Characterization of Metabolic Patterns in Mouse Oocytes during Meiotic Maturation.

Well-balanced and timed metabolism is essential for making a high-quality egg. However, the metabolic framework that supports oocyte development remains poorly understood. Here, we obtained the temporal metabolome profiles of mouse oocytes during in vivo maturation by isolating large number of cells at key stages. In parallel, quantitative proteomic analyses were conducted to bolster the metabolomic data, synergistically depicting the global metabolic patterns in oocytes. In particular, we discovered the metabolic features during meiotic maturation, such as the fall in polyunsaturated fatty acids (PUFAs) level and the active serine-glycine-one-carbon (SGOC) pathway. Using functional approaches, we further identified the key targets mediating the action of PUFA arachidonic acid (ARA) on meiotic maturation and demonstrated the control of epigenetic marks in maturing oocytes by SGOC network. Our data serve as a broad resource on the dynamics occurring in metabolome and proteome during oocyte maturation.

Proteomic Profiling Reveals the Molecular Control of Oocyte Maturation.

Meiotic maturation is an intricate and precisely regulated process orchestrated by various pathways and numerous proteins. However, little is known about the proteome landscape during oocytes maturation. Here, we obtained the temporal proteomic profiles of mouse oocytes during in vivo maturation. We successfully quantified 4694 proteins from 4500 oocytes in three key stages (germinal vesicle, germinal vesicle breakdown, and metaphase II). In particular, we discovered the novel proteomic features during oocyte maturation, such as the active Skp1-Cullin-Fbox pathway and an increase in mRNA decay-related proteins. Using functional approaches, we further identified the key factors controlling the histone acetylation state in oocytes and the vital proteins modulating meiotic cell cycle. Taken together, our data serve as a broad resource on the dynamics occurring in oocyte proteome and provide important knowledge to better understand the molecular mechanisms during germ cell development.

Injectable Nanocomposite Immune Hydrogel Dressings: Prevention of Tumor Recurrence and Anti-Infection after Melanoma Resection.

Complex wound repair due to tumor recurrence and infection following tumor resection presents significant clinical challenges. In this study, a bifunctional nanocomposite immune hydrogel dressing, SerMA-LJC, is developed to address the issues associated with repairing infected damaged tissues and preventing tumor recurrence. Specifically, the immune dressing is composed of methacrylic anhydride-modified sericin (SerMA) and self-assembled nanoparticles (LJC) containing lonidamine (Lon), JQ1, and chlorine e6 (Ce6). In vitro and in vivo experiments demonstrate that the nanocomposite hydrogel dressing can trigger immunogenic cell death (ICD) and has a potent anti-tumor effect. Moreover, this dressing can mitigate the acidic microenvironment of tumor cells and suppress the overexpression of PD-L1 on the tumor cell surface, thereby altering the immunosuppressive tumor microenvironment and augmenting the anti-tumor immune response. Further, the RNA sequencing analysis revealed that the hydrogel dressing significantly impacts pathways associated with positive regulation of immune response, apoptotic process, and other relevant pathways, thus triggering a potent anti-tumor immune response. More importantly, the dressing generates a substantial amount of reactive oxygen species (ROS), which can effectively kill Staphylococcus aureus and promote infectious wound healing. In conclusion, this dual-function nanocomposite immune hydrogel dressing exhibits promise in preventing tumor recurrence and promoting infectious wound healing.

Integrated genetic and epigenetic analyses uncovered GLP1R association with metabolically healthy obesity.

