Designing Small Molecule PI3Kγ Inhibitors: A Review of Structure-Based Methods and Computational Approaches.

The PI3K/AKT/mTOR pathway plays critical roles in a wide array of biological processes. Phosphatidylinositol 3-kinase gamma (PI3Kγ), a class IB PI3K family member, represents a potential therapeutic opportunity for the treatment of cancer, inflammation, and autoimmunity. In this Perspective, we provide a comprehensive overview of the structure, biological function, and regulation of PI3Kγ. We also focus on the development of PI3Kγ inhibitors over the past decade and emphasize their binding modes, structure-activity relationships, and pharmacological activities. The application of computational technologies and artificial intelligence in the discovery of novel PI3Kγ inhibitors is also introduced. This review aims to provide a timely and updated overview on the strategies for targeting PI3Kγ.

Comparative study on the predictive value of TG/HDL-C, TyG and TyG-BMI indices for 5-year mortality in critically ill patients with chronic heart failure: a retrospective study.

BACKGROUND: The triglyceride glucose (TyG) index, TyG-body mass index (TyG-BMI), and triglyceride-density lipoprotein cholesterol ratio (TG/HDL-C) are substitute indicators for insulin resistance (IR). This study aimed to compare the predictive value of these indicators for 5-year mortality in critically ill patients with chronic heart failure (CHF). METHODS: Critically ill patients with CHF were identified from the Multiparameter Intelligent Monitoring in Intensive Care (MIMIC) III and IV databases. The primary outcome was 5-year mortality. The relationship between the three indices and mortality risk was determined using multivariate Cox proportional hazards models, Kaplan-Meier (K‒M) analysis and restricted cubic splines analysis. A receiver operating characteristic (ROC) curve was generated to compare the ability of the three indices to predict mortality. Finally, whether the IR indices would further increase the predictive ability of the basic model including baseline variables with a significance level between survivors and non-survivors was evaluated by ROC curve. RESULTS: Altogether, 1329 patients with CHF were identified from the databases. Cox proportional hazards models indicated that the TyG index was independently associated with an elevated risk of 5-year mortality (hazard ratio [HR], 1.56; 95% confidence interval [CI] 1.29-1.9), while the TyG-BMI index and TG/HDL-C level were significantly associated with 5-year mortality, with an HR (95% CI) of 1.002 (1.000-1.003) and 1.01 (1.00-1.03), respectively. The K-M analysis revealed that the cumulative incidence of all-cause 5-year death increased with increasing quartiles of the TyG index, TyG-BMI index, or TG/HDL-C ratio. According to the ROC curve, the TyG index outperformed the TyG-BMI and TG/HDL-C ratio at predicting all-cause 5-year mortality (0.608 [0.571-0.645] vs. 0.558 [0.522-0.594] vs. 0.561 [0.524-0.598]). The effect of the TyG index on all-cause mortality was consistent across subgroups, with no significant interaction with randomized factors. Furthermore, adding the TyG index to the basic model for 5-year mortality improved its predictive ability (area under the curve, 0.762 for the basic model vs. 0.769 for the basic model + TyG index); however, the difference was not statistically significant. CONCLUSION: As continuous variables, all three indices were significantly associated with 5-year mortality risk in critically ill patients with CHF. Although these IR indices did not improve the predictive power of the basic model in patients with CHF, the TyG index appears to be the most promising index (vs. TyG-BMI and TG/HDL-C ratio) for prevention and risk stratification in critically ill patients with CHF.

Social isolation and loneliness with risk of cardiometabolic multimorbidity: A prospective cohort study from UK Biobank.

The pandemic of the coronavirus disease 2019 resulted in an increased prevalence of social isolation and loneliness. Cox proportional hazards regression was used to test the association between social isolation/loneliness, multiple cardiometabolic diseases (CMDs) and cardiometabolic multimorbidity (CMM). In the multivariable adjusted models, compared with the least isolated, the most isolated had independently associated with CMD (HR 1.07, 95% CI 1.03 to 1.11) and CMM (HR 1.24, 95% CI 1.12 to 1.36) in stage I, and CMM in stage II (HR 1.14, 95% CI 1.05 to 1.23). Compared with those with the least loneliness, those who with most loneliness had about 20% increased risk of CMD and 29% increased risk of CMM in stage I. Those with the most loneliness were also significantly associated with increased CMM risk (HR 1.30, 95% CI 1.19 to 1.42) in stage II. This study revealed the associations of social isolation/loneliness with CMD and CMM.

