Gut microbiome and metabolites mediate the benefits of caloric restriction in mice after acute kidney injury.

The role of gut microbiome in acute kidney injury (AKI) is increasing recognized. Caloric restriction (CR) has been shown to enhance the resistance to ischemia/reperfusion injury to the kidneys in rodents. Nonetheless, it is unknown whether intestinal microbiota mediated CR protection against ischemic/reperfusion-induced injury (IRI) in the kidneys. Herein, we showed that CR ameliorated IRI-elicited renal dysfunction, oxidative stress, apoptosis, and inflammation, along with enhanced intestinal barrier function. In addition, gut microbiota depletion blocked the favorable effects of CR in AKI mice. 16S rRNA and metabolomics analysis showed that CR enriched the gut commensal Parabacteroides goldsteinii (P. goldsteinii) and upregulated the level of serum metabolite dodecafluorpentan. Intestinal colonization of P. goldsteinii and oral administration of dodecafluorpentan showed the similar beneficial effects as CR in AKI mice. RNA sequencing and experimental data revealed that dodecafluorpentan protected against AKI-induced renal injury by antagonizing oxidative burst and NFκB-induced NLRP3 inflammasome activation. In addition, we screened and found that Hamaudol improved renal insufficiency by boosting the growth of P. goldsteinii. Our results shed light on the role of intestinal microbiota P. goldsteinii and serum metabolites dodecafluorpentan in CR benefits to AKI.

Dual trigger or hCG alone: A retrospective analysis on patients with diminished ovarian reserve under in vitro fertilization and embryo transfer (IVF-ET) treatment.

OBJECTIVE: With remarkable deficiency in both oocyte stock and competence, the prognosis of IVF-ET in diminished ovarian reserve (DOR) is obstinately poor, underscoring warranted optimization to current procedures. We compared the efficacy of dual-trigger (hCG plus GnRH-a) and hCG alone on the outcomes for DOR patients. STUDY DESIGN: A total of 381 couples and 857 controlled ovarian stimulation (COS) cycles, and 222 couples and 366 frozen embryo transfer (FET) ones were included. The intermediate outcomes during oocyte retrieval and in vitro culture were compared based on COS dataset, while outcomes after embryo transfer analyzed based on FET dataset. The marginal effect of all study factors and covariates were evaluated with a cluster-weighted GEE model. RESULTS AND CONCLUSION: Neither the intermediate nor implantation outcomes were improved by dual-trigger. The OR values were 1.08 (95 % CI: 0.41-2.78) for retrieval cancellation, 1.33 (95 % CI: 0.89-2.00) for oocyte harvest, 1.04(95 %CI: 0.94-1.15) for viable embryo and 1.03(95 %CI: 0.88-1.19) for top-quality embryo. Similarly, the ORs were 0.90 (95 %CI: 0.62-1.30) for implantation and 0.97 (95 %CI: 0.56-1.69) for clinical pregnancy. This equivalence remained unchanged after adjusting for the covariates such as age, BMI, controlled ovarian stimulation protocols, etc. Thus, dual-trigger cannot provide significant advantage over hCG in related to immediate or clinical outcomes of IVF-ET treatments in DOR patients.

[Chemical components and in vitro anti-aging activity of Yangxue Qingnao Wan based on UPLC-Q-TOF-MS/MS].

