A bifunctional amylopullulanase of Streptococcus suis ApuA contributes to immune evasion by interaction with host complement C3b.

The complement system is the first defense line of the immune system. However, pathogens have evolved numerous strategies to evade complement attacks. Streptococcus suis is an important zoonotic bacterium, harmful to both the pig industry and human health. ApuA has been reported as a bifunctional amylopullulanase and also contributed to virulence of S. suis. Herein, we found that ApuA could activate both classical and alternative pathways of the complement system. Furthermore, by using bacterial two-hybrid, far-western blot and ELISA assays, it was confirmed that ApuA could interact with complement C3b. The interaction domain of ApuA with C3b was found to be its α-Amylase domain (ApuA_N). After construction of an apuA mutant (ΔapuA) and its complementary strain, it was found that compared to the wild-type strain (WT), ΔapuA had significantly increased C3b deposition and membrane attack complex formation. Additionally, ΔapuA showed significantly lower survival rates in human serum and blood and was more susceptible to engulfment by neutrophils and macrophages. Mice infected with ΔapuA had significantly higher survival rates and lower bacterial loads in their blood, lung and brains, compared to those infected with WT. In summary, this study identified ApuA as a novel factor involved in the complement evasion of S. suis and suggested its multifunctional role in the pathogenesis of S. suis.

Prediction modeling of postoperative pulmonary complications following lung resection based on random forest algorithm.

Postoperative pulmonary complications (PPCs) are a significant concern following lung resection due to prolonged hospital stays and increased morbidity and mortality among patients. This study aims to develop and validate a risk prediction model for PPCs after lung resection using the random forest (RF) algorithm to enhance early detection and intervention. Data from 180 patients who underwent lung resections at the Third Affiliated Hospital of the Naval Medical University between September 2022 and February 2024 were retrospectively analyzed. The patients were randomly allocated into a training set and a test set in an 8:2 ratio. An RF model was constructed using Python, with feature importance ranked based on the mean Gini index. The predictive performance of the model was evaluated through analyses of the receiver operating characteristic curve, calibration curve, and decision curve. Among the 180 patients included, 47 (26.1%) developed PPCs. The top 5 predictive factors identified by the RF model were blood loss, maximal length of resection, number of lymph nodes removed, forced expiratory volume in the first second as a percentage of predicted value, and age. The receiver operating characteristic curve and calibration curve analyses demonstrated favorable discrimination and calibration capabilities of the model, while decision curve analysis indicated its clinical applicability. The RF algorithm is effective in predicting PPCs following lung resection and holds promise for clinical application.

Strategy and Methods for Carbon Emission Mitigation during Construction of Rail Transit.

The rail transit construction process produces a large quantity of carbon emission. The carbon emission could be divided into two sources, including direct carbon emission from the construction process and indirect carbon emission by raw material utilization. With the promotion of China National carbon peaking and carbon neutrality goals, it is an industry trend for the rail transit construction company to reduce carbon emission during the construction event. This study provides a detailed overview of the possible carbon emission process and carbon mitigation process during the rail transit construction event and puts forward preliminary carbon mitigation suggestions and strategy for the rail transit construction process. The predominant carbon emission section during rail transit construction is the raw material (including the steel, cement, concrete, tunnel segment), electricity, and fuel consumption during construction. It is suggested that the rail transit construction process could achieve carbon emission mitigation from the following prospects: make careful plans for the raw material selection (such as using recycled concrete, recycled steel, and so forth), improve the construction process to reduce energy waste, and optimize the equipment selection during the mechanical and electrical installment process. By this, the carbon emission could be mitigated during the rail transit construction.

Prediction of postoperative mortality in older surgical patients by clinical frailty scale: A systematic review and meta-analysis.