Prevalence, Diversity, and Virulence of Campylobacter Carried by Migratory Birds at Four Major Habitats in China.

Campylobacter species, especially C. jejuni and C. coli, are the main zoonotic bacteria causing human gastroenteritis. A variety of Campylobacter species has been reported in wild birds, posing a potential avian-human transmission pathway. Currently, there has been little surveillance data on Campylobacter carriage in migratory birds in China. In the current work, fresh fecal droppings from individual migratory birds were collected at four bird wintering/stopover sites in China from May 2020 to March 2021. Nucleic acid was extracted and tested for Campylobacter with PCR-based methods. Overall, 73.8% (329/446) of the samples were positive for Campylobacter, demonstrating location and bird host specificity. Further speciation revealed the presence of C. jejuni, C. coli, C. lari, C. volucris, and an uncharacterized species, which all harbored a variety of virulence factors. Phylogenetic analysis performed on concatenated 16S rRNA-atpA-groEL genes elucidated their genetic relationship, demonstrating both inter- and intra-species diversity. The wide distribution and high diversity of Campylobacter spp. detected in migratory birds in China indicated potential transmission across territories. The existence of virulence factors in all of these species highlighted their public health importance and the necessity of monitoring and controlling Campylobacter and other pathogens carried by migratory birds.

Synchrony of Bird Migration with Global Dispersal of Avian Influenza Reveals Exposed Bird Orders.

Highly pathogenic avian influenza virus (HPAIV) A H5, particularly clade 2.3.4.4, has caused worldwide outbreaks in domestic poultry, occasional spillover to humans, and increasing deaths of diverse species of wild birds since 2014. Wild bird migration is currently acknowledged as an important ecological process contributing to the global dispersal of HPAIV H5. However, this mechanism has not been quantified using bird movement data from different species, and the timing and location of exposure of different species is unclear. We sought to explore these questions through phylodynamic analyses based on empirical data of bird movement tracking and virus genome sequences of clade 2.3.4.4 and 2.3.2.1. First, we demonstrate that seasonal bird migration can explain salient features of the global dispersal of clade 2.3.4.4. Second, we detect synchrony between the seasonality of bird annual cycle phases and virus lineage movements. We reveal the differing exposed bird orders at geographical origins and destinations of HPAIV H5 clade 2.3.4.4 lineage movements, including relatively under-discussed orders. Our study provides a phylodynamic framework that links the bird movement ecology and genomic epidemiology of avian influenza; it highlights the importance of integrating bird behavior and life history in avian influenza studies.

Genome-wide association study of cardiometabolic multimorbidity in the UK Biobank.

Considering the high prevalence and poor prognosis of cardiometabolic multimorbidity (CMM), identifying causal factors and actively implementing preventive measures is crucial. However, Mendelian randomization (MR), a key method for identifying the causal factors of CMM, requires knowledge of the effects of SNPs on CMM, which remain unknown. We first analyzed the genetic overlap of single cardiometabolic diseases (CMDs) using the latest genome-wide association study (GWAS) for evidential support and comparison. We observed strong positive genetic correlations and shared loci among all CMDs. Further, GWAS and post-GWAS analyses of CMM were performed in 407 949 European ancestry individuals from the UK Biobank. Eleven loci and 12 lead SNPs were identified. By comparison, we found these SNPs were a subset of SNPs associated with CMDs, including both shared and non-shared SNPs. Then, the polygenic risk score model predicted the risk of CMM (C-index = 0.62) and we identified candidate genes related to lipid metabolism and immune function. Finally, as an example, two-sample MR analysis based on the GWAS revealed potential causal effects of total cholesterol, serum urate, body mass index, and smoking on CMM. These results provide a basis for future MR research and inspire future studies on the mechanism and prevention of CMM.

S-nitrosylation of AMPKγ impairs coronary collateral circulation and disrupts VSMC reprogramming.

