbent polymers capable of capturing SO2 with high capacity and selectivity has emerged as a critical challenge in recent years. However, existing polymers often exhibit poor SO2/CO2 and SO2/N2 selectivity. Herein, we report two triazine-functionalized triphenylamine-based nanoporous organic polymers (ANOP-6 and ANOP-7) that demonstrate both good SO2 uptake and high SO2/CO2 and SO2/N2 selectivity. These polymers were synthesized through cost-effective Friedel-Crafts reactions using cyanuric chloride, 3,6-diphenylaminecarbazole, and 2,2',7,7'-tetrakis(diphenylamino)-9,9'-spirobifluorene. The resultant ANOPs are composed of triazine and triphenylamine units and feature an ultramicroporous structure. Remarkably, ANOPs exhibit impressive adsorption capacities for SO2, with uptakes of approximately 3.31-3.72 mmol·g-1 at 0.1 bar, increasing to 9.52-9.94 mmol·g-1 at 1 bar. The static adsorption isotherms effectively illustrate the ability of ANOPs to separate SO2 from SO2/CO2 and SO2/N2 mixtures. At 298 K and 1 bar, ANOP-6 shows outstanding selectivity toward SO2/CO2 (248) and SO2/N2 (13146), surpassing all previously reported triazine-based nanoporous organic polymers. Additionally, dynamic breakthrough tests demonstrate the superior separation properties of ANOPs for SO2 from an SO2/CO2/N2 mixture. ANOPs exhibit a breakthrough time of 73.1 min·g-1 and a saturated SO2 capacity of 0.53 mmol·g-1. These results highlight the exceptional adsorption properties of ANOPs for SO2, indicating their promising potential for the highly efficient capture of SO2 from flue gas.

Personality profiles and physical activity across adolescent: Based on latent profile analysis.

PURPOSE: Adolescent behavior is closely linked to personality, a key predictor of physical activity. Due to inconsistent findings on how personality dimensions influence physical activity, focusing on combinations of personality traits is more valuable for theoretical and practical guidance. This study aims to examine potential categories of adolescent personality and their relationship with physical activity. METHODS: Using data from the 2014-2015 China Education Panel Survey (CEPS), 9212 adolescents reported their "Big Five" personality and physical activity levels after excluding samples with missing core values. Latent profile analysis with Mplus 8.3 determined the optimal model by comparing model fits to categorize personality types. Bolck-Croon-Hagenaars (BHC) analysis was used to compared physical activity across personality profiles based on the resulting class differences and its significance. RESULTS: Latent profile analysis identified five personality trait types among adolescents based on fit indices such as AIC, BIC, aBIC, and Entropy: Low-control conservative group (5.0 %), Balanced development group (45.1 %), Optimistic action group (40.4 %), Independent avoidant group (4.5 %), and Introverted vulnerable group 5.0 %). Significant differences in physical activity were found among these profiles (p < 0.001), with individuals in the Optimistic action group tending to be more physically active and those in the Independent avoidance group being less physically active. CONCLUSION: Adolescent personality can be classified into five categories, and different combinations of personality traits can predict physical activity. The findings help identify adolescents who lack physical activity based on their personality profiles, allowing for the design of targeted psychological interventions to promote exercise motivation and foster healthy exercise habits. However, the study has limitations include a narrow age range and a single evaluation method. Future research could incorporate diverse evaluation methods and long-term tracking.

A case of primary cutaneous Cryptococcus neoformans infection.