AIMS: To systematically evaluate the predictive efficacy of clinical frailty scale (CFS) for postoperative mortality older surgical patients, and to evaluate the prevalence of frailty in the included studies. DESIGN: A systematic review and meta-analysis of observational studies was conducted, utilizing the MOOSE guidelines for the evaluation of both. Quality assessment of the articles was also performed. DATA SOURCES: The protocol was registered (CRD42023423552). Relevant English and Chinese language studies published until October 20th, 2023 were retrieved from PubMed, Web of Science, Embase, Medline, CINAHL,Cochrane, WAN FANG DATA, VIP Information, CNKI, and SinoMed databases. REVIEW METHODS: Study were included in which frailty was measured by the CFS and postoperative mortality was reported for older surgery patients. A meta-analysis to predict postoperative mortality and frailty prevalence was performed using STATA 17.0 software. RESULTS: Sixteen cohort studies were included (5,864 participants) from 1,513 records. All studies' Newcastle-Ottawa Scale (NOS) scores were above 6 points. It was found that the prevalence of surgical frailty in the older was 0.36(CI 0.20-0.52). Patients assessed as frail by the CFS were associated with higher all-cause mortality (OR:4.01; CI 2.59-6.23). Subgroup analysis shows that frailty was associated with1-month mortality (OR:3.85; CI 1.11-13.45) and 1-year mortality (OR:4.43; CI 2.18-8.99). CONCLUSIONS: The prevalence of frailty is high in older surgical patients, and CFS can effectively predict the mortality of older surgical patients with frailty.

Metabolic interactions of host-gut microbiota: New possibilities for the precise diagnosis and therapeutic discovery of gastrointestinal cancer in the future-a review.

Gastrointestinal (GI) cancer continues to pose a significant global health challenge. Recent advances in our understanding of the complex relationship between the host and gut microbiota have shed light on the critical role of metabolic interactions in the pathogenesis and progression of GI cancer. In this study, we examined how microbiota interact with the host to influence signalling pathways that impact the formation of GI tumours. Additionally, we investigated the potential therapeutic approach of manipulating GI microbiota for use in clinical settings. Revealing the complex molecular exchanges between the host and gut microbiota facilitates a deeper understanding of the underlying mechanisms that drive cancer development. Metabolic interactions hold promise for the identification of microbial signatures or metabolic pathways associated with specific stages of cancer. Hence, this study provides potential strategies for the diagnosis, treatment and management of GI cancers to improve patient outcomes.

Dietary supplementation with a novel acidifier sodium diformate improves growth performance by increasing growth-related hormones levels and prevents Salmonella enterica serovar Pullorum infection in chickens.

Since the use of antibiotics as growth promoters in animal feed has been restricted or banned in several countries, finding suitable alternatives is crucial for maintaining animal health. In this study, a novel formate acidifier named sodium diformate (NaDF) was synthesized, and the effects on growth performance and the prevention effects against Salmonella enterica serovar Pullorum infections in chickens were assessed. In broilers, NaDF supplementation improved growth performance, as evidenced by increased body weights and reduced feed conversion ratios. At 38 days of age, NaDF supplementation increased the levels of growth-hormone and ghrelin in the serum, lowered pH values in the gut, improved duodenal morphology, as shown by increased villus length/crypt depth ratios. NaDF also modulated the abundance of beneficial and harmful bacteria without changing the general microbiota diversity and short-chain fatty acids levels, which would be beneficial for maintaining gut homeostasis during its use. NaDF exhibited a broad spectrum of antibacterial activity in vitro. Supplementation with NaDF effectively decreased S. Pullorum colonization in the cecum, liver and spleen in chickens, and mitigated pathological changes in the tissues. Therefore, as a novel acidifier, NaDF can improve chicken growth performance by increasing growth-related hormones levels while maintaining the diversity of gut microbiota, and also resist intestinal bacterial infection. These results provided evidences for the application of NaDF as an effective and safe animal feed in poultry farming.

Impact of low-to moderate-intensity exercise training on the mRNA expression of purine receptors across various vessels in SHR.

