Development of a Novel Prediction Tool for Response to First-Line Treatments of Monosymptomatic Nocturnal Enuresis-A Randomized, Controlled International Multicenter Study (DRYCHILD).

PURPOSE: Nocturnal urine volume and bladder reservoir function are key pathogenic factors behind monosymptomatic nocturnal enuresis (MNE). We investigated the predictive value of these together with other demographic and clinical variables for response to first-line treatments in children with MNE. MATERIALS AND METHODS: A randomized, controlled, international multicenter study was conducted in 324 treatment-naïve children (6-14 years) with primary MNE. The children were randomized to treatment with or without prior consideration of voiding diaries. In the group where treatment choice was based on voiding diaries, children with nocturnal polyuria and normal maximum voided volume (MVV) received desmopressin (dDAVP) treatment and children with reduced MVV and no nocturnal polyuria received an enuresis alarm. In the other group, treatment with dDAVP or alarm was randomly allocated. RESULTS: A total of 281 children (72% males) were qualified for statistical analysis. The change of responding to treatment was 21% higher in children where treatment was individualized compared to children where treatment was randomly selected (RR = 1.21 (1.02-1.45), P = .032). In children with reduced MVV and no nocturnal polyuria (35% of all children), individualized treatment was associated with a 46% improvement in response compared to random treatment selection (RR = 1.46 (1.14-1.87), P = .003). Furthermore, we developed a clinically relevant prediction model for response to dDAVP treatment (ROC 0.85). CONCLUSIONS: The present study demonstrates that treatment selection based on voiding diaries improve response to first line treatment, particularly in specific subtypes. Information from voiding diaries together with clinical and demographic information provides the basis for predicting response.

Analytical and experimental analysis of concrete temperature and energy considering open-air environmental variations.

Longwave radiation is an important open-air environmental factor that can significantly affect the temperature of concrete, but it has often been ignored in the temperature analysis of open-air concrete structures. In this article, an improved analytical model of concrete temperature was proposed by considering solar radiation, thermal convection, thermal conduction and especially longwave radiation. Temperature monitoring of an open-air concrete block was carried out to verify the proposed model and analyze the heat energy characteristics of open-air concrete. As demonstrated by the open-air experiment, under the influence of longwave radiation, the temperature at the top of the concrete block could decrease rapidly at night and even become lower than the minimum temperature at its bottom. Compared with the analytical model that ignores longwave radiation, the improved model that includes it better matches the measured temperature. According to the energy analysis, although solar radiation controls the transient variation in heat energy, the heat exchange caused by longwave radiation were more than that caused by convection on sunlit surfaces, which indicates the importance of considering longwave radiation.

Epidemiological exploration of the impact of bluetooth headset usage on thyroid nodules using Shapley additive explanations method.

With an increasing prevalence of thyroid nodules globally, this study investigates the potential correlation between the use of Bluetooth headsets and the incidence of thyroid nodules, considering the cumulative effects of non-ionizing radiation (NIR) emitted by these devices. In this study, we analyzed 600 valid questionnaires from the WenJuanXing platform using Propensity Score Matching (PSM) and the XGBOOST model, supplemented by SHAP analysis, to assess the risk of thyroid nodules. PSM was utilized to balance baseline characteristic differences, thereby reducing bias. The XGBOOST model was then employed to predict risk factors, with model efficacy measured by the area under the Receiver Operating Characteristic (ROC) curve (AUC). SHAP analysis helped quantify and explain the impact of each feature on the prediction outcomes, identifying key risk factors. Initially, 600 valid questionnaires from the WenJuanXing platform underwent PSM processing, resulting in a matched dataset of 96 cases for modeling analysis. The AUC value of the XGBOOST model reached 0.95, demonstrating high accuracy in differentiating thyroid nodule risks. SHAP analysis revealed age and daily Bluetooth headset usage duration as the two most significant factors affecting thyroid nodule risk. Specifically, longer daily usage durations of Bluetooth headsets were strongly linked to an increased risk of developing thyroid nodules, as indicated by the SHAP analysis outcomes. Our study highlighted a significant impact relationship between prolonged Bluetooth headset use and increased thyroid nodule risk, emphasizing the importance of considering health impacts in the use of modern technology, especially for devices like Bluetooth headsets that are frequently used daily. Through precise model predictions and variable importance analysis, our research provides a scientific basis for the formulation of public health policies and personal health habit choices, suggesting that attention should be paid to the duration of Bluetooth headset use in daily life to reduce the potential risk of thyroid nodules. Future research should further investigate the biological mechanisms of this relationship and consider additional potential influencing factors to offer more comprehensive health guidance and preventive measures.