The main chemical components of Yangxue Qingnao Wan(YXQNW) were analyzed and identified by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS). According to the mass spectrometry information, Mass Hunter 10.0 analysis software was used to compare the collected quasi-molecular ion peaks and secondary fragment ions with literature and reference substances. A total of 131 compounds were identified from YXQNW, including 11 phenylpropanoids, 11 flavonoids, 42 nitrogen-containing compounds, 12 terpenoids, 17 phthalides, 23 quinones, and 15 other compounds. The anti-aging activity of YXQNW and six compounds from YXQNW, including rosmarinic acid, gallic acid, rutin, umbelliferone, hyperoside, and vanillic acid, were evaluated by D-galactose(D-gal)-induced HT22 cell senescence model. The effects of the compounds on HT22 cell damage and individual cell proliferation ability were observed from overall and individual perspectives by the Beyo Click~(TM) EdU-555 cell proliferation kit, and apoptosis was detected by the Annexin V-FITC/PI double staining apoptosis detection kit. Finally, the anti-aging effect of the compounds was tested by a cell senescence ß-galactosidase staining kit. This study provides a more comprehensive analysis of the chemical components of YXQNW and evaluates its anti-aging effect, which will provide a scientific basis for basic research on the efficacy of YXQNW for the treatment of various neurological diseases, such as Alzheimer's disease(AD), headache, and memory loss.

[Advances in bitterness receptors T2Rs in different diseases].

Bitterness, as one of the most important physiological sensations in animals, is primarily recognized through the mediation of bitter taste receptors. In recent years, it has been found that these receptors are not only expressed in taste bud cells on the tongue but also in the respiratory, cardiovascular, digestive, reproductive, and nervous systems. They are involved in regulating various fundamental physiological processes and are now considered important targets for the treatment of various diseases. This paper reviewed the structure, classification, distribution, and signaling pathways of bitter taste receptors, their relationship with different diseases, and the role of bitter taste receptors agonists, aiming to provide a basis for scientific research on bitter taste receptors.

Significant chlorine emissions from biomass burning affect the long-term atmospheric chemistry in Asia.

Biomass burning (BB) is a major source of trace gases and particles in the atmosphere, influencing air quality, radiative balance, and climate. Previous studies have mainly focused on the BB emissions of carbon and nitrogen species with less attention on chlorine. Reactive chlorine chemistry has significant effects on atmospheric chemistry and air quality. However, quantitative information on chlorine emissions from BB, particularly the long-term trend and associated atmospheric impacts, is limited both on regional and global scales. Here, we report a long-term (2001-2018) high-resolution BB emission inventory for the major chlorine-containing compounds (HCl, chloride, and CH3Cl) in Asia based on satellite observations. We estimate an average of 730 Gg yr-1 chlorine emitted from BB activity in Asia, with China contributing the largest share at 24.2% (177 Gg yr-1), followed by Myanmar at 18.7% and India at 18.3%. Distinct seasonal patterns and significant spatial and interannual variability are observed, mainly driven by human-mediated changes in agricultural activity. By incorporating the newly developed chlorine emission inventory into a global chemistry-climate model (CAM-Chem), we find that the BB-chlorine emissions lead to elevated levels of HCl and CH3Cl (monthly average up to 2062 and 1421 parts per trillion by volume (pptv), respectively), subsequently resulting in noticeable changes in oxidants (up to 3.1% in O3 and 17% in OH radicals). The results demonstrate that BB is not only a significant source of air pollutants but also of oxidants, suggesting a larger role of BB emissions in the atmospheric chemistry and oxidation process than previously appreciated. In light of the projected increase in BB activity toward the end of the century and the extensive control of anthropogenic emissions worldwide, the contribution of BB emissions may become fundamental to air quality composition in the future.

A low-swelling alginate hydrogel with antibacterial hemostatic and radical scavenging properties for open wound healing.