OBJECTIVE: In this study, we developed an exercise training protocol for assessing both blood pressure dynamics and mRNA expression levels of purine receptors in various vascular tissues during physical activity. The objective is to assess the impact of exercise training on blood pressure regulation in spontaneously hypertensive rats (SHR) and purine receptors in vascular tissues. METHODS: Wistar Kyoto (WKY) and SHR rats were randomly allocated into sedentary (Sed) and exercise training (ExT) groups. Rats in the Sed groups were allowed unrestricted movement, whereas those in the ExT groups underwent a 16-week regimen of low- to moderate-intensity treadmill exercise. Throughout the intervention period, blood pressure measurements and body weight recordings were conducted. Additionally, mRNA expressions of purine receptors P2X1, P2Y1, and P2Y2 in renal artery (RA), internal carotid artery (Int), thoracic aorta (Aor), and caudal artery (Cau) tissues were assessed. RESULTS: In the Sed group, body weight of SHR rats was observed to be lower compared to the three other groups. Over the course of the exercise regimen, blood pressure in the ExT group of SHR rats reduced gradually, converging towards levels similar to those observed in WKY rats by the conclusion of the exercise period. Regarding mRNA expression patterns of P2X1 receptors across the four blood vessels, WKY and SHR rats demonstrated similar sequences, consistently displaying the highest expression levels in the Cau. Conversely, mRNA expressions of P2Y1 and P2Y2 receptors exhibited distinct sequences across the four blood vessels in both WKY and SHR rats. Notably, compared to the Sed group of WKY rats, mRNA expression of P2X1 receptor in the Int of SHR rats revealed an increase, while expressions in the Aor of WKY rats and the Cau of SHR rats decreased following exercise. Expression of P2Y1 receptor mRNA decreased across all four types of blood vessels in SHR rats. Post-exercise, P2Y1 receptor mRNA expression increased in the Aor, decreased in the Cau of WKY rats, and increased in the Int and renal artery (RA) of SHR rats. Conversely, expressions of P2Y2 receptor mRNA decreased in the Int and Aor of SHR rats. Except for the Aor of WKY rats, expressions of P2Y2 receptor mRNA increased in the other arteries of both rat types following exercise. CONCLUSION: Differences in the distribution of purine receptor subtypes among distinct arterial segments in both WKY and SHR rats were observed. Exercise training was found to enhance mRNA expression levels of P2Y receptors in these rat models. This finding implies that exercise training might reduce hypertension in SHR rats by bolstering the purinergic relaxation response.

Recent racial/ethnic disparities in cancer-specific mortality among patients diagnosed with rectal cancer.

Background: African American patients frequently receive nonstandard treatment and demonstrate poorer overall survival (OS) outcomes compared to White patients. Our objective was to analysis whether racial/ethnic disparities in rectal cancer-specific mortality remain after accounting for clinical characteristics, treatment, and access-to-care-related factors. Methods: Individuals diagnosed with rectal cancer between 2011 and 2020 were identified using the Surveillance, Epidemiology, and End Results Database. The cumulative incidence of rectal cancer-specific mortality was computed. Sub-distribution hazard ratios (sdHRs) and 95% confidence intervals (CIs) for rectal cancer-specific mortality associated with race/ethnicity were estimated using Fine and Gray model with stepwise adjustments for clinical characteristics, treatment modalities, and factors related to access-to-care. Results: Among 54,370 patients, non-Hispanic (NH) Black individuals exhibited the highest cumulative incidence of rectal cancer-specific mortality (39%), followed by American Indian/Alaska Native (AI/AN) (35%), Hispanics (32%), NH-White (31%), and Asian/Pacific Islander (API) (30%). After adjusting for clinical characteristics, NH-Black patients had a 28% increased risk of rectal cancer mortality (sdHR, 1.28; 95% CI: 1.20-1.35) compared to NH-White patients. In contrast, mortality disparities between Hispanic-White, AI/AN-White, and API-White groups were not significant. The Black-White mortality differences persisted even after adjustments for treatment and access-to-care-related factors. In stratified analyses, among patients with a median household income below $59,999, AI/AN patients showed higher mortality than NH-Whites when adjusted for clinical characteristics (sdHR, 1.32; 95% CI: 1.03-1.70). Conclusions: Overall, the racial/ethnic disparities in rectal cancer-specific mortality were largely attributable to differences in clinical characteristics, treatment modalities, and factors related to access-to-care. These findings emphasize the critical need for equitable healthcare to effectively address and reduce the significant racial/ethnic disparities in rectal cancer outcomes.

Screening and assessment of malnutrition in patients with liver cirrhosis.