BACKGROUND: Cryptococcosis is an infectious disease caused by encapsulated heterobasidiomycete yeasts. As an opportunistic pathogen, cryptococcal inhalation infection is the most common. While Primary cutaneous cryptococcosis is extremely uncommon. CASE PRESENTATION: A 61-year-old woman with a history of rheumatoid arthritis on long-term prednisone developed a red plaque on her left thigh. Despite initial antibiotic treatment, the erythema worsened, leading to rupture and fever. Microbiological analysis of the lesion's secretion revealed Candida albicans, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus epidermidis. Skin biopsy showed thick-walled spores, and culture confirmed primary cutaneous infection with Cryptococcus neoformans. Histopathological stains were positive, and mass spectrometry identified serotype A of the pathogen. The patient was treated with oral fluconazole and topical nystatin, resulting in significant improvement and near-complete healing of the skin lesion within 2.5 months. CONCLUSIONS: Primary cutaneous cryptococcosis was a primary skin infection exclusively located on the skin. It has no typical clinical manifestation of cutaneous infection of Cryptococcus, and culture and histopathology remain the gold standard for diagnosing. The recommended medication for Primary cutaneous cryptococcosis is fluconazole. When patients at risk for opportunistic infections develop skin ulcers that are unresponsive to antibiotic, the possibility of primary cutaneous cryptococcosis needs to be considered.

[Estimation of Regional Background Ozone in Henan Province from 2019 to 2021].

Clarifying the regional transmission and local generation contributions of ozone （O3） is important for controlling O3 pollution. To quantify the regional background and spatial-temporal variations of O3, a comprehensive study was conducted using multiple methods including principal component analysis （PCA） and TCEQ, with Henan Province as a case study. Based on monitoring data from 59 national sites in Henan Province during 2019-2021, four methods were employed to estimate the regional background of O3. Method 1 was the traditional method, performing O3 univariate-multisite PCA analysis. Method 2 was a multivariate-single-site PCA analysis considering nitrogen dioxide and meteorological conditions as constraints. Method 3 combined PCA and multiple linear regression （MLR） to determine regional background contributions, drawing on the idea of source apportionment. Method 4 was the TCEQ method that used the lowest measured O3-8h concentration as the regional background. The estimation results showed that Methods 1 and 2 were basically equal, and Methods 3 and 4 were approximately 37-60 µg·m-3 lower than Method 1. From 2019 to 2021, the changes in regional background ρ（O3-8h） estimated by Methods 1-4 were 1.6, -13.4, 5.9, and -3.5 µg·m-3, respectively. The average estimations derived from multiple methods showed that the regional background ρ（O3-8h） in Henan Province from 2019 to 2021 concentrations were 82.0, 79.0, and 79.7 µg·m-3, accounting for 75.9%, 76.4%, and 78.7% of the total regional O3-8h, respectively. The regional background O3-8h estimated by the four methods showed obvious seasonal changes, characterized by summer > spring > fall > winter.

The novel HLA-C*15:279 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

The novel HLA-C*15:279 allele differs from HLA-C*15:02:01:01 by five nucleotide substitutions in exons 4 and 5.

Oleanane-type triterpenoids from Sabia limoniacea and their anti-inflammatory activities.

Eighteen new oleanane-type triterpenoids were isolated from the stems of Sabia limoniacea, including sabialimon A (1), a triterpenoid with an unprecedented 6/6/6/7/7 pentacyclic skeleton and seventeen undescribed triterpenoids, sabialimons B-R (2 - 18), along with six previously described analogs (19 - 24). Their structures were fully elucidated via extensive spectroscopic analysis including 1D and 2D NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS), experimental electronic circular dichroism measurements and X-ray crystallographic studies. Compound 1 is the first triterpenoid that possesses a rare ring system (6/6/6/7/7) with an oxygen-bearing bridge between C-17 and C-18 and a hemiketal form at C-17, which is generated a larger ring by the degradation of C-28 and D/E-ring expansion. Biological evaluation revealed that sabialimon I (9), sabialimon K (11), sabialimon P (16) and 11,13(18)-oleanadien-28-hydroxymethyl 3-one (20) exhibited significantly inhibitory activities against nitric oxide (NO) release with IC50 values of 29.65, 23.41, 18.12 and 26.64 µM, respectively, as compared with the positive control (dexamethasone, IC50 value: 40.35 µM). Furthermore, sabialimon P markedly decreased the secretion of TNF-α, iNOS, IL-6 and NF-κB and inhibited the expression of COX-2 and NF-κB/p65 in LPS-induced RAW264.7 cells in a dose-dependent manner.