Development of a low-cost and biocompatible hydrogel dressing with antimicrobial, antioxidant, and low swelling properties is important for accelerating wound healing. Here, a multifunctional alginate hydrogel dressing was fabricated using the D-(+)-gluconic acidδ-lactone/CaCO3system. The addition of hyaluronic acid and tannic acid (TA) provides the alginate hydrogel with anti-reactive oxygen species (ROS), hemostatic, and pro-wound healing properties. Notably, soaking the alginate hydrogel in a poly-ϵ-lysine (EPL) aqueous solution enables the alginate hydrogel to be di-crosslinked with EPL through electrostatic interactions, forming a dense network resembling 'armor' on the surface. This simple one-step soaking strategy provides the alginate hydrogel with antibacterial and anti-swelling properties. Swelling tests demonstrated that the cross-sectional area of the fully swollen multifunctional alginate hydrogel was only 1.3 times its initial size, thus preventing excessive wound expansion caused by excessive swelling. After 5 h ofin vitrorelease, only 7% of TA was cumulatively released, indicating a distinctly slow-release behavior. Furthermore, as evidenced by the removal of 2,2-diphenyl-1-picrylhydrazyl free radicals, this integrated alginate hydrogel systems demonstrate a notable capacity to eliminate ROS. Full-thickness skin wound repair experiment and histological analysis of the healing site in mice demonstrate that the developed multifunctional alginate hydrogels have a prominent effect on extracellular matrix formation and promotion of wound closure. Overall, this study introduces a cost-effective and convenient multifunctional hydrogel dressing with high potential for clinical application in treating open wounds.

Personalized neoantigen cancer vaccines: current progression, challenges and a bright future.

Tumor neoantigens possess specific immunogenicity and personalized therapeutic vaccines based on neoantigens which have shown promising results in some clinical trials, with broad application prospects. However, the field is developing rapidly and there are currently few relevant review articles. Summarizing and analyzing the status of global personalized neoantigen vaccine clinical trials will provide important data for all stakeholders in drug development. Based on the Trialtrove database, a retrospective analysis was conducted using trial quantity as a key indicator for neo-adjuvant and adjuvant therapy anti-PD-1/PD-L1 clinical trials initiated before the end of 2022. The time trend of newly initiated trials was investigated. The sponsor type, host country, treatment mode, combination strategy, tested drugs, and targeted cancer types of these trials were summarized. As of December 2022, a total of 199 trials were included in the analysis. Among these studies, Phase I studies were the most numerous (119, 59.8%), and Phase I studies have been the predominant study type since 2015. Peptide vaccines were the largest neoantigen vaccines type, accounting for 64.8% of all clinical trials. Based on peptide delivery platforms, the proportion of trials was highest for the DC system (32, 16.1%), followed by LNP (11, 5.5%), LPX (11, 5.5%), and viruses (7, 3.5%). Most vaccines were applied in trials as a monotherapy (133/199, 66.8%), meanwhile combining immunotherapeutic drugs was the most common form for combination therapy. In terms of indications, the largest number of trials involved three or more unspecified solid tumors (50/199, 25.1%), followed by non-small cell lung cancer (24/199, 12.1%) and pancreatic cancer (15/199, 7.5%). The clinical development of personalized neoantigen cancer vaccines is still in the early stage. A clear shift in delivery systems from peptides to DC and liposomal platforms, with the largest number of studies in Asia, collectively marks a new era in the field. The adjuvant or maintenance therapy, and the combination treatment with ICIs are becoming the important clinical development orientation. As research on tumor-immune interactions intensifies, the design, development, and application of neoantigen vaccines are bound to develop rapidly, which will bring a new revolution in the future cancer treatment.

Comparative Analysis of the Feasibility of Myocardial Blood Flow Index Versus CT-FFR in the Diagnosis of Suspected Coronary Artery Disease.