The development and advancement of malnutrition is associated not only with the progression of hepatic dysfunction, but also with cirrhosis-related complications. However, the prevalence of malnutrition reported in different studies varies widely due to differences in diagnostic methods and patient investigation settings. Therefore, we need to identify malnourished patients promptly and accurately. The purpose of this review was to compare the validity and reliability of nutritional screening tools and to select the most appropriate nutritional risk screening for patients with cirrhosis. We compared nutritional risk screening tools such as the Nutritional Risk Screening 2002 (NRS-2002), Malnutrition Universal Screening Tool (MUST), Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT) and Liver Disease Undernutrition Screening Tool (LDUST). Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT) is more feasible to screen cirrhotic patients for nutritional risk, and is highly reproducible, considering the impact of sodium and water retention; so it is practical to screen cirrhotic patients via RFH-NPT for nutritional risk, subsequently, to evaluate the nutritional status of patients with nutritional risk via the Global Leadership Initiative on Malnutrition (GLIM) diagnostic criteria. L3-SMI (third lumbar-skeletal muscle index) can accurately define sarcopenia in cirrhotic patients and also be used for clinical nutritional status assessment.

Supported IrO2 Nanocatalyst with Multilayered Structure for Proton Exchange Membrane Water Electrolysis.

The design of a low-iridium-loading anode catalyst layer with high activity and durability is a key challenge for a proton exchange membrane water electrolyzer (PEMWE). Here, the synthesis of a novel supported IrO2 nanocatalyst with a tri-layered structure, dubbed IrO2@TaOx@TaB that is composed of ultrasmall IrO2 nanoparticles anchored on amorphous TaOx overlayer of TaB nanorods is reported. The composite electrocatalyst shows great activity and stability toward the oxygen evolution reaction (OER) in acid, thanks to its dual-interface structural feature. The electronic interaction in IrO2/TaOx interface can regulate the coverage of surface hydroxyl groups, the Ir3+/ Ir4+ ratio, and the redox peak potential of IrO2 for enhancing OER activity, while the dense TaOx overlayer can prevent further oxidation of TaB substrate and stabilize the IrO2 catalytic layers for improving structural stability during OER. The IrO2@TaOx@TaB can be used to fabricate an anode catalyst layer of PEMWE with an iridium-loading as low as 0.26 mg cm-2. The low-iridium-loading PEMWE delivers high current densities at low cell voltages (e.g., 3.9 A cm-2@2.0 V), and gives excellent activity retention for more than 1500 h at 2.0 A cm-2 current density.

Analysis of assisted reproductive outcomes for gynecologic cancer survivors: a retrospective study.

OBJECTIVE: To examine the reproductive outcomes of assisted reproductive technology (ART) in gynecologic cancer patients and to assess maternal and neonatal complications. METHODS: Women diagnosed with gynecologic cancer who underwent their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment between 2013 and 2021 at Shanghai Ji Ai Genetics and IVF Institute were included in this study. Infertile women without any history of cancer were matched to the cancer group. The primary outcome was the cumulative live birth rate. Baseline and follow-up data were compared between groups using Student's t-tests for normally distributed variables and with Chi-square test for categorical variables. A propensity score-based patient-matching approach was adopted to ensure comparability between individuals with and without specific cancer type. RESULTS: A total of 136 patients with a history of gynecologic cancer and 241 healthy infertile controls were included in this study. Endometrial cancer constituted 50.70% of the cases and cervical cancer constituted 34.60% of the cases. The cancer group exhibited significantly shorter duration of stimulation, lower levels of estradiol, lower number of retrieved oocytes, day-3 embryos, and blastocysts compared to the control group (P < 0.05). The cumulative live birth rate of the gynecologic cancer group was significantly lower than that of the control group (36.10% vs. 60.50%, P < 0.001). Maternal and neonatal complications did not significantly differ between the groups (P > 0.05). The endometrial cancer and cervical cancer groups showed significantly lower cumulative live birth rates than their matched controls (38.60% vs. 64.50%, P = 0.011 and 24.20% vs. 68.60%, P < 0.001, respectively). CONCLUSIONS: These findings highlight the decreased occurrence of pregnancy and live birth in female gynecologic cancer patients undergoing ART, particularly in endometrial cancers and cervical cancers. These findings have important implications for counseling and managing gynecologic cancer patients undergoing ART.

[Comprehensive therapy of traditional Chinese medicine for erectile dysfunction with damp-heat stasis: A clinical observation of 103 cases].