A multicenter, prospective, non-interventional real-world study to assess the effectiveness of mecapegfilgrastim in preventing neutropenia in patients with gastrointestinal cancer.

BACKGROUND: Mecapegfilgrastim, a long-acting granulocyte-colony stimulating factor has been approved for reducing the incidence of infection, particularly febrile neutropenia (FN), in China. OBJECTIVE: We conducted a multicenter prospective observational study to examine the safety and effectiveness of mecapegfilgrastim in preventing neutropenia in gastrointestinal patients receiving the chemotherapy, including S-1/capecitabine-based regimens or the fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI)/fluorouracil, leucovorin, and oxaliplatin (FOLFOX)/fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) regimens. METHOD: Five hundred and sixty-one gastrointestinal patients from 40 sites across China, between May 2019 and November 2021, were included. The administration of mecapegfilgrastim was prescribed at the discretion of local physicians. RESULTS: The most common adverse drug reactions (ADRs) of any grade for all patients was increased white blood cells (2.9%). Grade 3/4 ADRs were observed for anemia (0.2%), decreased white blood cells (0.2%), and decreased neutrophil count (0.2%). Among the 116 patients who received S-1/capecitabine-based chemotherapy throughout all cycles, ADRs of any grade included anemia (1.7%), myalgia (0.9%), and increased alanine aminotransferase (0.9%). No grade 3/4 ADRs were observed. In 414 cycles of patients who underwent S-1/capecitabine-based regimens, only one (0.2%) cycle experienced grade 4 neutropenia. In the FOLFIRINOX, FOLFOXIRI, and FOLFOX chemotherapy regimens, grade 4 neutropenia occurred in one (2.7%) of 37 cycles, four (4.7%) of 85 cycles, and two (1.2%) of 167 cycles, respectively. CONCLUSION: In a real-world setting, mecapegfilgrastim has proven effective in preventing severe neutropenia in gastrointestinal patients following chemotherapy. This includes commonly used moderate or high-risk FN regimens or regimens containing S1/capecitabine, all of which have demonstrated favorable efficacy and safety profiles.

CASQ2 alleviates lung cancer by inhibiting M2 tumor-associated macrophage polarization and JAK/STAT pathway.

Lung cancer (LC) is a major inducer of cancer-related death. We aim to reveal the effect of Calsequestrin2 (CASQ2) on macrophage polarization and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway in LC. Hub genes were determined from protein-protein interaction networks based on GSE21933 and GSE1987 data sets using bioinformatic analysis. Expression of hub genes was verified by real-time quantitative polymerase chain reaction (RT-qPCR). Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, wound-healing, colony formation, and transwell assays were performed to assess the impact of CASQ2 on LC cells. A xenograft mouse model was evaluated using hematoxylin-eosin, immunohistochemistry, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining to investigate the effect of CASQ2 on LC. The role of CASQ2 in regulating macrophage polarization and JAK/STAT pathway was evaluated by western blot andRT-qPCR. We screened out 155 common differentially expressed genes in GSE21933 and GSE1987 data sets. Myomesin-2, tyrosine kinase, sex determining region Y-box 2, platelet and endothelial cell adhesion molecule 1, matrix metallopeptidase 9, claudin-5, caveolin-1, CASQ2, recombinant ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 (ATP2A2), and ankyrin repeat domain 1 were identified as the hub genes with high prediction value. CASQ2 was selected as a pivotal regulator of LC. In vitro experiments and xenograft models revealed that CASQ2 overexpression suppressed proliferation, colony formation, migration, invasion of LC cells, and tumor growth in vivo. Additionally, overexpression of CASQ2 promoted the expression of M1 macrophage markers (cluster of differentiation 80 [CD80], interleukin [IL]-12, inducible nitric oxide synthase [iNOS]), while decreasing the expression of M2 macrophage markers (CD163, IL-10, Arg1) in tumor-associated macrophages and xenograft tissues. Finally, we found that overexpression of CASQ2 inhibited JAK/STAT pathway. CASQ2 is a novel biomarker, which can alleviate LC via inhibiting M2 tumor-associated macrophage polarization and JAK/STAT pathway.