BACKGROUND: Both genetic and epigenetic variations of GLP1R influence the development and progression of obesity. However, the underlying mechanism remains elusive. This study aims to explore the mediation roles of obesity-related methylation sites in GLP1R gene variants-obesity association. METHODS: A total of 300 Chinese adult participants were included in this study and classified into two groups: 180 metabolically healthy obesity (MHO) cases and 120 metabolically healthy normal-weight (MHNW) controls. Questionnaire investigation, physical measurement and laboratory examination were assessed in all participants. 18 single nucleotide polymorphisms (SNPs) and 31 CpG sites were selected for genotype and methylation assays. Causal inference test (CIT) was performed to evaluate the associations between GLP1R genetic variation, DNA methylation and MHO. RESULTS: The study found that rs4714211 polymorphism of GLP1R gene was significantly associated with MHO. Additionally, methylation sites in the intronic region of GLP1R (GLP1R-68-CpG 7.8.9; GLP1R-68-CpG 12.13; GLP1R-68-CpG 17; GLP1R-68-CpG 21) were associated with MHO, and two of these methylation sites (GLP1R-68-CpG 7.8.9; GLP1R-68-CpG 17) partially mediated the association between genotypes and MHO. CONCLUSIONS: Not only the gene polymorphism, but also the DNA methylation of GLP1R was associated with MHO. Epigenetic changes in the methylome may in part explain the relationship between genetic variants and MHO.

Rational Design of CoOOH/α-Fe2O3/SnO2 for Boosted Photoelectrochemical Water Oxidation: The Roles of Underneath SnO2 and Surface CoOOH.

Hematite (α-Fe2O3) photoanode is a promising candidate for efficient PEC solar energy conversion. However, the serious charge recombination together with the sluggish water oxidation kinetics of α-Fe2O3 still restricts its practical application in renewable energy systems. In this work, a CoOOH/α-Fe2O3/SnO2 photoanode was fabricated, in which the ultrathin SnO2 underlayer is deposited on the fluorine-doped tin oxide (FTO) substrate, α-Fe2O3 nanorod array is the absorber layer, and CoOOH nanosheet is the surface modifier, respectively. The resulting CoOOH/α-Fe2O3/SnO2 exhibited excellent PEC water splitting with a high photocurrent density of 2.05 mA cm-2 at 1.23 V vs RHE in the alkaline electrolyte, which is ca. 3.25 times that of bare α-Fe2O3. PEC characterizations demonstrated that SnO2 not only could block hole transport from α-Fe2O3 to FTO substrate but also could efficiently enhance the light-harvesting property and reduce the surface states by controlling the growth process of α-Fe2O3, while the CoOOH overlayer as cocatalysts could rapidly extract the photogenerated holes and provide catalytic active sites for water oxidation. Benefiting from the synergistic effects of SnO2 and CoOOH, the efficiency of the charge recombination and the overpotential for water oxidation of α-Fe2O3 are obviously decreased, resulting in the boosted PEC efficiency for water oxidation. The rational design and simple fabrication strategy display great potentials to be used for other PEC systems with excellent efficiency.

Hypoxia promotes immune escape of pancreatic cancer cells by lncRNA NNT-AS1/METTL3-HuR-mediated ITGB1 m6A modification.

Pancreatic cancer (PC) cell immune escape is a crucial element in PC malignant development. Some previous studies have reported that LncRNA NNT-AS1 played a carcinogenic role in various tumors. However, the effect of lncRNA NNT-AS1 in PC cell immune escape remains unclear. To evaluate PC cell immune escape, PC cells were co-cultured with CD8+ T cells under a hypoxic condition. PC cell proliferation and migration were evaluated using the colony formation assay and transwell assay. CD8+ T cell proliferation and aoptosis were measured using the carboxy fluorescein diacetate succinimidyl ester (CFSE) assay and flow cytometry. The secretion of antitumor cytokines was assessed using enzyme-linked immunosorbent assay (ELISA). The molecular interactions were analyzed using chromatin immunoprecipitation (ChIP), RNA immunoprecipitation (RIP), or dual-luciferase reporter gene assays. A tumor xenograft model was established to evaluate the effects of lncRNA NNT-AS1 on PC in vivo. It was found that lncRNA NNT-AS1 was highly expressed in PC, and its silencing inhibited hypoxia-induced PC cell growth and immune escape in vivo and in vitro. Mechanically, HIF-1α transcriptionally activated NNT-AS1 expression and NNT-AS1 increased ITGB1 stability and expression in a METTL3-HuR dependent manner. ITGB1 overexpression reversed the inhibitory effects of NNT-AS1 knockdown on hypoxia-induced PC cell immune escape. In conclusion, Hypoxia promoted PC cell immune escape through lncRNA NNT-AS1/METTL3-HuR-mediated m6A modification to increase ITGB1 expression, which provided a theoretical foundation and a potential therapeutic target for PC.