Background: Using fluid dynamic modeling, noninvasive fractional flow reserve (FFR) derived from coronary computed tomography angiography (CCTA) data provides better anatomic and functional information than CCTA, with a high diagnostic and discriminatory value for diagnosing hemodynamically significant lesions. Myocardial blood flow index (MBFI) based on CCTA is a physiological parameter that reflects myocardial ischemia. Thus, exploring the relationship between computed tomography derived fractional flow reserve (CT-FFR) and MBFI could be clinically significant. This study aimed to investigate the relationship between CT-FFR and MBFI and to analyze the feasibility of MBFI differing from CT-FFR in diagnosing suspected coronary artery disease (CAD). Methods: Data from 61 patients (35 males, mean age: 59.2 ± 10.02 years) with suspected CAD were retrospectively analyzed, including the imaging data of CCTA, CT-FFR, and data of invasive coronary angiography performed within one week after hospitalization. CT-FFR and MBFI were calculated, and the correlation between MBFI or CT-FFR and invasive coronary angiography (ICA) was evaluated. Using ICA (value ≥ 0.70) as the gold standard and determining the optimal cutoff value via a diagnostic test, the diagnostic performance of MBFI or CT-FFR was evaluated. Results: MBFI and CT-FFR were negatively correlated with ICA (r = -0.3670 and -0.4922, p = 0.0036 and 0.0001, respectively). Using ICA (value of ≥ 0.70) the gold standard, the optimal cutoff value was 0.115 for MBFI, and the area under the curve (AUC) was 0.833 (95% confidence interval [CI]: 0.716-0.916, Z = 5.357, p < 0.0001); using ICA (value of ≥ 0.70) the gold standard, the optimal cutoff value was 0.80 for CT-FFR, and the area under the curve (AUC) was 0.759 (95% CI: 0.632-0.859, Z = 3.665, p = 0.0002). No significant difference was observed between the AUCs of CT-FFR and MBFI (Z = 0.786, p = 0.4316). Conclusions: MBFI based on CCTA can be used to evaluate myocardial ischemia similar to CT-FFR in suspected CAD; however, it should be noted that CT-FFR is a functional index based on the anatomical stenosis of the coronary artery, whereas MBFI is a physiological index reflecting myocardial mass remodeling.

Comprehensive landscapes of the causal network between immunity and sarcopenia.

Background: Inflammaging, an immune status characterized by a sustained increase in pro-inflammatory markers and a decline in anti-inflammatory mechanisms, is a critical risk factor in the development of sarcopenia. Landscapes of the causal relationships between immunity and sarcopenia are needed to understand the mechanism of sarcopenia and provide novel treatments comprehensively. Methods: We used Mendelian Randomization (MR) as the basic method in this study. By setting immune proteins, immune cells, and sarcopenia as exposures and outcomes alternatively, and then combining them in different directions, we potentially estimated their causal relationships and directions and subsequently mapped the comprehensive causal landscape based on this information efficiently. To further understand the network, we developed a method based on rank-sums to integrate multiple algorithms and identify the key immune cells and proteins. Results: More than 1,000 causal relationships were identified between immune cell phenotypes, proteins, and sarcopenia traits (p < 0.05), and the causal maps of these linkages were established. In the threshold of FDR < 0.05, hundreds of causal linkages were still significant. The final comprehensive map included 13 immune cell phenotypes and 8 immune proteins. The star factors in the final map included EM CD8br %CD8br, EM DN (CD4- CD8-) %DN, SIRT2, and so on. Conclusion: By reading the landscapes in this study, we may not only find the factors and the pathways that have been reported and proven but also identify multiple novel immunity cell phenotypes and proteins with enriched upstream and downstream pathways.

Solitary Myofibroma of the oral and maxillofacial regions in pediatric patients: A clinicopathological analysis of ten patients and review of 75 cases.