Mechanism-Guided Computational Design Drives meso-Diaminopimelate Dehydrogenase to Efficient Synthesis of Aromatic d-amino Acids.

Aromatic d-amino acids (d-AAs) play a pivotal role as important chiral building blocks and key intermediates in fine chemical and drug synthesis. Meso-diaminopimelate dehydrogenase (DAPDH) serves as an excellent biocatalyst in the synthesis of d-AAs and their derivatives. However, its strict substrate specificity and the lack of efficient engineering methods have hindered its widespread application. Therefore, this study aims to elucidate the catalytic mechanism underlying DAPDH from Proteus vulgaris (PvDAPDH) through the examination of its crystallographic structure, computational simulations of potential energies and molecular dynamics simulations, and site-directed mutagenesis. Mechanism-guided computational design showed that the optimal mutant PvDAPDH-M3 increased specific activity and catalytic efficiency (kcat/Km) for aromatic keto acids up to 124-fold and 92.4-fold, respectively, compared to that of the wild type. Additionally, it expanded the substrate scope to 10 aromatic keto acid substrates. Finally, six high-value-added aromatic d-AAs and their derivatives were synthesized using a one-pot three-enzyme cascade reaction, exhibiting a good conversion rate ranging from 32 to 84% and excellent stereoselectivity (enantiomeric excess >99%). These findings provide a potential synthetic pathway for the green industrial production of aromatic d-AAs.

Extracellular Water Ratio and Phase Angle as Predictors of Exacerbation in Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD), characterized by high-energy metabolism, often leads to malnutrition and is linked to exacerbations. This study investigates the association of malnutrition-related body composition and handgrip strength changes with exacerbation frequencies in COPD patients. METHODS: We analyzed 77 acute exacerbation COPD (AECOPD) patients and 82 stable COPD patients, categorized as frequent and infrequent exacerbators. Assessments included body composition, handgrip strength, nutritional risk, dyspnea scale, and COPD assessment. RESULTS: Among AECOPD patients, there were 22 infrequent and 55 frequent exacerbators. Infrequent exacerbators showed better muscle parameters, extracellular water ratio, phase angle, and handgrip strength. Significant differences in intracellular water, total cellular water, protein, and body cell mass were observed between groups. Logistic regression indicated that extracellular water ratio (OR = 1.086) and phase angle (OR = 0.396) were independently associated with exacerbation risk. Thresholds for exacerbation risk were identified as 0.393 for extracellular water ratio and 4.85° for phase angle. In stable COPD, 13 frequent and 69 infrequent exacerbators were compared, showing no significant differences in weight, muscle, and adipose parameters, but significant differences in extracellular water ratio, phase angle, and handgrip strength. CONCLUSIONS: These findings suggest that increased exacerbations in COPD patients correlate with higher extracellular water ratios and lower phase angles.

Community Incidence Estimates of Five Pathogens Based on Foodborne Diseases Active Surveillance - China, 2023.

What is already known about this topic?: Foodborne diseases, representing significant food safety and public health challenges globally, are not well-documented in terms of incidence, particularly for cases characterized by acute gastroenteritis (AGI) in China. What is added by this report?: This study developed a pyramid model to estimate the incidence of five pathogens, stratified by gender and age. The estimated incidences per 100,000 people with 95% uncertainty intervals (UI) are as follows: Norovirus, 3,188.28 (95% UI: 2,518.03, 7,296.96); Salmonella spp., 1,295.59 (95% UI: 1,002.62, 1,573.11); diarrheagenic E. coli (DEC), 782.62 (95% UI: 651.19, 932.05); Vibrio parahaemolyticus, 404.06 (95% UI: 342.19, 468.93); and Shigella spp., 26.73 (95% UI: 21.05, 33.46). What are the implications for public health practice?: This study elucidates the incidence rates across various gender and age groups, thereby identifying priority populations for targeted preventive interventions aimed at reducing disease burden. These insights are crucial for the development of public health policies and management of food safety risks.

The prognostic value of ubiquitin/ubiquitin-like-related genes along with immune cell infiltration and clinicopathological features in osteosarcoma.