Identifying the role of hypoxia-related lncRNAs in pancreatic cancer.

BACKGROUND: Long noncoding RNAs (lncRNAs) play important roles in hypoxia-induced tumor processes. However, the prognostic value of hypoxia-related lncRNAs in pancreatic cancer is limited. METHODS: Hypoxia-related lncRNAs were identified by coexpression analysis and the LncTarD database. LASSO analysis was performed to develop a prognostic model. The function of TSPOAP1-AS1 was studied in vitro and in vivo. RESULTS: We recognized a set of fourteen hypoxia-related lncRNAs for the construction of a prognostic model. The prognostic model displayed excellent performance in predicting the prognosis of pancreatic cancer patients. The overexpression of TSPOAP1-AS1, a hypoxia-related lncRNA, attenuated the proliferation and invasion of pancreatic cancer cells. HIF-1α bound to the promoter of TSPOAP1-AS1 and impaired its transcription under hypoxia. CONCLUSION: The hypoxia-related lncRNA assessment model might be a potential strategy for prognostic prediction in pancreatic cancer. The fourteen lncRNAs contained in the model could be helpful for uncovering the mechanisms of pancreatic tumorigenesis.

Functional outcomes of different surgical treatments for common peroneal nerve injuries: a retrospective comparative study.

BACKGROUND: This study aims to assess the recovery patterns and factors influencing outcomes in patients with common peroneal nerve (CPN) injury. METHODS: This retrospective study included 45 patients with CPN injuries treated between 2009 and 2019 in Jing'an District Central Hospital. The surgical interventions were categorized into three groups: neurolysis (group A; n = 34 patients), nerve repair (group B; n = 5 patients) and tendon transfer (group C; n = 6 patients). Preoperative and postoperative sensorimotor functions were evaluated using the British Medical Research Council grading system. The outcome of measures included the numeric rating scale, walking ability, numbness and satisfaction. Receiver operating characteristic (ROC) curve analysis was utilized to determine the optimal time interval between injury and surgery for predicting postoperative foot dorsiflexion function, toe dorsiflexion function, and sensory function. RESULTS: Surgical interventions led to improvements in foot dorsiflexion strength in all patient groups, enabling most to regain independent walking ability. Group A (underwent neurolysis) had significant sensory function restoration (P < 0.001), and three patients in Group B (underwent nerve repair) had sensory improvements. ROC analysis revealed that the optimal time interval for achieving M3 foot dorsiflexion recovery was 9.5 months, with an area under the curve (AUC) of 0.871 (95% CI = 0.661-1.000, P = 0.040). For M4 foot dorsiflexion recovery, the optimal cut-off was 5.5 months, with an AUC of 0.785 (95% CI = 0.575-0.995, P = 0.020). When using M3 toe dorsiflexion recovery or S4 sensory function recovery as the gold standard, the optimal cut-off remained at 5.5 months, with AUCs of 0.768 (95% CI = 0.582-0.953, P = 0.025) and 0.853 (95% CI = 0.693-1.000, P = 0.001), respectively. CONCLUSIONS: Our study highlights the importance of early surgical intervention in CPN injury recovery, with optimal outcomes achieved when surgery is performed within 5.5 to 9.5 months post-injury. These findings provide guidance for clinicians in tailoring treatment plans to the specific characteristics and requirements of CPN injury patients.

