SpotGF: Denoising spatially resolved transcriptomics data using an optimal transport-based gene filtering algorithm.

Spatially resolved transcriptomics (SRT) combines gene expression profiles with the physical locations of cells in their native states but suffers from unpredictable spatial noise due to cell damage during cryosectioning and exposure to reagents for staining and mRNA release. To address this noise, we developed SpotGF, an algorithm for denoising SRT data using optimal transport-based gene filtering. SpotGF quantifies diffusion patterns numerically, distinguishing widespread expression genes from aggregated expression genes and filtering out the former as noise. Unlike conventional denoising methods, SpotGF preserves raw sequencing data, thereby avoiding false positives that can arise from imputation. Additionally, SpotGF demonstrates superior performance in cell clustering, identifying potential marker genes, and annotating cell types. Overall, SpotGF has the potential to become a crucial preprocessing step in the downstream analysis of SRT data. The SpotGF software is freely available at GitHub. A record of this paper's transparent peer review process is included in the supplemental information.

The effectiveness of psychological interventions on diabetes distress and glycemic level in adults with type 2 diabetes: a systematic review and meta-analysis.

AIMS: The treatment of diabetes distress plays an important role in diabetes care; however, no meta-analysis has been performed to synthesize the short- and long-term effects of psychological interventions tailored for diabetes distress in people with type 2 diabetes. We aim to evaluate the evidence on tailored psychological interventions for diabetes distress as the primary outcome, focusing on individuals with type 2 diabetes. METHODS: Two reviewers independently searched eight databases from their inception to September 2024. EndNote X9 was used to screen records. The Revised Cochrane risk-of-bias tool for randomized trials was used to assess the risk of bias. The GRADE system was used to assess the overall certainty of the evidence. A random effect model was used to determine the mean difference or standardized mean difference with 95% CIs. Subgroup analyses based on several intervention characteristics and sensitivity analyses were also conducted. RESULTS: Totally, 22,279 records were yielded, and we finally included 18 studies in our systematic review. The meta-analysis included data from 16 studies representing 1639 participants. Interventions types included mindfulness-based and cognitive behavioral therapy, among others. Duration of interventions ranged from 4 weeks to 6 months. We found that psychological interventions that measured diabetes distress significantly reduced diabetes distress in the short-term in people with type 2 diabetes (SMD= -0.56; 95% CI= -0.90, -0.22; p = 0.001). Subgroup analysis indicated that this effect could be enhanced when delivered in a group format, by psychologist, using a technology component, or including participants having elevated baseline diabetes distress. However, the short- and long-term effects on HbA1c were non-significant, with results showing (MD = 0.02; 95% CI = -0.23 to 0.26; p = 0.89) and (MD = -0.27; 95% CI = -0.64 to 0.10; p = 0.15), respectively. The long-term effect on diabetes distress was also non-significant (SMD = -0.45; 95% CI = -0.93 to 0.03; p = 0.07). CONCLUSIONS: Psychological interventions tailored for diabetes distress in people with type 2 diabetes are effective in reducing the level of diabetes distress immediately after the intervention. More trials are still needed to further enrich the evidence in this area.

Targeting osteoblastic 11ß-HSD1 to combat high-fat diet-induced bone loss and obesity.

Excessive glucocorticoid (GC) action is linked to various metabolic disorders. Recent findings suggest that disrupting skeletal GC signaling prevents bone loss and alleviates metabolic disorders in high-fat diet (HFD)-fed obese mice, underpinning the neglected contribution of skeletal GC action to obesity and related bone loss. Here, we show that the elevated expression of 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1), the enzyme driving local GC activation, and GC signaling in osteoblasts, are associated with bone loss and obesity in HFD-fed male mice. Osteoblast-specific 11ß-HSD1 knockout male mice exhibit resistance to HFD-induced bone loss and metabolic disorders. Mechanistically, elevated 11ß-HSD1 restrains glucose uptake and osteogenic activity in osteoblast. Pharmacologically inhibiting osteoblastic 11ß-HSD1 by using bone-targeted 11ß-HSD1 inhibitor markedly promotes bone formation, ameliorates glucose handling and mitigated obesity in HFD-fed male mice. Taken together, our study demonstrates that osteoblastic 11ß-HSD1 directly contributes to HFD-induced bone loss, glucose handling impairment and obesity.