OBJECTIVE: To assess the clinical effect and safety of comprehensive therapy of traditional Chinese medicine (TCM) in the treatment of erectile dysfunction (ED) with damp-heat stasis. METHODS: We selected 108 cases of ED with damp-heat stasis meeting the inclusion criteria and treated with tadalafil (the control group, n = 54) or tadalafil + comprehensive TCM therapy (the trial group, n = 54) in the First Affiliated Hospital of Henan University of Chinese Medicine in the same period. After 8 weeks of treatment, we recorded the patients' scores on IIEF-5, TCM syndrome, erectile quality (EQS), 9-Item Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Scale 7 (GAD-7). At 16 weeks of our study, we collected the efficacy parameters, safety indicators and adverse reactions by telephone follow-up and compared the data obtained between the two groups of patients. RESULTS: Totally, 103 of the patients completed the study, 51 in the control and 52 in the trial group. Compared with the baseline, the IIEF-5 and EQS scores were both markedly increased after 8 weeks of treatment in the trial group (12.35±3.00 vs 18.36±2.82, P< 0.05; 39.5 ï¼»30.25－43ï¼½ vs 67.5 ï¼»54.5－76.75ï¼½, P< 0.05) and the control (11.96±2.79 vs 15.88±3.86, P< 0.05; 38.0 ï¼»29－42ï¼½ vs 56 ï¼»49－64ï¼½, P< 0.05), even more significantly in the former than in the latter (P< 0.05); the TCM syndrome and GAD-7 scores were remarkably decreased in the trial (9.5 ï¼»8－12ï¼½ vs 4.0 ï¼»2.25－5ï¼½, P< 0.05; 5 ï¼»2.25－6.75ï¼½ vs 2.5 ï¼»1－4.75ï¼½, P< 0.05) and the control group (10.0 ï¼»8－12ï¼½ vs 5.0 ï¼»3－6ï¼½, P< 0.05; 5.0 ï¼»3－6ï¼½ vs 4.0 ï¼»2－5ï¼½, P< 0.05), even more significantly in the former than in the latter (P< 0.05), so were the PHQ-9 scores (P< 0.05), but with no statistically significant difference between the two groups (P > 0.05). The IIEF-5 scores of the two groups remained significantly higher than the baseline during the follow-up (P< 0.05), even higher in the trial than in the control group (17.04±2.60 vs 14.16±3.34, P< 0.05). No obvious abnormal safety indicators or adverse events were observed during the study. CONCLUSION: Comprehensive TCM therapy combined with tadalafil is superior to tadalafil alone in the treatment of ED with damp-heat stasis, and has a better long-term efficacy and a higher safety.

Hollow dodecahedral Zn0.3Cd0.7S@NiCo-mixed metal oxide p-n heterojunction with high-efficiency photocatalytic hydrogen production activity.

The growing demand for clean and sustainable energy has driven extensive research into efficient photocatalysts for hydrogen production. However, many semiconductor photocatalysts in this field still face the challenges such as wide band gap, limited visible light absorption, and inefficient separation and transport of photoinduced charges. In this study, nickel-cobalt layered double hydroxide (NiCo-LDH) was synthesized using an "etch-and-grow" method with zeolitic imidazolate framework-67 (ZIF-67) as a sacrificial template, followed by high-temperature calcination to produce nickel-cobalt mixed metal oxide (NiCo-MMO). Zn0.3Cd0.7S quantum dots were used to modify NiCo-MMO resulting in a hollow dodecahedral Zn0.3Cd0.7S@NiCo-MMO composite photocatalyst. In hydrogen production performance test, the optimized Zn0.3Cd0.7S@NiCo-MMO exhibited excellent performance (8177.5 µmol·g-1·h-1) and demonstrated good cycling stability. The hollow dodecahedral structure of the Zn0.3Cd0.7S@NiCo-MMO enhanced the light trapping ability and provided large surface area. The p-n heterojunction formed within Zn0.3Cd0.7S@NiCo-MMO accelerated carrier separation and transfer, effectively inhibited the recombination of photogenerated electrons and holes, and significantly improved the hydrogen production activity.

Biomarkers for congenital ventricular outflow tract malformations based on maternal serum lipid metabolomics analysis.