Collateral circulation is essential for blood resupply to the ischemic heart, which is dictated by the contractile phenotypic restoration of vascular smooth muscle cells (VSMC). Here we investigate whether S-nitrosylation of AMP-activated protein kinase (AMPK), a key regulator of the VSMC phenotype, impairs collateral circulation. In rats with collateral growth and development, nitroglycerin decreases coronary collateral blood flow (CCBF), inhibits vascular contractile phenotypic restoration, and increases myocardial infarct size, accompanied by reduced AMPK activity in the collateral zone. Nitric oxide (NO) S-nitrosylates human recombinant AMPKγ1 at cysteine 131 and decreases AMP sensitivity of AMPK. In VSMCs, exogenous expression of S-nitrosylation-resistant AMPKγ1 or deficient NO synthase (iNOS) prevents the disruption of VSMC reprogramming. Finally, hyperhomocysteinemia or hyperglycemia increases AMPKγ1 S-nitrosylation, prevents vascular contractile phenotypic restoration, reduces CCBF, and increases the infarct size of the heart in Apoe-/- mice, all of which is rescued in Apoe-/-/iNOSsm-/- mice or Apoe-/- mice with enforced expression of the AMPKγ1-C130A mutant following RI/MI. We conclude that nitrosative stress disrupts coronary collateral circulation during hyperhomocysteinemia or hyperglycemia through AMPK S-nitrosylation.

Malonic acid shapes bacterial community dynamics in compost to promote carbon sequestration and humic substance synthesis.

The incorporation of malonic acid (MA) into compost as a regulator of the tricarboxylic acid (TCA) cycle has the potential to increase carbon sequestration. However, the influence of MA on the transformation of the microbial community during the composting process remains unclear. In this investigation, MA was introduced at different stages of chicken manure (CM) composting to characterize the bacterial community within the compost using high-throughput sequencing. We assess the extent of increased carbon sequestration by comparing the concentration of total organic carbon (TOC). At the same time, this study examines whether increased carbon sequestration contributes to humus formation, which was elucidated by evaluating the content and composition of humus. Our results show that the addition of MA significantly improved carbon sequestration within the compost, reducing the carbon loss rate (C loss (%)) from 64.70% to 52.94%, while increasing HS content and stability. High throughput sequencing and Random Forest (RF) analysis show that the introduction of MA leads to a reduction in the diversity of the bacterial communities, but enhanced the ability of bacterial communities to synthesize humus. Furthermore, the addition of MA favors the proliferation of Firmicutes. Also, the hub of operational taxonomic units (OTUs) within the community co-occurrence network shifts from Proteobacteria to Firmicutes. Remarkably, our study finds a significant decrease in negative correlations between bacteria, potentially mitigating substrate consumption due to negative interactions such as competition. This phenomenon contributes to the improved retention of TOC in the compost. This research provides new insights into the mechanisms by which MA regulates bacterial communities in compost, and provides a valuable theoretical basis for the adoption of this innovative composting strategy.

Establishment of machine learning-based tool for early detection of pulmonary embolism.