BACKGROUND: The imaging manifestations of oral and maxillofacial myofibroma/myofibromatosis can vary among patients. Although many clinical cases have been reported, a consensus on the clinicopathological features of and treatment principles for this disease is lacking. PURPOSE: This study aimed to summarize the clinicopathological features of solitary myofibroma of the oral and maxillofacial regions in pediatric patients. METHODS: The clinical data, histological features, and immunohistochemical characteristics of ten pediatric patients who underwent surgical removal and subsequent pathological diagnosis of myofibroma were collected and retrospectively and cross-sectionally analyzed. RESULTS: Seven patients were male, and 3 were female, with ages ranging from 3 months to 6 years (mean: 2.6 years). The patients presented with solitary lesions involving the mandibular gingiva and adjacent mandible (4 patients), mandible (2 patients), oral floor and submandibular area and adjacent mandible (1 patient), gingiva (1 patient), maxilla (1 patient), and oropharynx (1 patient). Light microscopy revealed spindle-shaped tumor cells organized in bundles or vortex patterns, forming a hemangiopericytoma-like perivascular pattern, whereas immunohistochemical staining revealed diffuse smooth muscle actin (SMA) positivity. All patients underwent surgical resection, and none experienced recurrence over the 12- to 82-month follow-up. CONCLUSIONS: Solitary myofibroma in the oral and maxillofacial regions is predominantly observed in infants and young children, with a higher incidence among males. The prognosis is favorable following localized lesion resection or curettage of jawbone lesions. Accurate recognition of the clinical, radiological, and pathological features of the disease will reduce the misdiagnosis rate.

Glutathione-Conjugated Fluorometric Ratiometric NIR-Silicon Nanoparticles and Its Applications for In Vitro and In Vivo Imaging.

Glutathione (GSH), a tripeptide molecule, is the most abundant nonprotein biothiol in living cells, playing a crucial role in preventing oxidative damage to cellular components and maintaining intracellular redox homeostasis. As a thiol molecule, GSH contains a sulfhydryl (-SH) group that is vital for the body's response to reactive oxygen species (ROS). To confirm whether GSH can be used as a bioindicator or in the early diagnosis of cancers at the cellular level, it is essential to achieve highly selective detection and conjugation of GSH to silicon nanoparticles (SiNPs) under pathological conditions. We are herein excited to report a type of fluorescent ratiometric near-infrared silicon nanoparticle (NIR-SiNP) probe, that is, glutathione peptide conjugated (NIR-SiNPs-GSH), which simultaneously possess small pore sizes at an average of 6.7 nm, an emission of 670 nm, a bioimaging functionality of living cancer cells and animals, and favorable biocompatibility. Taking advantage of these virtues, we further manifest that such resulting NIR-SiNPs, NIR-SiNPs-GSH bioprobes are marvelously worthy for immunofluorescence imaging of cancer cells and living mice. Furthermore, it was shown that DAPI and probes could selectively stain malignant tumor cell nuclei, indicating the possibility for bioimaging and identification of cancer cells and animals. In summary, the suggested NIR-SiNPs-GSH probe has the potential to be a very effective chemical tool for early tumor detection in the future.

Fabrication of hydrogen-bonded crosslinked hydrogel vitrimer with enhanced self-healing and printability via K+ induced low methyl apple pectin.

Low methyl pectin, conventionally extruded as sols and shaped through Ca2+ post-curing, face complexity and high production costs, limiting their application in 3D printing. We developed apple pectin (AP) vitrimer inks with shear-thinning behavior at elevated temperatures and self-supporting properties at low ones, via pectin methyl esterase (PME) modification and K+ induction, aiming to facilitate simpler extrusion 3D printing. PME-modified AP (PME-AP) exhibits a higher affinity for K+ compared to AP, attributed to an 8.76 % reduction in the degree of methyl esterification and a 9.72 % increase in the degree of blockiness. Consequently, 1 % PME-AP forms a robust hydrogel vitrimer characterized by a hardness of 121.33 g and a water holding capacity of 99.50 % at 150 mM K+, a 68 % reduction in K+ concentration requirement over AP gels. Through electrostatic shielding, K+ induces hydrogen-bonded crosslinked vitrimers with stress relaxation within 53 s at 80 °C and self-healing properties with minimal texture reduction (~2 g). These characteristics suggest that the hydrogen bond crosslinked vitrimer network can dynamically reorganize in response to temperature variations, making PME-AP gel ideal for 3D printing applications. This study establishes the groundwork for cost-efficient AP-based extrusion 3D printing.