BACKGROUND: Ubiquitin/ubiquitin-like (Ub/UBL)-related genes have been reported to be associated with the survival of osteosarcoma patients but have not yet been systematically explored. METHODS: The prognostic value of Ub/UBL-related genes, immune cell infiltration and clinicopathological features of patients were explored by Cox and LASSO regression analyses. A prognostic model was established and then validated in the GSE21257 dataset. The differential expression of hub genes in osteosarcoma was confirmed by qRT-PCR, western blotting and immunohistochemistry. RESULTS: Tripartite Motif Containing 8 (TRIM8) and Ubiquitin Like With PHD And Ring Finger Domains 2 (UHRF2) were screened as genes with prognostic value in osteosarcoma. Kaplan-Meier analysis and scatter plots indicated that patients in the high gene significance score group tended to have a worse prognosis. The concordance index, calibration analysis and receiver operating characteristic analysis suggested that the model had good prediction accuracy and high sensitivity and specificity. Decision curve analysis revealed that patients could obtain greater net benefit from this model. Functional analyses of the differentially expressed genes indicated that they were involved in important functions and pathways. TRIM8 and UHRF2 were confirmed to be highly expressed in osteosarcoma cell lines and tissues. CONCLUSIONS: TRIM8 and UHRF2 are potential prognostic genes in osteosarcoma, and these results provide insights into the roles of these genes and their implications for patient outcomes.

Pleural carbohydrate antigen 50 and malignant pleural effusion: a prospective, double-blind diagnostic accuracy test.

Background: Serum carbohydrate antigen 50 (CA50) is an auxiliary diagnostic marker for various solid tumors, but it remains unclear whether CA50 in pleural fluid can assist in the diagnosis of malignant pleural effusion (MPE). This study aimed to evaluate the diagnostic accuracy of pleural fluid CA50 for MPE in pleural effusion patients with undetermined causes. Methods: This study prospectively recruited pleural effusion patients with undetermined causes who visited the Affiliated Hospital of Inner Mongolia Medical University between September 2018 and July 2021. We measured pleural fluid CA50 level with an electrochemiluminescence assay. We analyzed the diagnostic accuracy of CA50 and carcinoembryonic antigen (CEA) for MPE with the receiver operating characteristic (ROC) curve. The net benefits of CA50 and CEA were analyzed using the decision curve analysis (DCA). Results: We enrolled 66 MPEs and 87 benign pleural effusions (BPEs). MPE patients had significantly higher CA50 and CEA than BPE patients. The area under the ROC curve (AUC) of CA50 was 0.72 (95% CI: 0.63-0.80). CA50 had a sensitivity of 0.30 (95% CI: 0.19-0.41) and a specificity of 1.00 (95% CI: 1.00-1.00) at the threshold of 15 IU/mL. The decision curve of CA50 was above the reference line at the calculated risk probability of between 0.30 and 1.00. Venn diagram indicated that some patients with low CEA (<50 or <150 ng/mL) and/or negative cytology can be identified by positive CA50 (>15 IU/mL). Conclusions: Pleural fluid CA50 has moderate accuracy and net benefit for detecting MPE. CA50 >15 IU/mL can be used to diagnose MPE. The combination of CA50 and CEA improves the diagnostic sensitivity for MPE.

Diagnosis and treatment status of inoperable locally advanced breast cancer and the application value of inorganic nanomaterials.

Locally advanced breast cancer (LABC) is a heterogeneous group of breast cancer that accounts for 10-30% of breast cancer cases. Despite the ongoing development of current treatment methods, LABC remains a severe and complex public health concern around the world, thus prompting the urgent requirement for innovative diagnosis and treatment strategies. The primary treatment challenges are inoperable clinical status and ineffective local control methods. With the rapid advancement of nanotechnology, inorganic nanoparticles (INPs) exhibit a potential application prospect in diagnosing and treating breast cancer. Due to the unique inherent characteristics of INPs, different functions can be performed via appropriate modifications and constructions, thus making them suitable for different imaging technology strategies and treatment schemes. INPs can improve the efficacy of conventional local radiotherapy treatment. In the face of inoperable LABC, INPs have proposed new local therapeutic methods and fostered the evolution of novel strategies such as photothermal and photodynamic therapy, magnetothermal therapy, sonodynamic therapy, and multifunctional inorganic nanoplatform. This article reviews the advances of INPs in local accurate imaging and breast cancer treatment and offers insights to overcome the existing clinical difficulties in LABC management.