BACKGROUND AND OBJECTIVES: Pulmonary embolism (PE) is a complex disease with high mortality and morbidity rate, leading to increasing society burden. However, current diagnosis is solely based on symptoms and laboratory data despite its complex pathology, which easily leads to misdiagnosis and missed diagnosis by inexperienced doctors. Especially, CT pulmonary angiography, the gold standard method, is not widely available. In this study, we aim to establish a rapid and accurate screening model for pulmonary embolism using machine learning technology. Importantly, data required for disease prediction are easily accessed, including routine laboratory data and medical record information of patients. METHODS: We extracted features from patients' routine laboratory results and medical records, including blood routine, biochemical group, blood coagulation routine and other test results, as well as symptoms and medical history information. Samples with a feature loss rate greater than 0.8 were deleted from the original database. Data from 4723 cases were retained, 231 of which were positive for pulmonary embolism. 50 features were retained through the positive and negative statistical hypothesis testing which was used to build the predictive model. In order to avoid identification as majority-class samples caused by the imbalance of sample proportion, we used the method of Synthetic Minority Oversampling Technique (SMOTE) to increase the amount of information on minority samples. Five typical machine learning algorithms were used to model the screening of pulmonary embolism, including Support Vector Machines, Logistic Regression, Random Forest, XGBoost, and Back Propagation Neural Networks. To evaluate model performance, sensitivity, specificity and AUC curve were analyzed as the main evaluation indicators. Furthermore, a baseline model was established using the characteristics of the pulmonary embolism guidelines as a comparison model. RESULTS: We found that XGBoost showed better performance compared to other models, with the highest sensitivity and specificity (0.99 and 0.99, respectively). Moreover, it showed significant improvement in performance compared to the baseline model (sensitivity and specificity were 0.76 and 0.76 respectively). More important, our model showed low missed diagnosis rate (0.46) and high AUC value (0.992). Finally, the calculation time of our model is only about 0.05 s to obtain the possibility of pulmonary embolism. CONCLUSIONS: In this study, five machine learning classification models were established to assess the likelihood of patients suffering from pulmonary embolism, and the XGBoost model most significantly improved the precision, sensitivity, and AUC for pulmonary embolism screening. Collectively, we have established an AI-based model to accurately predict pulmonary embolism at early stage.

Aging-Associated ALKBH5-m6A Modification Exacerbates Doxorubicin-Induced Cardiomyocyte Apoptosis Via AT-Rich Interaction Domain 2.

BACKGROUND: Chemotherapy-induced cardiovascular disease is a growing concern in the elderly population who have survived cancer, yet the underlying mechanism remains poorly understood. We investigated the role of ALKBH5 (AlkB homolog 5), a primary N6-methyladenosine (m6A) demethylase, and its involvement in m6A methylation-mediated regulation of targets in aging-associated doxorubicin-induced cardiotoxicity. METHODS AND RESULTS: To validate the relationship between doxorubicin-induced cardiotoxicity and aging, we established young and old male mouse models. ALKBH5 expression was modulated through adeno-associated virus 9 (in vivo), Lentivirus, and siRNAs (in vitro) to examine its impact on cardiomyocyte m6A modification, doxorubicin-induced cardiac dysfunction, and remodeling. We performed mRNA sequencing, methylated RNA immunoprecipitation sequencing, and molecular assays to unravel the mechanism of ALKBH5-m6A modification in doxorubicin-induced cardiotoxicity. Our data revealed an age-dependent increase in doxorubicin-induced cardiac dysfunction, remodeling, and injury. ALKBH5 expression was elevated in aging mouse hearts, leading to reduced global m6A modification levels. Through mRNA sequencing and methylated RNA immunoprecipitation sequencing analyses, we identified ARID2 (AT-rich interaction domain 2) as the downstream effector of ALKBH5-m6A modulation in cardiomyocytes. Further investigations revealed that ARID2 modulates DNA damage response and enhances doxorubicin-induced cardiomyocyte apoptosis. CONCLUSIONS: Our findings provide insights into the role of ALKBH5-m6A modification in modulating doxorubicin-induced cardiac dysfunction, remodeling, and cardiomyocyte apoptosis in male mice. These results highlight the potential of ALKBH5-targeted treatments for elderly patients with cancer in clinical settings.

Association between insulin resistance and uncontrolled hypertension and arterial stiffness among US adults: a population-based study.