BACKGROUND: The congenital ventricular outflow tract malformations (CVOTMs) is a major congenital heart diseases (CHDs) subtype, and its pathogenesis is complex and unclear. Lipid metabolic plays a crucial role in embryonic cardiovascular development. However, due to the limited types of detectable metabolites in previous studies, findings on lipid metabolic and CHDs are still inconsistent, and the possible mechanism of CHDs remains unclear. METHODS: The nest case-control study obtained subjects from the multicenter China Teratology Birth Cohort (CTBC), and maternal serum from the pregnant women enrolled during the first trimester was utilized. The subjects were divided into a discovery set and a validation set. The metabolomics of CVOTMs and normal fetuses were analyzed by targeted lipid metabolomics. Differential comparison, random forest and lasso regression were used to screen metabolic biomarkers. RESULTS: The lipid metabolites were distributed differentially between the cases and controls. Setting the selection criteria of P value < 0.05, and fold change (FC) > 1.2 or < 0.833, we screened 70 differential metabolites. Within the prediction model by random forest and lasso regression, DG (14:0_18:0), DG (20:0_18:0), Cer (d18:2/20:0), Cer (d18:1/20:0) and LPC (0:0/18:1) showed good prediction effects in discovery and validation sets. Differential metabolites were mainly concentrated in glycerolipid and glycerophospholipids metabolism, insulin resistance and lipid & atherosclerosis pathways, which may be related to the occurrence and development of CVOTMs. CONCLUSION: Findings in this study provide a new metabolite data source for the research on CHDs. The differential metabolites and involved metabolic pathways may suggest new ideas for further mechanistic exploration of CHDs, and the selected biomarkers may provide some new clues for detection of COVTMs.

Device Stability and Photoelectric Conversion Evolution of PM6 Solar Cells Based on Different Acceptors.

To understand the effects of acceptors on morphology aging, photoelectric conversion evolution, and stability of PM6-based solar cells, multiple characterization techniques, including morphology, transient absorption, and electrical characterizations, were conducted to analyze the correlation among morphology aging, photoelectric conversion evolution, and performance degradation of devices. The results demonstrated that the morphology features of PM6:Y6 and PM6:PC71BM active layers would change with time due to their unstable bulk heterojunction structures. The unstable active layers determined the evolution of photoelectric conversion and the stability of the devices. Furthermore, morphology aging was responsible for the increase of charge recombination. Compared with PM6:PC71BM, more delocalized and localized polarons were generated in PM6:Y6 solar cells, and the increased probability of charge recombination with morphology aging was relatively smaller. Therefore, the PM6:Y6 device showed a higher efficiency and better stability than the PM6:PC71BM device.

Oxophilic gallium single atoms bridged ruthenium clusters for practical anion-exchange membrane electrolyzer.

The development of highly efficient and durable alkaline hydrogen evolution reaction (HER) catalysts is crucial for achieving high-performance practical anion exchange membrane water electrolyzer (AEMWE) at ampere-level current density. Herein, we report a design concept by employing Ga single atoms as an electronic bridge to stabilize the Ru clusters for boosting alkaline HER performance in practical AEMWE. Experimental and theoretical results collectively reveal that the bridged Ga sites trigger strong metal-support interaction for the homogeneous distribution of Ru clusters with high density, as well as optimize the Ru-H bond strength due to the electron transfer between Ru and Ga for enhanced intrinsic HER activity. Moreover, the oxophilic Ga sites near the Ru clusters tend to adsorb the hydroxyl species and accelerate the water dissociation for sufficient proton supplement in an alkaline medium. The Ru-GaSA/N-C catalyst exhibits a low overpotential of 4 ± 1 mV (10 mA cm-2) and high mass activity of 9.3 ± 0.5 A mg-1Ru at -0.05 V vs RHE. In particular, the Ru-GaSA/N-C-based AEMWE in 1 M KOH delivers a voltage of only 1.74 V to reach an industrial current density of 1 A cm-2, and can steadily operate at 1 A cm-2 for more than 170 h.

The role and mechanisms of cordycepin in inhibiting cancer cells.

With the escalating incidence and mortality rates of cancer, there is an ever-growing emphasis on the research of anticancer drugs. Cordycepin, the primary nucleoside antibiotic isolated from Cordyceps militaris, has emerged as a remarkable agent for cancer prevention and treatment. Functioning as a natural targeted antitumor drug, cordycepin assumes an increasingly pivotal role in cancer therapy. This review elucidates the mechanisms of cordycepin in inhibiting tumor cell proliferation, inducing apoptosis, as well as its capabilities in suppressing angiogenesis and metastasis. Moreover, the immunomodulatory effects of cordycepin in cancer treatment are explored. Additionally, the current status, challenges, and future prospects of cordycepin application in clinical trials are briefly discussed. The objective is to provide a valuable reference for the utilization of cordycepin in cancer treatment.