The Microtubule End Binding Protein Mal3 Is Essential for the Dynamic Assembly of Microtubules during Magnaporthe oryzae Growth and Pathogenesis.

Cytoskeletal microtubules (MTs) play crucial roles in many aspects of life processes in eukaryotic organisms. They dynamically assemble physiologically important MT arrays under different cell conditions. Currently, aspects of MT assembly underlying the development and pathogenesis of the model plant pathogenic fungus Magnaporthe oryzae (M. oryzae) are unclear. In this study, we characterized the MT plus end binding protein MoMal3 in M. oryzae. We found that knockout of MoMal3 results in defects in hyphal polar growth, appressorium-mediated host penetration and nucleus division. Using high-resolution live-cell imaging, we further found that the MoMal3 mutant assembled a rigid MT in parallel with the MT during hyphal polar growth, the cage-like network in the appressorium and the stick-like spindle in nuclear division. These aberrant MT organization patterns in the MoMal3 mutant impaired actin-based cell growth and host infection. Taken together, these findings showed that M. oryzae relies on MoMal3 to assemble elaborate MT arrays for growth and infection. The results also revealed the assembly mode of MTs in M. oryzae, indicating that MTs are pivotal for M. oryzae growth and host infection and may be new targets for devastating fungus control.

Anatomical study of the motor branches of the tibial nerve and incision design for hyperselective neurectomy.

PURPOSE: Selective tibial neurotomy (STN) is a surgical procedure for treating spastic equinovarus foot. Hyperselective neurectomy (HSN) of tibial nerve is a modified STN procedure, which was rarely discussed. This study aimed to describe the branching patterns of the tibial nerve and propose an optimal surgical incision of HSN for treatment of spastic equinovarus foot. METHODS: Sixteen lower limbs were dissected to determine the various branching patterns of the tibial nerve and categorized according to these branching patterns. The mean distances from the nerve entry points to the tip of femur's medial epicondyle were measured, as well as their percentage to the overall length of the leg. The surgical incision was designed according to the range of these nerve entry points. RESULTS: The tibial nerve sent out proximal and distal motor branches based on their position relative to the soleus muscle's tendinous arch. For proximal motor branches, the branches innervating the medial gastrocnemius, lateral gastrocnemius and proximal soleus were categorized into types I (9/16), II (5/16) and III (2/16). Measurements from the medial epicondyle to the nerve entry points into the medial gastrocnemius, lateral gastrocnemius and proximal soleus ranged from 14 to 33 mm (4-9% of leg length), 22-45 mm (6-12%) and 35-81 mm (10-22%), respectively. Distal motor branches including the distal soleus, posterior tibialis, flexor digitorum longus and flexor hallucis longus, were classified as types A (8/14), B (4/14) and C (2/14), with the distances from their respective terminal points to the medial epicondyle were 67-137 mm (19-39%), 74-125 mm (20-35%), 116-243 mm (33-69%) and 125-272 mm (35-77%). CONCLUSIONS: The motor branches of tibial nerve were classified into two groups and each subdivided into three types. Detailed location parameters may serve as an anatomical basis for designing incision of HSN.

Genome-wide DNA methylation analysis of body composition in Chinese monozygotic twins.

BACKGROUND: Little is currently known about epigenetic alterations associated with body composition in obesity. Thus, we aimed to explore epigenetic relationships between genome-wide DNA methylation levels and three common traits of body composition as measured by body fat percentage (BF%), fat mass (FM) and lean body mass (LBM) among Chinese monozygotic twins. METHODS: Generalized estimated equation model was used to regress the methylation level of CpG sites on body composition. Inference about Causation Through Examination Of Familial Confounding was used to explore the evidence of a causal relationship. Gene expression analysis was further performed to validate the results of differentially methylated genes. RESULTS: We identified 32, 22 and 28 differentially methylated CpG sites (p < 10-5 ) as well as 20, 17 and eight differentially methylated regions (slk-corrected p < 0.05) significantly associated with BF%, FM and LBM which were annotated to 65 genes, showing partially overlapping. Causal inference demonstrated bidirectional causality between DNA methylation and body composition (p < 0.05). Gene expression analysis revealed significant correlations between expression levels of five differentially methylated genes and body composition (p < 0.05). CONCLUSIONS: These DNA methylation signatures will contribute to increased knowledge about the epigenetic basis of body composition and provide new strategies for early prevention and treatment of obesity and its related diseases.