Comparison of Different Intraoral Scanners With Prefabricated Aid on Accuracy and Framework Passive Fit of Digital Complete-Arch Implant Impression: An In Vitro Study.

OBJECTIVES: This study aimed to compare the accuracy of digital complete-arch implant impressions with prefabricated aids using three intraoral scanners (IOSs) and explore the correlation between virtual deviation measurement and physical framework misfit. MATERIALS AND METHODS: Four edentulous maxillary master models with four and six parallel and angular implants were fabricated and scanned by a laboratory scanner as reference scans. Ten scans of each master model were acquired using three IOSs (IOS-T, IOS-M, and IOS-A) with and without prefabricated aids. Trueness and precision of root mean square (RMS) errors were measured. Ten aluminum alloy frameworks were fabricated, and the misfit was measured with a micro-computed tomography scan with one screw tightened. RESULTS: Trueness and precision showed significant improvement when prefabricated aids were used for all three IOSs (p < 0.010). Median (interquartile range) RMS errors of trueness reduced from 67.5 (30.4) to 61.8 (30.3) µm, from 100.6 (35.4) to 45.9 (15.1) µm, and from 52.7 (33.2) to 41.1 (22.5) µm for scanner IOS-T, IOS-M, and IOS-A, respectively (p < 0.010). The precision of IOS-A and IOS-M was significantly better than IOS-T when using prefabricated aid (p < 0.001). RMS errors and the maximum marginal misfit of the framework were significantly correlated (p < 0.001, R2 = 0.845). CONCLUSIONS: With the prefabricated aids, the accuracy of IOSs enhanced significantly in digital complete-arch implant impressions. Three IOSs showed different levels of improvement in accuracy. Virtual RMS errors <62.2 µm could be the clinically acceptable threshold (150 µm) for framework passive fit.

A single-nucleus transcriptomic atlas characterizes cell types and their molecular features in the ovary of adult Nile tilapia.

In fish species, there is limited analysis of signature transcriptome profiles at the single-cell level in gonadal cells. Here, the molecular signatures of distinct ovarian cell categories in adult Nile tilapia (Oreochromis niloticus) were analysed using single-nucleus RNA sequencing (snRNA-seq). We identified four cell types (oogonia, oocytes, granulosa cell, and thecal cell) based on their specifically expressed genes and biological functions. Similarly, we found some key pathways involved in ovarian development that may affect germline-somatic interactions. A cell-to-cell communication network between the distinct cell types was constructed. We found that the bidirectional communication is mandatory for the development of germ cells and somatic cells in fish ovaries, and the granulosa cells and thecal cells play a central regulating role in the cell network in fish ovary. Additionally, we identified some novel candidate marker genes for various types of ovarian cells and also validated them using in situ hybridization. Our work reveals an ovarian atlas at the cellular and molecular levels and contributes to providing insights into oogenesis and gonad development in fish.

Taste Disturbance After Endoscopic Tympanoplasty with Tragal Cartilage Graft and Improvement Strategies.

Objectives: To explore the risk factors of early postoperative taste disturbance (EPTD) after type I endoscopic tympanoplasty and operative modification strategies to improve taste disturbance. Methods: This was a controlled study. One hundred and twenty-four patients who underwent type I endoscopic tympanoplasty with tragal cartilage graft were separated evenly into control and modified groups. The full-thickness tragus cartilage graft was placed close to the bony annulus to ensure drum integrity in the control group, and in the modified group, the cartilage graft was not in contact with the posterior-superior bony annulus, and the inferior-posterior of the scutum. Univariate and multivariate models were used to analyze the possible factors affecting EPTD and the prognosis of taste recovery. Results: The incidence of EPTD was significantly lower in the modification group (24.19%) than in the control group (56.45%) (OR: 4.24, 95% CI: 1.93-9.33, P < .001). Surgical manipulation of the chorda tympani nerve resulted in a higher incidence of EPTD (OR: 2.43; 95% CI: 1.06-5.57, P = .035). The size of the graft did not affect taste disturbance. No difference in the taste recovery rate was observed between the control and test groups (Z = -1.57, P = .116) after 3 months. The recovery rate of patients with manipulated chorda tympani nerves was still lower than that of patients without at 3 months (Z = -2.74, P = .006). Conclusion: Modified surgery and reduced manipulation of the chorda tympani nerve effectively reduce EPTD. Manipulated chorda tympani nerves may have a persistent effect on taste recovery.