SRP54 of black carp negatively regulates MDA5-mediated antiviral innate immunity.

Signal Recognition Particle 54 kDa (SRP54) is a subunit of the signal recognition particle (SRP), a cytoplasmic ribonucleoprotein complex guiding the transportation of newly synthesized proteins from polyribosomes to endoplasmic reticulum. In mammals, it has been reported to regulate the RLR signaling pathway negatively by impairing the association between MAVS and MDA5/RIG-I. However, the role of SRP54 in teleost antiviral innate immune response remains obscure. In this study, the SRP54 homolog of black carp (bcSRP54) has been cloned, and its function in antiviral innate immunity has been elucidated. The CDS of bcSRP54 gene consists of 1515 nucleotides and encodes 504 amino acids. Immunofluorescence (IF) showed that bcSRP54 was mainly distributed in the cytoplasm. Overexpressed bcSRP54 significantly reduced bcMDA5-mediated transcription of interferon (IFN) promoter in reporter assay. Co-expression of bcSRP54 and bcMDA5 significantly suppressed bcMDA5-mediated IFN signaling and antiviral activity, while bcSRP54 knockdown increased the antiviral ability of host cells. In addition, the results of the immunofluorescence staining demonstrated the subcellular overlapping between bcSRP54 and bcMDA5, and the co-immunoprecipitation (co-IP) experiment identified their association. Furthermore, the over-expression of bcSRP54 did not influence the protein expression and ubiquitination modification level of bcMDA5, however, hindered the binding of bcMDA5 to bcMAVS. In summary, our results conclude that bcSRP54 targets bcMDA5 and inhibits the interaction between bcMDA5 and MAVS, thereby negatively regulating antiviral innate immunity, which provides insight into how teleost SRP54 regulates IFN signaling.

The influence of open disc repositioning surgery on the internal derangement of the contralateral temporomandibular joint: a prospective study of 96 patients.

OBJECTIVE: To assess the influence of unilateral open disc repositioning surgery (ODRS) of the temporomandibular joint (TMJ) on the internal derangement (ID) of the contralateral joint. METHODS: Patients with bilateral ID of TMJ who underwent unilateral ODRS were enrolled and followed-up for one year. They were divided into two groups based on the contralateral disease: the anterior disc displacement with reduction (ADDWR) and without reduction (ADDWoR). Postoperative evaluation included clinical and MRI evaluation. Indices measured were unilateral intermaxillary distance (UID), visual analogue scale (VAS), disc length (DL), condylar height (CH), and disc-condyle angle (DCA). Paired t tests were used to compare the clinical and MRI indices between different time points. RESULTS: Ninety-six patients were enrolled, including 47 in the ADDWR group and 49 in the ADDWoR group. One-year post-surgery, ODRS led to significant increases in MMO, DL, and CH, and decrease in VAS and DCA on the operated side (P < 0.05). In ADDWR group, UID, DL, and CH increased significantly, and VAS decreased (P < 0.05), with no significant change in DCA (P > 0.05). In ADDWoR group, clinical and MRI variables worsened slightly, except for UID, which remained unchanged (P > 0.05). CONCLUSIONS: ODRS is a promising method for correcting TMJ ID and may improve condition of ADDWR and decrease progress of ADDWoR at the contralateral joint. Preoperative bilateral TMJ evaluation is essential for better outcomes. CLINICAL RELEVANCE: ODRS can effectively treat TMJ ID and produce adaptive changes in the contralateral ID, for which continuous monitoring of the contralateral joint is essential.