The applied study to improve the treatment of knee sports injuries in ultimate frisbee players based on personalized exercise prescription: a randomized controlled trial.

Objective: Ultimate frisbee can lead to severe sports injuries, especially joint injuries in the lower limbs, such as knee meniscus injuries. This study examines the impact of personalized exercise therapy on knee meniscus injuries in ultimate frisbee players in the Lingnan region of China. Methods: Seventy-six patients with confirmed meniscal injuries participated in the study, divided into an intervention group (n = 38) and a control group (n = 38). The control group received standard treatment, including drug therapy and physical therapy. The intervention group received standard treatment plus a personalized exercise regimen based on FITT-VP (frequency, intensity, time, type, volume, and progression) principles, incorporating strength training, aerobic exercise, flexibility training, neuromuscular training, and aquatic exercise. This program was monitored and adjusted over a six-month period through both online and offline methods. The primary outcomes were joint range of motion (ROM), thigh circumference atrophy index (TCAI), Lysholm Rating Scale (LRS) scores, and visual analog scores (VAS). The secondary outcome was the International Knee Documentation Committee (IKDC) score. Data were collected before the intervention, and at 1 month and 6 months after the intervention. Statistical analysis was conducted using SPSS 24.0 and GraphPad 10.0, with a significance level set at α = 0.05. Results: After 1 month, the intervention group showed significantly better results in ROM (116.67 ± 9.063), LRS score (86.316 ± 3.750), and IKDC score (80.473 ± 5.421) compared to the control group (111.784 ± 4.778, 82.579 ± 3.818, and 77.684 ± 4.430, respectively) (p < 0.05). The TCAI (3.219 ± 1.889) and VAS score (1.921 ± 0.673) in the intervention group were significantly lower than those in the control group (5.228 ± 2.131 and 2.710 ± 1.112, respectively) (p < 0.01). After 6 months, the differences in LRS and VAS scores between the groups were not significant. However, the intervention group continued to show significant improvements in ROM (134.934 ± 3.011), TCAI (1.107 ± 1.158), and IKDC score (93.315 ± 1.847) compared to the control group (125.395 ± 18.554, 4.574 ± 1.109, and 87.789 ± 4.437, respectively) (p < 0.05). Conclusion: Personalized exercise prescriptions offer significant therapeutic and rehabilitative benefits for ultimate frisbee players with knee meniscus injuries. This approach helps to reduce symptoms, alleviate pain, and improve joint function, muscle strength, and athletic performance after sports-related injuries.

Targeting Parkin-regulated metabolomic change in cartilage in the treatment of osteoarthritis.

Articular cartilage degeneration may lead to osteoarthritis (OA) during the aging process, but its underlying mechanism remains unknown. Here, we found that chondrocytes exhibited an energy metabolism shift from glycolysis to oxidative phosphorylation (OXPHOS) during aging. Parkin regulates various cellular metabolic processes. Reprogrammed cartilage metabolism by Parkin ablation decreased OXPHOS and increased glycolysis, with ameliorated aging-related OA. Metabolomics analysis indicated that lauroyl-L-carnitine (LLC) was decreased in aged cartilage, but increased in Parkin-deficient cartilage. In vitro, LLC improved the cartilage matrix synthesis of aged chondrocytes. In vivo, intra-articular injection of LLC in mice with anterior cruciate ligament transaction (ACLT) ameliorated OA progression. These results suggest that metabolic changes are regulated by Parkin-impaired cartilage during aging, and targeting this metabolomic changes by supplementation with LLC is a promising treatment strategy for ameliorating OA.

LncRNA sequencing reveals an essential role for the lncRNA-mediated ceRNA network in penile squamous cell carcinoma.