Stem cell division and its critical role in mammary gland development and tumorigenesis: current progress and remaining challenges.

The origin of breast cancer (BC) has traditionally been a focus of medical research. It is widely acknowledged that BC originates from immortal mammary stem cells (MaSCs) and that these stem cells participate in two division modes: symmetric cell division (SCD) and asymmetric cell division (ACD). Although both of these modes are key to the process of breast development and their imbalance is closely associated with the onset of BC, the molecular mechanisms underlying these phenomena deserve in-depth exploration. In this review, we first outline the molecular mechanisms governing ACD/SCD and analyze the role of ACD/SCD in various stages of breast development. We describe that the changes in telomerase activity, the role of polar proteins, and the stimulation of ovarian hormones subsequently lead to two distinct consequences: breast development or carcinogenesis. Finally, gene mutations, abnormalities in polar proteins, modulation of signal-transduction pathways, and alterations in the microenvironment disrupt the balance of breast cancer stem cells (BCSCs) division modes and cause BC. Important regulatory factors such as mammalian Inscuteable (mInsc), Numb, Eya1, PKCα, PKCθ, p53, and IL-6 also play significant roles in regulating pathways of ACD/SCD and may constitute key targets for future research on stem cell division, breast development, and tumor therapy.

Rational Design of the Spatial Effect in a Fe(II)/α-Ketoglutarate-Dependent Dioxygenase Reverses the Regioselectivity of C(sp3)-H Bond Hydroxylation in Aliphatic Amino Acids.

The hydroxylation of remote C(sp3)-H bonds in aliphatic amino acids yields crucial precursors for the synthesis of high-value compounds. However, accurate regulation of the regioselectivity of remote C(sp3)-H bonds hydroxylation in aliphatic amino acids continues to be a common challenge in chemosynthesis and biosynthesis. In this study, the Fe(II)/α-ketoglutarate-dependent dioxygenase from Bacillus subtilis (BlAH) was mined and found to catalyze hydroxylation at the γ and δ sites of aliphatic amino acids. Crystal structure analysis, molecular dynamics simulations, and quantum chemical calculations revealed that regioselectivity was regulated by the spatial effect of BlAH. Based on these results, the spatial effect of BlAH was reconstructed to stabilize the transition state at the δ site of aliphatic amino acids, thereby successfully reversing the γ site regioselectivity to the δ site. For example, the regioselectivity of L-Homoleucine (5 a) was reversed from the γ site (1 : 12) to the δ site (>99 : 1). The present study not only expands the toolbox of biocatalysts for the regioselective functionalization of remote C(sp3)-H bonds, but also provides a theoretical guidance for the precision-driven modification of similarly remote C(sp3)-H bonds in complex molecules.

The Impact of Predation Risks on the Development and Fecundity of Bactrocera dorsalis Hendel.

Predators are dependent on the capture of prey to meet their energetic and nutritive requirements, which brings the risk of predation to prey. The predation risk is divided into consumptive and non-consumptive effects. Non-consumptive effects may manifest through altered growth and ontogenetic trajectories in prey species, a dynamic modulated by olfactory or other sensory cues from predators. Bactrocera dorsalis Hendel represents a major invasive threat to global horticulture. While earlier research was primarily centered on the consumptive interactions between B. dorsalis and its natural enemies, the potential consequences of non-consumptive interactions on the development of B. dorsalis have been overlooked. In this study, we investigated the impact of predation risk effects, induced by both visual exposure to the predatory mantis Hierodula patellifera Serville and its associated odor, on the life history traits of B. dorsalis. Female B. dorsalis demonstrated a reduced developmental time in the presence of a caged predator (H. patellifera) or predator odors, but showed significantly increased fecundity. Conversely, males displayed no significant change in developmental time. Additionally, neither the female nor male body weight at death was significantly influenced by the predation risk from the caged predator or predator odors. This study investigated the effects of predation risk on the development and reproduction of B. dorsalis, emphasizing the potential importance of odor risk in biological and pest control.

Intermittent sliding-lock-knot suture for limbal conjunctival autograft fixation in pterygium surgery: a technique note.