Therapeutic delivery of CCL2 modulates immune response and restores host-microbe homeostasis.

Many chronic inflammatory diseases are attributed to disturbances in host-microbe interactions, which drive immune-mediated tissue damage. Depending on the anatomic setting, a chronic inflammatory disease can exert unique local and systemic influences, which provide an exceptional opportunity for understanding disease mechanism and testing therapeutic interventions. The oral cavity is an easily accessible environment that allows for protective interventions aiming at modulating the immune response to control disease processes driven by a breakdown of host-microbe homeostasis. Periodontal disease (PD) is a prevalent condition in which quantitative and qualitative changes of the oral microbiota (dysbiosis) trigger nonresolving chronic inflammation, progressive bone loss, and ultimately tooth loss. Here, we demonstrate the therapeutic benefit of local sustained delivery of the myeloid-recruiting chemokine (C-C motif) ligand 2 (CCL2) in murine ligature-induced PD using clinically relevant models as a preventive, interventional, or reparative therapy. Local delivery of CCL2 into the periodontium inhibited bone loss and accelerated bone gain that could be ascribed to reduced osteoclasts numbers. CCL2 treatment up-regulated M2-macrophage and downregulated proinflammatory and pro-osteoclastic markers. Furthermore, single-cell ribonucleic acid (RNA) sequencing indicated that CCL2 therapy reversed disease-associated transcriptomic profiles of murine gingival macrophages via inhibiting the triggering receptor expressed on myeloid cells-1 (TREM-1) signaling in classically activated macrophages and inducing protein kinase A (PKA) signaling in infiltrating macrophages. Finally, 16S ribosomal ribonucleic acid (rRNA) sequencing showed mitigation of microbial dysbiosis in the periodontium that correlated with a reduction in microbial load in CCL2-treated mice. This study reveals a novel protective effect of CCL2 local delivery in PD as a model for chronic inflammatory diseases caused by a disturbance in host-microbe homeostasis.

Evaluating the role of high N2O affinity complete denitrifiers and non-denitrifying N2O reducing bacteria in reducing N2O emissions in river.

Freshwater rivers are hotspots of N2O greenhouse gas emissions. Dissolved organic carbon (DOC) is the dominant electron donor for microbial N2O reduction, which can reduce N2O emission through enriching high N2O affinity denitrifiers or enriching non-denitrifying N2O-reducing bacteria (N2ORB), but the primary regulatory pathway remains unclear. Here, field study indicated that high DOC concentration in rivers enhanced denitrification rate but reduced N2O flux by improving nosZ gene abundance. Then, four N2O-fed membrane aeration biofilm reactors inoculated with river sediments from river channel, estuary, adjacent lake, and a mixture were continuously performed for 360 days, including low, high, and mixed DOC stages. During enrichment stages, the (nirS+nirK)/nosZ ratio showed no significant difference, but the community structure of denitrifiers and N2ORB changed significantly (p < 0.05). In addition, N2ORB strains isolated from different enrichment stages positioned in different branches of the phylogenetic tree. N2ORB strains isolated during high DOC stage showed significant higher maximum N2O-reducing capability (Vmax: 0.6 ± 0.4 ×10-4 pmol h-1 cell-1) and N2O affinity (a0: 7.8 ± 7.7 ×10-12 L cell-1 h-1) than strains isolated during low (Vmax: 0.1 ± 0.1 ×10-4 pmol h-1 cell-1, a0: 0.7 ± 0.4 ×10-12 L cell-1 h-1) and mixed DOC stages (Vmax: 0.1 ± 0.1 ×10-4 pmol h-1 cell-1, a0: 0.9 ± 0.9 ×10-12 L cell-1 h-1) (p < 0.05). Hence, under high DOC concentration conditions, the primary factor in reducing N2O emissions in rivers is the enrichment of complete denitrifiers with high N2O affinity, rather than non-denitrifying N2ORB.