Penile squamous cell carcinoma (PSCC) is becoming increasingly common and posing a severe threat to men's health, particularly in developing countries. The function of long non-coding RNAs (lncRNAs) in PSCC progression remains mysterious. Therefore, we explored the significance of lncRNAs in the competing endogenous RNA (ceRNA) network in PSCC tumor progression. The 5 healthy and 6 tumor tissue samples were subjected to lncRNA sequencing. Using miRcode, LncBase, miRTarBase, miRWalk, and TargetScan, we constructed a ceRNA network of differentially expressed lncRNAs, miRNAs, and mRNAs. Our analysis resulted in a ceRNA network consisting of 4 lncRNAs, 18 miRNAs, and 38 mRNAs, whose upstream regulators, the lncRNAs MIR205HG, MIAT, HCP5, and PVT1, were all elevated in PSCC. Immunohistochemical staining confirmed that cell proliferation-related genes TFAP2C, MKI67, and TP63, positively regulated by 4 lncRNAs, were considerably overexpressed in tumor tissues. Immune analysis revealed a significant upregulation in macrophage and exhausted T cell infiltration in PSCC. Our study identified a lncRNA-miRNA-mRNA ceRNA network for PSCC, revealing possible molecular mechanisms involved in the regulation of PSCC progression by key lncRNAs and their connections to the immunosuppressive tumor microenvironment. The ceRNA network provides a novel perspective for elucidating the pathogenesis of PSCC.

An expanded odorant-binding protein mediates host cue detection in the parasitic wasp Baryscapus dioryctriae basis of the chromosome-level genome assembly analysis.

BACKGROUND: Baryscapus dioryctriae (Chalcidodea: Eulophidae) is a parasitic wasp that parasitizes the pupae of many Pyralidae members and has been used as a biological control agent against Dioryctria pests of pinecones. RESULTS: This B. dioryctriae assembly has a genome size of 485.5 Mb with a contig N50 of 2.17 Mb, and scaffolds were assembled onto six chromosomes using Hi-C analysis, significantly increasing the scaffold N50 to 91.17 Mb, with more than 96.13% of the assembled bases located on chromosomes, and an analysis revealed that 94.73% of the BUSCO gene set. A total of 54.82% (279.27 Mb) of the assembly was composed of repetitive sequences and 24,778 protein-coding genes were identified. Comparative genomic analysis demonstrated that the chemosensory perception, genetic material synthesis, and immune response pathways were primarily enriched in the expanded genes. Moreover, the functional characteristics of an odorant-binding protein (BdioOBP45) with ovipositor-biased expression identified from the expanded olfactory gene families were investigated by the fluorescence competitive binding and RNAi assays, revealing that BdioOBP45 primarily binds to the D. abietella-induced volatile compounds, suggesting that this expanded OBP is likely involved in locating female wasp hosts and highlighting a direction for future research. CONCLUSIONS: Taken together, this work not only provides new genomic sequences for the Hymenoptera systematics, but also the high-quality chromosome-level genome of B. dioryctriae offers a valuable foundation for studying the molecular, evolutionary, and parasitic processes of parasitic wasps.

Design of a Helicobacter pylori multi-epitope vaccine based on immunoinformatics.

Helicobacter pylori (H. pylori) is an infectious bacterium that colonizes the stomach of approximately half of the global population. It has been classified as a Group I carcinogen by the World Health Organization due to its strong association with an increased incidence of gastric cancer and exacerbation of stomach diseases. The primary treatment for H. pylori infection currently involves triple or quadruple therapy, primarily consisting of antibiotics and proton pump inhibitors. However, the increasing prevalence of antibiotic resistance poses significant challenges to this approach, underscoring the urgent need for an effective vaccine. In this study, a novel multi-epitope H. pylori vaccine was designed using immunoinformatics. The vaccine contains epitopes derived from nine essential proteins. Software tools and online servers were utilized to predict, evaluate, and analyze the physiochemical properties, secondary and tertiary structures, and immunogenicity of the candidate vaccine. These comprehensive assessments ultimately led to the formulation of an optimal design scheme for the vaccine. Through constructing a novel multi-epitope vaccine based on immunoinformatics, this study offers promising prospects and great potential for the prevention of H. pylori infection. This study also provides a reference strategy to develop multi-epitope vaccines for other pathogens.

Methanogenic Potential of Sewer Microbiomes and Its Implications for Methane Emission.

The sewer system, despite being a significant source of methane emissions, has often been overlooked in current greenhouse gas inventories due to the limited availability of quantitative data. Direct monitoring in sewers can be expensive or biased due to access limitations and internal heterogeneity of sewer networks. Fortunately, since methane is almost exclusively biogenic in sewers, we demonstrate in this study that the methanogenic potential can be estimated using known sewer microbiome data. By combining data mining techniques and bioinformatics databases, we developed the first data-driven method to analyze methanogenic potentials using a data set containing 633 observations of 53 variables obtained from literature mining. The methanogenic potential in the sewer sediment was around 250-870% higher than that in the wet biofilm on the pipe and sewage water. Additionally, k-means clustering and principal component analysis linked higher methane emission rates (9.72 ± 51.3 kgCO2 eq m-3 d-1) with smaller pipe size, higher water level, and higher potentials of sulfate reduction in the wetted pipe biofilm. These findings exhibit the possibility of connecting microbiome data with biogenic greenhouse gases, further offering insights into new approaches for understanding greenhouse gas emissions from understudied sources.