BACKGROUND: Prior research has established the correlation between insulin resistance (IR) and hypertension. While the association between triglyceride-glucose (TyG) index, a reliable surrogate marker of IR, and uncontrolled hypertension as well as arterial stiffness among individuals with hypertension remains undisclosed. METHODS: In this study, a total of 8513 adults diagnosed with hypertension from the National Health and Nutrition Examination Survey 1999-2018 were included. The primary outcome of the study are arterial stiffness (represented with estimated pulse wave velocity, ePWV) and uncontrolled hypertension. Logistic regression model, subgroup analysis, restricted cubic spine, and smooth curve fitting curve were conducted to evaluate the association between the IR indicators and uncontrolled hypertension and arterial stiffness in individuals with hypertension. RESULTS: Among included participants, the overall prevalence of uncontrolled hypertension was 54.3%. After adjusting for all potential covariates, compared with the first quartile of TyG index, the risk of uncontrolled hypertension increased about 28% and 49% for participants in the third quartile (OR, 1.28; 95% CI 1.06-1.52) and the fourth quartile (OR, 1.49; 95% CI 1.21-1.89) of TyG index, respectively. The higher OR of TyG index was observed in participants taking antihypertensive medication [fourth quartile versus first quartile (OR, 2.03; 95% CI 1.37-3.11)]. Meanwhile, we explored the potential association between TyG index and arterial stiffness and found that TyG index was significantly associated with increased arterial stiffness (ß for ePWV, 0.04; 95% CI 0.00-0.08; P = 0.039). However, traditional IR indicator HOMA-IR showed no significant positive correlation to uncontrolled hypertension as well as arterial stiffness in US adults with hypertension. CONCLUSION: Elevated levels of the TyG index were positive associated with prevalence of uncontrolled hypertension and arterial stiffness among US adults with hypertension.

Improved carbon sequestration by utilization of ferrous ions during different organic wastes composting.

The humic acid (HA) possesses a more recalcitrant structure, making it crucial carbon components that improve carbon sequestration. Moreover, ferrous ions could improve microbial activity and enhance compost humification, and their oxidation into iron oxides could adsorb carbon components for sequestration. Based on the advantages of low cost and easy availability of ferrous sulfate (FeSO4), this study investigated the effect of FeSO4 on carbon sequestration during composting. Chicken manure (CM) and food waste (FW) composting were carried out in four treatments, namely control (CM, FW) and 5% (w/w) FeSO4 treated groups (CM+, FW+). Results indicated that FeSO4 increased HA content, improved organic carbon stability. Carbon loss for CM, CM+, FW and FW + treatments were 48.5%, 46.2%, 45.0%, and 40.3%, respectively. Meanwhile, FeSO4 enhanced the function of bacterial taxa involved in HA synthesis in CM + treatment, and improved the number of core bacteria significantly associated with formation of HA and iron oxide. SEM analysis verified that role of FeSO4 was significant in promoting HA synthesis during CM + composting, while it was remarkably in enhancing HA sequestration during FW + composting. This article provided fundamental theoretical backing for enhancing HA production and improving carbon sequestration during different materials composting.

1,5,6-Trimethoxy-2,7-dihydroxyphenanthrene from Dendrobium officinale Exhibited Antitumor Activities for HeLa Cells.

Natural products are irreplaceable reservoirs for cancer treatments. In this study, 12 phenanthrene compounds were extracted and isolated from Dendrobium officinale. Each chemical structure was identified using comprehensive NMR analysis. All compounds were evaluated for their cytotoxic activities against five tumor cell lines, i.e., HeLa, MCF-7, SK-N-AS, Capan-2 and Hep G2. Compound 5, 1,5,6-trimethoxy-2,7-dihydroxyphenanthrene, displayed the most significant cytotoxic effect against HeLa and Hep G2 cells, with an IC50 of 0.42 and 0.20 µM. For Hela cells, further experiments demonstrated that compound 5 could obviously inhibit cell migration, block cell cycle in the G0/G1 phase and induce apoptosis. Expression measurements for p53 indicated that knock down of p53 by siRNA could mitigate the apoptosis induced by compound 5. Therefore, the compound 5 is a potential candidate drug for HeLa cells in cervical cancer.

Origin, distribution and spatial characteristics of dissolved organic matter in the Heilongjiang River.

The Heilongjiang River Basin is a vast area with significant DOM sources and composition differences. The mechanism of DOM degradation under spatial variation remains unclear. This research investigated the degradation characteristics of DOM in different watersheds of the Heilongjiang River. DOM levels were higher in midstream waters, while DOM degradation rates were higher in midstream and downstream waters. The parallel factor analysis (PARAFAC) results showed that the upstream amino acid fraction was significantly depleted, the midstream was dominated by the degradation of DOM of terrestrial origin, and the downstream humic acid fraction was decreased considerably. Gene sequencing results indicated that the upstream, middle, and downstream water bodies' microbial community composition and structure differed significantly. The network analysis results revealed microorganisms in upstream water bodies mainly utilized amino acid-like substances and small molecule humic acids. Microorganisms in the middle and lower reaches of the water column were characterized by the utilization of humic acid-like fractions. In this study, we further screened the key driving microorganisms (e.g., Flavobacterium and Lacibacter) responsible for the difference in the DOM utilization function of upstream-to-midstream and midstream-to-downstream microorganisms in the Heilongjiang River. These findings will help identify the cycling process of DOM under spatial variation and predict the succession pattern of microbial communities.