Swollen Necrotic Lymphadenitis Infected with Mycobacterium Paracondontium in an AIDS Patient: a Case Report and Literature Review.

Background: Non-tuberculous mycobacteria (NTM) are a group of mycobacteria that are commonly found in the environment and can cause disease in humans. The symptoms of NTM infection can be similar to those of tuberculosis, making diagnosis challenging. The morbidity associated with NTM is increasing, and clinical management can be challenging. Case Description: This report details the case of a 32-year-old male who was found to have multiple enlarged and partially necrotic lymph nodes in the neck, axilla, mediastinum, and retroperitoneum. The causative agent was rapidly identified as Mycobacterium paracondontium through pathogen-targeted sequencing (tNGS). After two weeks of treatment with azithromycin, moxifloxacin, rifabutin, and amikacin, the patient's uncomfortable symptoms had resolved, and he is currently undergoing further review. Conclusion: It is imperative that clinicians remain vigilant for the presence of NTM, particularly those that are rare, given their pervasiveness in the environment. Prompt diagnosis is of paramount importance, and molecular identification techniques represent a crucial tool in this regard. In vitro drug sensitivity testing should be conducted whenever feasible to guarantee the administration of an efficacious treatment regimen.

Sequential Reductive Dechlorination of Triclosan by Sediment Microbiota Harboring Organohalide-Respiring Dehalococcoidia.

Aquatic ecosystems represent a prominent reservoir of xenobiotic compounds, including triclosan (TCS), a broad-spectrum biocide extensively used in pharmaceuticals and personal care products. As a biogeochemical hotspot, the potential of aquatic sediments for the degradation of TCS remains largely unexplored. Here, we demonstrated anaerobic biotransformation of TCS in a batch microcosm established with freshwater sediment. The initial 43.4 ± 2.2 µM TCS was completely dechlorinated to diclosan, followed by subsequent conversion to 5-chloro-2-phenoxyphenol, a monochlorinated TCS (MCS) congener. Analyses of community profile and population dynamics revealed substrate-specific, temporal-growth of Dehalococcoides and Dehalogenimonas, which are organohalide-respiring bacteria (OHRB) affiliated with class Dehalococcoidia. Dehalococcoides growth was linked to the formation of diclosan but not MCS, yielding 3.6 ± 0.4 × 107 cells per µmol chloride released. A significant increase in Dehalogenimonas cells, from 1.5 ± 0.4 × 104 to 1.5 ± 0.3 × 106 mL-1, only occurred during the reductive dechlorination of diclosan to MCS. Dehalococcoidia OHRB gradually disappeared following consecutive transfers, likely due to the removal of sediment materials with strong adsorption capacity that could alleviate TCS's antimicrobial toxicity. Consequently, a solid-free, functionally stable TCS-dechlorinating consortium was not obtained. Our results provide insights into the microbial determinants controlling the environmental fate of TCS.

CO-driven electron and carbon flux fuels synergistic microbial reductive dechlorination.

BACKGROUND: Carbon monoxide (CO), hypothetically linked to prebiotic biosynthesis and possibly the origin of the life, emerges as a substantive growth substrate for numerous microorganisms. In anoxic environments, the coupling of CO oxidation with hydrogen (H2) production is an essential source of electrons, which can subsequently be utilized by hydrogenotrophic bacteria (e.g., organohalide-respring bacteria). While Dehalococcoides strains assume pivotal roles in the natural turnover of halogenated organics and the bioremediation of chlorinated ethenes, relying on external H2 as their electron donor and acetate as their carbon source, the synergistic dynamics within the anaerobic microbiome have received comparatively less scrutiny. This study delves into the intriguing prospect of CO serving as both the exclusive carbon source and electron donor, thereby supporting the reductive dechlorination of trichloroethene (TCE). RESULTS: The metabolic pathway involved anaerobic CO oxidation, specifically the Wood-Ljungdahl pathway, which produced H2 and acetate as primary metabolic products. In an intricate microbial interplay, these H2 and acetate were subsequently utilized by Dehalococcoides, facilitating the dechlorination of TCE. Notably, Acetobacterium emerged as one of the pivotal collaborators for Dehalococcoides, furnishing not only a crucial carbon source essential for its growth and proliferation but also providing a defense against CO inhibition. CONCLUSIONS: This research expands our understanding of CO's versatility as a microbial energy and carbon source and unveils the intricate syntrophic dynamics underlying reductive dechlorination.