Bifunctional In-MOFs for Selective and Sensitive Detection of Trace Nitrobenzene Compounds in Water and Possessing High Proton Conductivity.

With the escalating prevalence of terrorism and global environmental pollution, nitroaromatic compounds (NACs) have increasingly come into focus as the primary culprit. To counter these challenges, it is imperative to develop simple and efficient methods for detecting NACs. Considering the electron-deficient structure of NAC molecules, this paper constructed a novel three-dimensional In-MOF with permanent porosity using electron-rich organic molecules 4'-[1,2,2-tris(3',5'-dicarboxy[1,1'-biphenyl]-4-yl)ethenyl]-[1,1'-biphenyl]-3,5-dicarboxylic acid (H8ETTB) for fluorescence detection by photoinduced electron transfer. The results indicated that In-ETTB can sensitively detect trace NACs in water. In-ETTB exhibited the best detection performance for 3-NP, achieving a Ksv value of 8.75 × 104 M-1 with a limit of detection of 0.27 µΜ in aqueous solution; this belongs to a relatively high level among the reported metal organic framework (MOF) materials. Subsequently, anti-interference experiments revealed that In-ETTB exhibits strong specificity fluorescence recognition of NACs, and it could still maintain its structural integrity and fluorescence emission intensity even after 7 cycles of testing. We confirmed that the fluorescence detection of NACs was due to a combined effect of competitive absorption and photoinduced electron transfer through experimental collaboration DFT calculations in detail. Meanwhile, the proton conductivity reached 2.45 × 10-2 S·cm-1 at 98% relative humidity and 90 °C, which is also a high level in MOFs. This work provides a universal method theoretical basis for designing NAC detectors with practical application prospects.

Molecular characteristics of sea spray aerosols during aging with the participation of marine volatile organic compounds.

Sea spray aerosols (SSAs) are one of the largest natural sources of aerosols globally, known to affect the earth's radiation budget and to play a pivotal role in air quality and climate. The physical and chemical properties of organic components in SSA change during long-distance atmospheric transport over the ocean. To characterize the evolution of organic components during the aging process of SSA, in this study, we use a flow reactor to simulate the oxidation processes of SSA produced by authentic seawater via OH radicals (in the presence of organic gases evaporated from seawater) and to present the molecular signatures of the nascent and aged SSA. We found, under our experimental conditions, that oxidation of headspace organic gases during aging leads to significant formation of new particles and changes in the chemical constituents of SSA. In the nascent and aged SSA samples, we retained 129 and 340 products, respectively. The formation of high O/C and low carbon-number products was observed during the aging process, corresponding to functionalization and fragmentation reactions. Moreover, the significant contributions of compounds containing multiple nitrogen atoms and sulfate groups were observed in aged SSA for the first time, which can be attributed to the accretion reaction driven by OH heterogeneous oxidation and the formation of organic sulfur compounds, respectively. These findings provide additional insights into the atmospheric transformation of organic components in marine aerosols, which is important for understanding the global carbon cycle.

Hyperuricemia and its related diseases: mechanisms and advances in therapy.

Hyperuricemia, characterized by elevated levels of serum uric acid (SUA), is linked to a spectrum of commodities such as gout, cardiovascular diseases, renal disorders, metabolic syndrome, and diabetes, etc. Significantly impairing the quality of life for those affected, the prevalence of hyperuricemia is an upward trend globally, especially in most developed countries. UA possesses a multifaceted role, such as antioxidant, pro-oxidative, pro-inflammatory, nitric oxide modulating, anti-aging, and immune effects, which are significant in both physiological and pathological contexts. The equilibrium of circulating urate levels hinges on the interplay between production and excretion, a delicate balance orchestrated by urate transporter functions across various epithelial tissues and cell types. While existing research has identified hyperuricemia involvement in numerous biological processes and signaling pathways, the precise mechanisms connecting elevated UA levels to disease etiology remain to be fully elucidated. In addition, the influence of genetic susceptibilities and environmental determinants on hyperuricemia calls for a detailed and nuanced examination. This review compiles data from global epidemiological studies and clinical practices, exploring the physiological processes and the genetic foundations of urate transporters in depth. Furthermore, we uncover the complex mechanisms by which the UA induced inflammation influences metabolic processes in individuals with hyperuricemia and the association with its relative disease, offering a foundation for innovative therapeutic approaches and advanced pharmacological strategies.