Structure elucidation and NMR spectral assignments of one new dammarane-type triterpenoid saponin from black ginseng.

New dammarane-type triterpenoid saponin, named 22(R)-notoginsenoside Ab1 (1), together with thirteen known dammarane-type triterpenoid saponins (2-14) was isolated from the EtOH extract of black ginseng and their structures were elucidated on the basis of one- and two-dimensional NMR (including 1H-NMR, 13C-NMR, HSQC, HMBC, ROESY) and calculated ECD. Among them, compounds 1-2 and 6-8 were isolated for the first time from ginseng and black ginseng. Besides, the absolute structure of 22(R)- and 22(S)- notoginsenoside Ab1 were distinguished by ECD for the first time.

Effects of simulated precipitation gradients on nutrient resorption in the desert steppe of northern China.

Background: Changes in rainfall induced by climate change will likely influence the utilization of water resources and affect the nutrient cycle in plants in the water-limited desert steppe. In order to understand the response of nitrogen and phosphorus resorption characteristics of plant leaves to precipitation changes, this study compared the nitrogen (N) resorption efficiency, phosphorus (P) resorption efficiency and influencing factors of plants in a desert steppe through water treatment experiments. Methods: A 4-year field experiment was performed to examine the response and influencing factors of nitrogen (N) and phosphorus resorption efficiency of five dominant plants in Stipa breviflora desert steppe to simulated precipitation change in Inner Mongolia, with four simulated precipitation gradients including reducing water by 50%, natural precipitation, increasing water by 50%, increasing water by 100%. Results: Compared with natural precipitation, increasing water by 100% significantly increased soil moisture, and significantly increased the aboveground biomass of S. breviflora, C. songorica, A. frigida, decreased the N concentrations in green leaves of S. breviflora, Cleistogenes songorica, Artemisia frigida, Kochia prostrata, decreased the N concentrations in senesced leaves of C. songorica, decreased the P concentrations in green leaves of K. prostrata and Convolvulus ammannii, decreased the NRE of S. breviflora. NRE was significantly negatively correlated with N concentration in senesced leaves, and PRE was significantly negatively correlated with P concentration in senesced leaves. Conclusions: Increasing water indirectly reduces NRE by reducing plant leaf green leaves nitrogen concentration, and decreasing water indirectly reduces PRE by reducing soil moisture.

Efficacy and Safety of Single-Pill Combination of Rosuvastatin and Ezetimibe in Chinese Patients with Primary Hypercholesterolemia Inadequately Controlled by Statin Treatment (ROZEL): A Randomized, Double-Blind, Double Dummy, Active-Controlled Phase 3 Clinical Trial.

INTRODUCTION: Many patients with primary hypercholesterolemia do not achieve their plasma low-density lipoprotein cholesterol (LDL-C) goals with statin alone under a recommended dose of statin (e.g., 10 mg rosuvastatin) in China. The objective of this phase III study was to evaluate the efficacy and safety of a new single-pill combination (SPC) of rosuvastatin 10 mg/ezetimibe 10 mg (R10/E10) in this population. METHODS: This was a randomized, double-blind, double-dummy, active-controlled study in patients with primary hypercholesterolemia inadequately controlled with statin alone. The participants were randomized 1:1 to receive SPC R10/E10 or R10. The primary objective was to demonstrate the superiority of SPC R10/E10 vs. R10 in reducing the LDL-C levels after 8 weeks. RESULTS: This trial randomized 305 participants to SPC R10/E10 (n = 153) and R10 (n = 152). The superiority of SPC R10/E10 over R10 was demonstrated with the least square (LS) mean difference of percent change in LDL-C from baseline to week 8: - 13.85% (95% confidence interval [CI] - 20.15% to - 7.56%, P < 0.0001). The proportion of participants who achieved the LDL-C target (< 2.6 mmol/l) at week 8 was larger with SPC R10/E10 (n = 80, 54.1%) than with R10 (n = 42, 29.2%) (Odds ratio = 2.80, 95% CI 1.70 to 4.61, P < 0.0001). No unexpected safety findings were reported. CONCLUSION: The results suggest that SPC R10/E10 improve LDL-C reduction and goal achievement in Chinese patients with primary hypercholesterolemia not adequately controlled on statin therapy, without new safety findings. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04669041).