Bacterial community composition of wheat aboveground compartments correlates with yield during the reproductive phase.

Plant-associated microbial communities play important roles in agricultural productivity, and their composition has been shown to vary across plant compartments and developmental stages. However, the response of microbial communities within different plant compartments and at different developmental stages to diverse long-term fertilization treatments, as well as their linkages with crop yields, remains underexplored. This study analyzed wheat-associated bacterial communities within various soil and plant compartments under three fertilization treatments throughout the vegetative and reproductive phases. The variance in bacterial community was primarily attributed to compartments, followed by fertilization treatments and developmental stages. The composition of belowground bacterial communities (bulk soil, rhizosphere soil, and root) exhibited stronger responses to fertilization treatments than aboveground compartments (stem and leaf). The composition of belowground bacterial communities responded to fertilization treatments at all developmental stages, and it was significantly correlated with crop yields during the vegetative phase, whereas the aboveground community composition only showed a response to fertilization during the reproductive phase, at which point it was significantly correlated with crop yields. Moreover, during this reproductive phase, the co-occurrence network of aboveground bacterial communities exhibited enhanced complexity, and it contained an increased number of keystone species associated with crop yields, such as Sphingomonas spp., Massilia spp., and Frigoribacterium spp. Structural equation modeling indicated that augmenting total phosphorus levels in aboveground compartments could enhance crop yields by increasing the relative abundance of these keystone species during the reproductive phase. These findings highlight the pivotal role of aboveground bacterial communities in wheat production during the reproductive phase. IMPORTANCE: The developmental stage significantly influences crop-associated bacterial communities, but the relative importance of bacterial communities in different compartments to crop yields across various stages is still not well understood. This study reveals that belowground bacterial communities during the vegetative phase are significantly correlated with crop yields. Notably, during the reproductive phase, the composition of aboveground bacterial communities was significantly correlated with crop yields. During this phase, the complexity and enriched keystone species within the aboveground co-occurrence network underscore their role in boosting crop production. These results provide a foundation for developing microbiome-based products that are phase-specific and promote sustainable agricultural practices.

The value of intervention with radiotherapy after first-line chemo-immunotherapy in locally advanced or metastatic esophageal squamous cell carcinoma: A multi-center retrospective study.

Background: Chemotherapy plus immunotherapy has become the standard first-line treatment of advanced or metastatic esophageal squamous cell carcinoma (ESCC), but median duration of response is only 7.0-8.3 months and progression-free survival (PFS, ∼6 months) is still far from satisfactory. We aim to evaluate whether early involvement of radiotherapy might improve the treatment outcome if objective response to first-line chemo-immunotherapy was observed in locally advanced or metastatic ESCC. Methods: Patients were retrospectively collected from 3 institutions in China. Patients with histopathologically confirmed diagnoses of locally advanced or metastatic ESCC were identified, who objectively responded to first-line chemo-immunotherapy (complete or partial response, or stable disease) and also received radiotherapy of primary lesions with radiation dose of over 40 Gy, with or without radiotherapy of metastatic lesions before the first disease progression. Results: A total of 72 eligible patients were identified. With median follow-up duration of 14.6 (range, 7.1-34.8) months, median progression-free survival (PFS) and overall survival (OS) were 13.5 (95 % CI,10.4-NA) months and 31.8 (95 % CI, 23.0-NA) months, respectively. Median duration from initiation of chemo-immunotherapy to radiotherapy was 2.9 (range, 0-15.1) months. Besides lower tumor burden as a significant factor of better treatment outcome, radiation dose ≥ 50 Gy was associated with superior PFS, while OS might be mainly related to tumor response to the induction chemo-immunotherapy. A low incidence of Grade 3 or above treatment-related adverse events were observed (19 %), and no treatment-related death occurred. Conclusion: Our multi-center retrospective study showed survival benefit brought by early involvement of radiotherapy after first-line chemo-immunotherapy for patients with locally advanced or metastatic ESCC. However, further investigation is warranted in future prospective, controlled trials to assess the value of radio-immunotherapy in advanced or metastatic ESCC.