Acroamine A, a 2-Amino Adenine Alkaloid from the Marine Soft Coral Acrozoanthus australiae and Its Semisynthetic Derivatives That Inhibit cAMP-Dependent Protein Kinase A Catalytic Subunit Alpha.

A high throughput screen performed to identify catalytic inhibitors of the oncogenic fusion form of cAMP-dependent protein kinase A catalytic subunit alpha (J-PKAcα) found an individual fraction from an organic extract of the marine soft coral Acrozoanthus australiae as active. Bioassay-guided isolation led to the identification of a 2-amino adenine alkaloid acroamine A (1), the first secondary metabolite discovered from this genus and previously reported as a synthetic product. As a naturally occurring protein kinase inhibitor, to unambiguously assign its chemical structure using modern spectroscopic and spectrometric techniques, five N-methylated derivatives acroamines A1-A5 (2-6) were semisynthesized. Three additional brominated congeners A6-A8 (7-9) were also semisynthesized to investigate the structure-activity relationship of the nine compounds as J-PKAcα inhibitors. Compounds 1-9 were tested for J-PKAcα and wild-type PKA inhibitory activities, which were observed exclusively in acroamine A (1) and its brominated analogs (7-9) achieving moderate potency (IC50 2-50 µM) while none of the N-methylated analogs exhibited kinase inhibition.

From pathogenesis to antigens: the key to shaping the future of TB vaccines.

Tuberculosis (TB) remains one of the gravest global health challenges. Mycobacterium tuberculosis (M. tuberculosis), the causative agent, employs sophisticated immune evasion and pathogenesis strategies. Its capability to thrive within immune cells and incite robust inflammatory responses prolongs infection and dissemination. Mycobacterial advanced adaptations facilitate navigation through the human immune system and present a variable antigenic profile throughout different infection stages. Investigating these strategies unfolds targeted approaches to effective vaccine development against TB. This review delves into the most advanced and exhaustive insights into the immune evasion tactics and pathogenic processes of M. tuberculosis across various infection stages. The knowledge distilled from this analysis holds the promise of guiding the creation of innovative TB vaccines and translating theoretical groundwork into practical immunological defenses.

AQP4-AS1 Can Regulate the Expression of Ferroptosis-Related Regulator ALOX15 through Competitive Binding with miR-4476 in Lung Adenocarcinoma.

Background The AQP4-AS1/miR-4476-ALOX15 regulatory axis was discovered in previous studies. We aimed to investigate the regulatory mechanism of the ferroptosis-related regulator ALOX15 by AQP4-AS1 and miR-4476 in lung adenocarcinoma (LUAD) and find new targets for clinical treatment. Methods After bioinformatics analysis, we contained one ferroptosis-related gene (FRG), namely ALOX15. MicroRNAs (miRNAs) and long noncoding RNAs were predicted by miRWalk. Furthermore, we constructed overexpressed LUAD cell lines. Real-time quantitative polymerase chain reaction and western blot were used to determine the expression of mRNA and protein, respectively. Cell Counting Kit-8 (CCK-8) and EdU assay were used to detect the cell proliferation. Double luciferase assay was used to detect the binding relationship between AQP4-AS1 and miR-4464. Results ALOX15 was the most significantly downregulated FRG compared with normal tissues. Furthermore, protein-protein interaction network analysis indicated that the AQP4-AS1-miR-4476-ALOX15 regulatory axis might be involved in the occurrence and development of LUAD and there might be direct interaction between AQP4-AS1 and miR-4476, and miR-4476 and ALOX15. Furthermore, AQP4-AS1 and ALOX15 were significantly downregulated in the LUAD tissue and cell lines, whereas miR-4476 showed the opposite results ( p < 0.001). AQP4-AS1 overexpression improved the ALOX15 expression in LUAD cell lines. CCK-8 and EdU assay revealed that overexpression of AQP4-AS1 and ALOX15 inhibited the LUAD cell proliferation. Double luciferase assay results indicated that there was a combination between AQP4-AS1 and miRNA-4476. In addition, we found that overexpressed AQP4-AS1 activates the ferroptosis in LUAD cell lines. Conclusions AQP4-AS1 can regulate the expression of ALOX15 through competitive binding with miR-4476, further activate ferroptosis and inhibit the proliferation of LUAD cells.