AIM: To report a technique used with intermittent sliding-lock-knot (ISLK) fixation for limbal conjunctival autografts in pterygium surgery and compared with those of routine intermittent (RI) fixation. METHODS: Consecutive patients with primary pterygium who had undergone pterygium excision combined with limbal conjunctival autograft transplantation between March 2021 and March 2022 at our institute were retrospectively analyzed. Primary outcome measures were mean duration of surgery and suture removal, degree of conjunctival hyperemia on postoperative day 1, pain score at suture removal, postoperative symptoms at 6mo, including conjunctival hyperemia, foreign body sensation, and graft stability. RESULTS: Ninety-eight patients underwent monocular surgery and were divided into ISLK (51 eyes) and RI (47 eyes) groups according to the type of conjunctiva autograft fixation method planned. There was no significant difference in mean duration of surgery between the two groups (18.59±2.39min vs 18.15±2.20min, P=0.417); however, compared to the RI group, shorter suture removal times were observed in the ISLK group [0.58min (0.42-0.87) vs 3.00min (2.21-4.15), P<0.001]. The degree of conjunctival hyperemia on postoperative day 1 was milder in the ISLK group (P<0.001). Pain scores at suture removal were lower in the ISLK group than in RI group [1 (0-3) vs 2 (1-4), P<0.001]. Postoperative symptoms at 6mo were comparable between the groups (P=0.487), with no recurrence. CONCLUSION: ISLK is an innovative method for limbal conjunctival autograft fixation after pterygium excision. Compared to RI fixation, ISLK facilitates suture removal and reduces discomfort, with comparable surgery duration and less conjunctival hyperemia.

Identifying the risk factors of ICU-acquired fungal infections: clinical evidence from using machine learning.

Background: Fungal infections are associated with high morbidity and mortality in the intensive care unit (ICU), but their diagnosis is difficult. In this study, machine learning was applied to design and define the predictive model of ICU-acquired fungi (ICU-AF) in the early stage of fungal infections using Random Forest. Objectives: This study aimed to provide evidence for the early warning and management of fungal infections. Methods: We analyzed the data of patients with culture-positive fungi during their admission to seven ICUs of the First Affiliated Hospital of Chongqing Medical University from January 1, 2015, to December 31, 2019. Patients whose first culture was positive for fungi longer than 48 h after ICU admission were included in the ICU-AF cohort. A predictive model of ICU-AF was obtained using the Least Absolute Shrinkage and Selection Operator and machine learning, and the relationship between the features within the model and the disease severity and mortality of patients was analyzed. Finally, the relationships between the ICU-AF model, antifungal therapy and empirical antifungal therapy were analyzed. Results: A total of 1,434 cases were included finally. We used lasso dimensionality reduction for all features and selected six features with importance ≥0.05 in the optimal model, namely, times of arterial catheter, enteral nutrition, corticosteroids, broadspectrum antibiotics, urinary catheter, and invasive mechanical ventilation. The area under the curve of the model for predicting ICU-AF was 0.981 in the test set, with a sensitivity of 0.960 and specificity of 0.990. The times of arterial catheter (p = 0.011, OR = 1.057, 95% CI = 1.053-1.104) and invasive mechanical ventilation (p = 0.007, OR = 1.056, 95%CI = 1.015-1.098) were independent risk factors for antifungal therapy in ICU-AF. The times of arterial catheter (p = 0.004, OR = 1.098, 95%CI = 0.855-0.970) were an independent risk factor for empirical antifungal therapy. Conclusion: The most important risk factors for ICU-AF are the six time-related features of clinical parameters (arterial catheter, enteral nutrition, corticosteroids, broadspectrum antibiotics, urinary catheter, and invasive mechanical ventilation), which provide early warning for the occurrence of fungal infection. Furthermore, this model can help ICU physicians to assess whether empiric antifungal therapy should be administered to ICU patients who are susceptible to fungal infections.

Rational design improves both thermostability and activity of a new D-tagatose 3-epimerase from Kroppenstedtia eburnean to produce D-allulose.