Exploring the nitrogen fixing strategy of bacterial communities in nitrogen cycling by adding calcium superphosphate at various periods during composting.

Chicken manure, as an organic solid waste with a high nitrogen content, generates large amounts of ammonia during composting, which leads to pollution of the surrounding environment, and causes a reduction in the quality of the compost product. Nitrogen is transformed through the nitrogen cycle and bacterial communities are the main contributors to the transformation of the nitrogen cycle. The microbial composition changes dramatically at different stages during composting. Therefore, calcium superphosphate (SSP) was added to compost as a nitrogen-fixing agent to elucidate the strategy and function of the bacterial community involved in the nitrogen cycle. The results showed that the addition of SSP at the initial, high temperature and cooling stages increased the inorganic nitrogen (NH4+-N, NO3--N) content by 51.99 %, 202.72 % and 173.37 % compared to CK, respectively. In addition, nitrogen cycle functional genes (gdh, nifH, pmoA-amoA, hao, nxrA, nirK, napA, nosZ, narG) abundance were determined by real-time qPCR. The nitrogen cycle genetic results showed that SSP addition at high temperature phase resulted in a 62.43 % down-regulation of ammonification genes, while nitrogen fixation and nitrification genes were enhanced. Random forests revealed a shift in the participation strategy of bacterial communities (e.g., Mycobacterium, Izemoplasmatales, Paracoccus, Ruminococcus) within the nitrogen cycle, leading to altered importance rankings despite involvement in different nitrogen cycle pathways. Moreover, Regression analysis and structural equation modelling revealed that SSP addition at high temperature stage stimulated the bacterial community engaged in nitrogen fixation and nitrification, resulting in increased nitrogen accumulation as NO3--N during composting. This paper offers the potential to yield novel scientific insights into the impact of microbially mediated nitrogen transformation processes and reduce gaseous pollution.

Lignans from the seed shells of Cerasus humilis (Bge.) Sok and their bioactivities.

The exploration of Cerasus humilis (Bge.) Sok seed shells yielded the identification of six previously uncharacterized compounds, in addition to twelve known compounds. Structure elucidation of these compounds relied on spectroscopic data analysis, and their absolute configurations were established by comparing calculated and experimental electronic circular dichroic (ECD) spectra, supplemented by interpretation of optical rotation data. Notably, none of these compounds exhibited cytotoxicity against HepG2 and A549 cell lines. Remarkably, a majority of the compounds displayed potent antioxidant activity.

The dominant role of cooperation in fungal community drives the humification process of chicken manure composting under addition of regulatory factors.

This study aimed to explore the action mechanism of fungal community on the enhancement of humification during chicken manure composting by regulating the core pathway of carbon metabolism - the tricarboxylic acid cycle. Regulators adenosine triphosphate (ATP) and malonic acid were added at the beginning of composting. The analysis of changes in humification parameters showed that the humification degree and stability of compost products were improved by adding regulators. Compared with CK, the humification parameters of adding regulators group increased by 10.98% on average. Meanwhile, adding regulators not only increased key nodes, but also strengthened the positive correlation between fungi, and network relationship was closer. Moreover, core fungi associated with humification parameters were identified by constructing OTU networks, and the division and cooperation mechanism of fungi were confirmed. Ultimately, the functional role of the fungal community acting on humification was confirmed by statistical means, that was, the fungal community promoting humification was the main group of composting process. And the contribution was more obvious in ATP treatment. This study was helpful to gain insight into the mechanism of regulators addition to advance the humification process, and provided new ideas for the safe, efficient and harmless disposal of organic solid waste.