Trans-rectovesical pouch urethral-sparing robotic-assisted simple prostatectomy: A case series.

Objective: To detail a novel technique of robotic-assisted simple prostatectomy that makes handling the gland protruding into the bladder neck easier and can preserve the urethra and retain ejaculation function as much as possible. Patients and methods: This is a prospective case series. Clinical data of 17 male patients who had large volume (>80 mL) benign prostatic hyperplasia (BPH) were enrolled to undergo trans-rectovesical pouch urethral-sparing robotic-assisted simple prostatectomy (usRASP). We adopted the approach through the space between the bladder neck and seminal vesicle to perform a usRASP that can avoid the detrusor skirt and fibrous matrix area of the retropubic prostate. Between the transitional zone and the peripheral zone of the large prostate, the hyperplastic prostatic gland tissue can be enucleated under direct vision while preserving the prostatic urethra and retaining the ejaculatory duct and bladder neck intact. All preoperative, perioperative and postoperative clinical data were collected, and descriptive analysis was performed. Results: The median intravesical prostatic protrusion was 19.3 mm (8.5-32.2). The median operative time was 100 min (75-140), and the median estimated blood loss was 100 mL (10-500). The median time to catheter removal was 7 days (5-7), with a median postoperative hospital stay of 2 days (2-4). After at least 6-month follow-up, the median maximum urine flow rate and postvoid residual volume were 40.1 mL/s (12.7-52.4) and 15 mL (5-23), respectively; the median International Prostate Symptom Score and Quality of Life score were 0 (0-6.3) and 1 (0-3), respectively; and the median total prostate-specific antigen was 0.84 ng/mL (0.15-1.01). All patients successfully underwent usRASP. Fifty-eight percent of patients with normal ejaculation function before surgery can still retain normal ejaculation function. Conclusion: We described a new approach to performing usRASP. This new method remarkably improved the voiding function, maintained antegrade ejaculation and did not increase the post-operative complications.

Candidate Antigens and the Development of Helicobacter pylori Vaccines.

BACKGROUND: Infection with Helicobacter pylori (Hp) mostly occurs during childhood, and persistent infection may lead to severe gastric diseases and even gastric cancer. Currently, the primary method for eradicating Hp is through antibiotic treatment. However, the increasing multidrug resistance in Hp strains has diminished the effectiveness of antibiotic treatments. Vaccination could potentially serve as an effective intervention to resolve this issue. AIMS: Through extensive research and analysis of the vital protein characteristics involved in Hp infection, we aim to provide references for subsequent vaccine antigen selection. Additionally, we summarize the current research and development of Hp vaccines in order to provide assistance for future research. MATERIALS AND METHODS: Utilizing the databases PubMed and the Web of Science, a comprehensive search was conducted to compile articles pertaining to Hp antigens and vaccines. The salient aspects of these articles were then summarized to provide a detailed overview of the current research landscape in this field. RESULTS: Several potential antigens have been identified and introduced through a thorough understanding of the infection process and pathogenic mechanisms of Hp. The conserved and widely distributed candidate antigens in Hp, such as UreB, HpaA, GGT, and NAP, are discussed. Proteins such as CagA and VacA, which have significant virulence effects but relatively poor conservatism, require further evaluation. Emerging antigens like HtrA and dupA have significant research value. In addition, vaccines based on these candidate antigens have been compiled and summarized. CONCLUSIONS: Vaccines are a promising method for preventing and treating Hp. While some Hp vaccines have achieved promising results, mature products are not yet available on the market. Great efforts have been directed toward developing various types of vaccines, underscoring the need for developers to select appropriate antigens and vaccine formulations to improve success rates.

Design, synthesis, and biological evaluation of (thio)urea derivatives as potent Escherichia coli ß-glucuronidase inhibitors.