D-allulose is a naturally occurring rare sugar and beneficial to human health. However, the efficient biosynthesis of D-allulose remains a challenge. Here, we mined a new D-tagatose 3-epimerase from Kroppenstedtia eburnean (KeDt3e) with high catalytic efficiency. Initially, crucial factors contributing to the low conversion of KeDt3e were identified through crystal structure analysis, density functional theory calculations (DFT), and molecular dynamics (MD) simulations. Subsequently, based on the mechanism, combining restructuring the flexible region, proline substitution based onconsensus sequence analysis, introducing disulfide bonds, and grafting properties, and reshaping the active center, the optimal mutant M5 of KeDt3e was obtained with enhanced thermostability and activity. The optimal mutant M5 exhibited an enzyme activity of 130.8 U/mg, representing a 1.2-fold increase; Tm value increased from 52.7 °C to 71.2 °C; and half-life at 55 °C extended to 273.7 min, representing a 58.2-fold improvement, and the detailed mechanism of performance improvement was analyzed. Finally, by screening the ribosome-binding site (RBS) of the optimal mutant M5 recombinant bacterium (G01), the engineered strain G08 with higher expression levels was obtained. The engineered strain G08 catalyzed 500 g/L D-fructose to produce 172.4 g/L D-allulose, with a conversion of 34.4% in 0.5 h and productivity of 344.8 g/L/h on a 1 L scale. This study presents a promising approach for industrial-scale production of D-allulose.

Diagnostic accuracy and cellular origin of pleural fluid CXCR3 ligands for tuberculous pleural effusion.

BACKGROUND: Pleural biomarkers represent potential diagnostic tools for tuberculous pleural effusion (TPE) due to their advantages of low cost, short turnaround time, and less invasiveness. This study evaluated the diagnostic accuracy of two CXCR3 ligands, C-X-C motif chemokine ligand 9 (CXCL9) and CXCL11, for TPE. In addition, we investigated the cellular origins and biological roles of CXCL9 and CXCL11 in the development of TPE. METHODS: This double-blind study prospectively enrolled patients with undiagnosed pleural effusion from two centers (Hohhot and Changshu) in China. Pleural fluid on admission was obtained and levels of CXCL9 and CXCL11 were measured by an enzyme-linked immunosorbent assay (ELISA). The receiver operating characteristic (ROC) curve and the decision curve analysis (DCA) were used to evaluate their diagnostic accuracy and net benefit, respectively. THP-1 cell-derived macrophages were treated with Bacillus Calmette-Guérin (BCG), and quantitative real-time PCR (qRT-PCR) and ELISA were used to determine the mRNA and protein levels of CXCL9 and CXCL11. The chemoattractant activities of CXCL9 and CXCL11 for T helper (Th) cells were analyzed by a transwell assay. RESULTS: One hundred and fifty-three (20 TPEs and 133 non-TPEs) patients were enrolled in the Hohhot Center, and 58 (13 TPEs and 45 non-TPEs) were enrolled in the Changshu Center. In both centers, we observed increased CXCL9 and CXCL11 in TPE patients. The areas under the ROC curves (AUCs) of pleural CXCL9 and CXCL11 in the Hohhot Center were 0.70 (95 % CI: 0.55-0.85) and 0.68 (95 % CI: 0.52-0.84), respectively. In the Changshu Center, the AUCs of CXCL9 and CXCL11 were 0.96 (95 % CI: 0.92-1.00) and 0.97 (95 % CI: 0.94-1.00), respectively. The AUCs of CXCL9 and CXCL11 decreased with the advancement of age. The decision curves of CXCL9 and CXCL11 showed net benefits in both centers. CXCL9 and CXCL11 were upregulated in BCG-treated macrophages. Pleural fluid from TPE and conditioned medium from BCG-treated macrophages were chemotactic for Th cells. Anti-CXCL9 or CXCL11 neutralizing antibodies could partly block the chemotactic activity. CONCLUSIONS: Pleural CXCL9 and CXCL11 are potential diagnostic markers for TPE, but their diagnostic accuracy is compromised in elderly patients. CXCL9 and CXCL11 can promote the migration of peripheral Th cells, thus representing a therapeutic target for the treatment of TPE.

Four sulfur-containing compounds with anti-colon cancer effect from marine-derived fungus Aspergillus terreus.

Sulfur-containing natural products possess a variety of biological functions including antitumor, antibacterial, anti-inflammatory and antiviral activities. In this study, four previously undescribed sulfur-containing compounds asperteretals L and M, terreins A and B, together with 17 known compounds were obtained from a culture of marine fungus A. terreus supplemented with inorganic sulfur source Na2SO4. Their planar structures and absolute configurations were elucidated by NMR, HRESIMS, and ECD experiments. The in vitro cytotoxicities of compounds 1-21 against HCT-116 and Caco-2 were evaluated by SRB assay. Asperteretal M (2) exhibited activity against HCT-116 with the IC50 value at 30µM. The antiproliferative effect of asperteretal M was confirmed by colony formation assay and cell death staining. Furthermore, the preliminary study on the anti-colon cancer mechanism of asperteretal M was performed by RNA-seq analysis. Western blotting validated that asperteretal M significantly decreased the expression of cell-cycle regulatory proteins CDK1, CDK4, and PCNA in a concentration-dependent manner.