Epithelium/imcDC2 axis facilitates the resistance of neoadjuvant anti-PD-1 in human NSCLC.

BACKGROUND: Therapeutic resistance is a main obstacle to achieve long-term benefits from immune checkpoint inhibitors. The underlying mechanism of neoadjuvant anti-PD-1 resistance remains unclear. METHODS: Multi-omics analysis, including mass cytometry, single-cell RNA-seq, bulk RNA-seq, and polychromatic flow cytometry, was conducted using the resected tumor samples in a cohort of non-small cell lung cancer (NSCLC) patients received neoadjuvant anti-PD-1 therapy. Tumor and paired lung samples acquired from treatment-naïve patients were used as a control. In vitro experiments were conducted using primary cells isolated from fresh tissues and lung cancer cell lines. A Lewis-bearing mouse model was used in the in vivo experiment. RESULTS: The quantity, differentiation status, and clonal expansion of tissue-resident memory CD8+ T cells (CD8+ TRMs) are positively correlated with therapeutic efficacy of neoadjuvant anti-PD-1 therapy in human NSCLC. In contrast, the quantity of immature CD1c+ classical type 2 dendritic cells (imcDC2) and galectin-9+ cancer cells is negatively correlated with therapeutic efficacy. An epithelium/imDC2 suppressive axis that restrains the antitumor response of CD8+ TRMs via galectin-9/TIM-3 was uncovered. The expression level of CD8+ TRMs and galectin-9+ cancer cell-related genes predict the clinical outcome of anti-PD-1 neoadjuvant therapy in human NSCLC patients. Finally, blockade of TIM-3 and PD-1 could improve the survival of tumor-bearing mouse by promoting the antigen presentation of imcDC2 and CD8+ TRMs-mediated tumor-killing. CONCLUSION: Galectin-9 expressing tumor cells sustained the primary resistance of neoadjuvant anti-PD-1 therapy in NSCLC through galectin-9/TIM-3-mediated suppression of imcDC2 and CD8+ TRMs. Supplement of anti-TIM-3 could break the epithelium/imcDC2/CD8+ TRMs suppressive loop to overcome anti-PD-1 resistance. TRIAL REGISTRATION NUMBER: NCT03732664.

Identification of QTL for Alkylresorcinols in Wheat and Development of KASP Markers for Marker-Assisted Selection of Health-Promoting Varieties.

This study evaluated alkylresorcinol concentration (ARC) in recombinant inbred lines (RILs) from the cross of Zhongmai 578 and Jimai 22 in three environments. ARC exhibited a continuous distribution ranging from 337.4 to 758.0, 495.4-768.0, and 456.3-764.7 µg/g, respectively, in three environments. Analysis of variance (ANOVA) indicated significant (P < 0.001) impacts of genotypes, environments, and their interactions. The broad-sense heritability of ARC was 0.76. Genome-wide linkage mapping analysis identified four stable quantitative trait loci (QTL) for ARC on chromosomes 2A, 3A, 4D, and 7A. Kompetitive allele-specific PCR (KASP) marker of each QTL was developed and validated in 206 representative wheat varieties. Wheat varieties harboring 0, 1, 2, 3, and 4 favorable alleles had ARC of 499.1, 587.8, 644.7, 668.5, and 711.1 µg/g, respectively. This study suggests that combining multiple minor-effect QTL through KASP markers can serve as an effective strategy for breeding high-ARC wheat, thereby enhancing innovations in functional food production.