EcGUS has drawn considerable attention for its role as a target in alleviating serious GIAEs. In this study, a series of 72 (thio)urea derivatives were designed, synthesised, and biologically assayed. The bioassay results revealed that E-9 (IC50 = 2.68 µM) exhibited a promising inhibitory effect on EcGUS, surpassing EcGUS inhibitor D-saccharic acid-1,4-lactone (DSL, IC50 = 45.8 µM). Additionally, the inhibitory kinetic study indicated that E-9 (Ki = 1.64 µM) acted as an uncompetitive inhibitor against EcGUS. The structure-activity relationship revealed that introducing an electron-withdrawing group into the benzene ring at the para-position is beneficial for enhancing inhibitory activity against EcGUS. Furthermore, molecular docking analysis indicated that E-9 has a strong affinity to EcGUS by forming interactions with residues Asp 163, Tyr 472, and Glu 504. Overall, these results suggested that E-9 could be a potent EcGUS inhibitor, providing valuable insights and guidelines for the development of future inhibitors targeting EcGUS.

Modified SMILE (mSMILE) is active in the treatment of pediatric Epstein-Barr virus-associated natural killer/T-cell lymphoma: a single center experience, case series.

Background: The Epstein-Barr virus-associated natural killer (NK) and T-cell lymphoma (EBV + NK/T cell lymphoma) is a severe illness mainly affecting children and young adults, often resulting in a poor prognosis. To date, there is no consensus on an established treatment strategy. This study aims to evaluate the efficacy and safety of the mSMILE (modified steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide) chemotherapy regimen in treating EBV+ NK/T-cell lymphoma and to provide insights into potential treatment outcomes. Methods: In this study, we conducted a retrospective analysis of the clinical data and treatment outcomes for patients with EBV + NK/T cell lymphoma treated at Children's Hospital of Nanjing Medical University between July 2017 and January 2022. These patients received at least two cycles of the mSMILE chemotherapy, in which a single dose of pegaspargase was substituted for 7 doses of L-asparaginase per cycle. Results: Eight patients were included in the study: one with extranodal NK/T-cell lymphoma, one with primary nodal NK/T-cell lymphoma, and six with Systemic EBV+ NK/T cell lymphoma of childhood. The results showed that five patients achieved complete remission, two achieved partial remission, and one showed progressive disease, resulting in a complete remission rate of 62.5% and an overall response rate of 87.5%. The 3-year overall survival (OS) and event-free survival (EFS) rates were 87.5% and 75%, respectively. The most common adverse reactions associated with chemotherapy were hematologic toxicities of stages III to IV. Nonhematologic adverse reactions mainly included impaired liver function, infections, and oral mucositis, which were resolved with aggressive anti-infective therapy. Conclusions: Based on our clinical experience, the mSMILE appears to be a safe and effective treatment option for EBV + NK/T-cell lymphoma, meriting further investigation in late-phase clinical trials.

Integrative analysis of the ovarian metabolome and transcriptome of the Yaoshan chicken and its improved hybrids.

Introduction: Laying performance is a key factor affecting production efficiency in poultry, but its molecular mechanism is still indistinct. In this study, Yaoshan chickens, a local breed in Guizhou, China, and merchant chickens (GYR) with higher egg yield after the three-line cross improvement hybridization of Yaoshan chickens were used as animal samples. Methods: To explore the regulatory mechanism of the diversities in laying performance, RNA-seq and ultra-performance liquid chromatographytandem mass spectrometry (UPLC-MS/MS) were used to describe the transcriptional and metabolic profiles of the ovaries of Yaoshan and GYR chickens. Results: At the transcriptional level, 288 differentially expressed genes were upregulated in Yaoshan chickens and 353 differentially expressed genes were upregulated in GYR chickens. In addition, GSEA showed that ECM-receptor interactions and the TGF-ß signaling pathway were restrained, resulting in increased egg production in GYR chickens. Furthermore, the upregulation of thiamine and carnitine was identified by metabolomic analysis to facilitate the laying performance of hens. Finally, comprehensive analyses of the transcriptome and metabolome found that thiamine and carnitine were negatively correlated with ECM-receptor interactions and the TGF-ß signaling pathway, which jointly regulate the laying performance of Yaoshan chickens and GYR chickens. Discussion: Taken together, our research delineates differences in the transcriptional and metabolic profiles of the ovaries of Yaoshan and GYR chickens during the peak egg production period and provides new hypotheses and clues for further research on poultry egg production performance and the improvement of economic benefits.