Rational Design of Salmonella typhi Acid Phosphatase for Efficient Production of Pyridoxal 5'-Phosphate.

Pyridoxal 5'-phosphate (PLP) is highly valuable in food and medicine. However, achieving the efficient biosynthesis of PLP remains challenging. Here, a salvage pathway using acid phosphatase from Salmonella typhi (StAPase) and pyridoxine oxidase from Escherichia coli (EcPNPO) as pathway enzymes was established for the first time to synthesize PLP from pyridoxine (PN) and pyrophosphate (PPi). StAPase was identified as a rate-limiting enzyme. Two protein modification strategies were developed based on the PN phosphorylation mechanism: (1) improving the binding of PN into StAPase and (2) enhancing the hydrophobicity of StAPase's substrate binding pocket. The kcat/Km of optimal mutant M7 was 4.9 times higher than that of the wild type. The detailed mechanism of performance improvement was analyzed. Under the catalysis of M7 and EcPNPO, a PLP high-yielding strain of 14.5 ± 0.55 g/L was engineered with a productivity of 1.0 ± 0.02 g/(L h) (the highest to date). The study suggests a promising method for industrial-scale PLP production.

Glucose regulation of adipose tissue browning by CBP/p300- and HDAC3-mediated reversible acetylation of CREBZF.

Glucose is required for generating heat during cold-induced nonshivering thermogenesis in adipose tissue, but the regulatory mechanism is largely unknown. CREBZF has emerged as a critical mechanism for metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD). We investigated the roles of CREBZF in the control of thermogenesis and energy metabolism. Glucose induces CREBZF in human white adipose tissue (WAT) and inguinal WAT (iWAT) in mice. Lys208 acetylation modulated by transacetylase CREB-binding protein/p300 and deacetylase HDAC3 is required for glucose-induced reduction of proteasomal degradation and augmentation of protein stability of CREBZF. Glucose induces rectal temperature and thermogenesis in white adipose of control mice, which is further potentiated in adipose-specific CREBZF knockout (CREBZF FKO) mice. During cold exposure, CREBZF FKO mice display enhanced thermogenic gene expression, browning of iWAT, and adaptive thermogenesis. CREBZF associates with PGC-1α to repress thermogenic gene expression. Expression levels of CREBZF are negatively correlated with UCP1 in human adipose tissues and increased in WAT of obese ob/ob mice, which may underscore the potential role of CREBZF in the development of compromised thermogenic capability under hyperglycemic conditions. Our results reveal an important mechanism of glucose sensing and thermogenic inactivation through reversible acetylation.

Whole-Genome Sequencing Analyses Reveal the Evolution Mechanisms of Typical Biological Features of Decapterus maruadsi.

Decapterus maruadsi is a typical representative of small pelagic fish characterized by fast growth rate, small body size, and high fecundity. It is a high-quality marine commercial fish with high nutritional value. However, the underlying genetics and genomics research focused on D. maruadsi is not comprehensive. Herein, a high-quality chromosome-level genome of a male D. maruadsi was assembled. The assembled genome length was 716.13 Mb with contig N50 of 19.70 Mb. Notably, we successfully anchored 95.73% contig sequences into 23 chromosomes with a total length of 685.54 Mb and a scaffold N50 of 30.77 Mb. A total of 22,716 protein-coding genes, 274.90 Mb repeat sequences, and 10,060 ncRNAs were predicted, among which 22,037 (97%) genes were successfully functionally annotated. The comparative genome analysis identified 459 unique, 73 expanded, and 52 contracted gene families. Moreover, 2804 genes were identified as candidates for positive selection, of which some that were related to the growth and development of bone, muscle, cardioid, and ovaries, such as some members of the TGF-ß superfamily, were likely involved in the evolution of typical biological features in D. maruadsi. The study provides an accurate and complete chromosome-level reference genome for further genetic conservation, genomic-assisted breeding, and adaptive evolution research for D. maruadsi.