A new isocoumarin derivative from endophytic fungus Pezicula neosporulosa VDB39 from Vaccinium dunalianum.

Four isocoumarin derivatives (1-4) and five phenols (5-9) were obtained from the endophytic fungus Pezicula neosporulosa VDB39, which was isolated from the branches of Vaccinium dunalianum Wight (Ericaceae). Compound 1 is a new derivative of isocoumarin. The structures were elucidated by spectroscopic methods. Single X-ray crystallography confirmed the absolute configuration of compound 1. Additionally, the antiphytopathogenic fungi activity of isocoumarin derivatives (1-4) was evaluated.

[Identification of chemical components of large-leaf yellow tea by ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry].

Large-leaf yellow tea, a slightly fermented yellow tea that is unique to China, has a stronger hypoglycemic effect than other tea varieties, such as green and black tea. Research on large-leaf yellow tea has focused on its hypoglycemic effect owing to the lack of comprehensive techniques to characterize its chemical components; thus, its development and further promotion are limited. Therefore, the development of a reliable analytical method to fully characterize the chemical components of large-leaf yellow tea is urgently required. In this study, a reliable strategy based on the data-acquisition technology of ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q TOF/MS) was established to rapidly screen and analyze the main chemical components of large-leaf yellow tea by combining the information of neutral loss groups and characteristic fragment ions. The chromatographic separation experiments were performed on a Waters ACQUITY UPLC BEH C18 column (100 mm×2.1 mm, 1.7 µm) with gradient elution using 0.1% formic acid aqueous solution and acetonitrile as the mobile phases. The flow rate was 0.2 mL/min, the sample volume was 2 µL, and the column temperature was 35 ℃. The mass spectral information of the components in a large-leaf yellow tea solution was collected using the full-information tandem MS (MSE) technique in positive and negative ion modes. The specific chemical components of large-leaf yellow tea was identified as follows. First, a self-established database of tea chemical components was constructed based on the literature. The mass spectral cleavage pathways of different types of compounds in large-leaf yellow tea were then sorted using reference substances, and the characteristics of the fragment ions and neutral loss groups were summarized. The precise mass-to-charge ratio of the target chemical components were then obtained based on the mass spectral information. Finally, the structures of the compounds in large-leaf yellow tea were confirmed based on their chromatographic retention times, mass spectral cleavage pathways, characteristic fragment ions, and neutral loss groups. A total of 87 chemical components, including 10 catechins, 32 flavonoids, 16 phenolic acids, 12 tannins, 6 theaflavins, and 11 compounds in other classes, were identified in large-leaf yellow tea. Representative compounds of various classes, including gallocatechin gallate, quercetin, vitexin, gallic acid, chlorogenic acid, 1,3,6-tri-O-galloyl-ß-D-glucose, and theaflavin, were selected, and their characteristic fragment ions and neutral loss groups were investigated in detail to reveal the cleavage pathways of different types of compounds in large-leaf yellow tea. The UPLC-Q TOF/MS method established in this study can comprehensively identify the main chemical components of large-leaf yellow tea in a simple, highly sensitive, stable, and reliable manner. This study provides a scientific basis and data support for the discovery of functional ingredients and quality evaluation of large-leaf yellow tea.