1-Indanone retards cyst development in ADPKD mouse model by stabilizing tubulin and down-regulating anterograde transport of cilia.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease. Cyst development in ADPKD involves abnormal epithelial cell proliferation, which is affected by the primary cilia-mediated signal transduction in the epithelial cells. Thus, primary cilium has been considered as a therapeutic target for ADPKD. Since ADPKD exhibits many pathological features similar to solid tumors, we investigated whether targeting primary cilia using anti-tumor agents could alleviate the development of ADPKD. Twenty-four natural compounds with anti-tumor activity were screened in MDCK cyst model, and 1-Indanone displayed notable inhibition on renal cyst growth without cytotoxicity. This compound also inhibited cyst development in embryonic kidney cyst model. In neonatal kidney-specific Pkd1 knockout mice, 1-Indanone remarkably slowed down kidney enlargement and cyst expansion. Furthermore, we demonstrated that 1-Indanone inhibited the abnormal elongation of cystic epithelial cilia by promoting tubulin polymerization and significantly down-regulating expression of anterograde transport motor protein KIF3A and IFT88. Moreover, we found that 1-Indanone significantly down-regulated ciliary coordinated Wnt/ß-catenin, Hedgehog signaling pathways. These results demonstrate that 1-Indanone inhibits cystic cell proliferation by reducing abnormally prolonged cilia length in cystic epithelial cells, suggesting that 1-Indanone may hold therapeutic potential to retard cyst development in ADPKD.

Dynamic perturbation analysis of fractional order differential quasiperiodic Mathieu equation.

The paper investigates the influence of parameters on the stability of fractional order differential quasiperiodic Mathieu equations. First, we use the perturbation method to obtain approximate expressions (i.e., transition curves) for the stability and unstable region boundaries of the equation. After obtaining the approximate expression of the transition curve, we use Lyapunov's first method to analyze the stability of the fractional order differential quasiperiodic Mathieu system, thereby obtaining the conditions for the stability of the fractional order differential quasiperiodic Mathieu equation system. Second, by comparing the approximate expressions of the transition curve of the steady-state periodic solution of the quasiperiodic Mathieu oscillator under different parameter conditions, we obtained the conclusion that the fractional order differential term exists in the form of equivalent stiffness and equivalent damping in the fractional order differential quasiperiodic Mathieu system. By comparison, we have summarized the general forms of equivalent linear damping and equivalent stiffness of the system. Through this general form, we can define an approximate expression for the thickness of unstable regions to better study the characteristics of fractional order differential quasiperiodic Mathieu systems. Finally, the influence of the parameters of the fractional order differential quasiperiodic Mathieu equation on the transition curve of the equation was intuitively analyzed through numerical simulation, to analyze the stability changes in the equation.

ent-Herqueidiketal and epi-Peniciherqueinone Isolated from a Mushroom Derived Fungus Penicillium herquei YNJ-35.

A new polyaromatic metabolite, ent-herqueidiketal (1), and a new phenalenone derivative, epi-peniciherqueinone (2), along with twelve known compounds 3-14, were isolated from the fungus Penicillium herquei YNJ-35, a symbiotic fungus of Pulveroboletus brunneopunctatus collected from Nangunhe Nature Reserve, Yunnan Province, China. The structures of 1-14 and the absolute configurations of 1 and 2 were determined by their spectroscopic data or by their single-crystal X-ray diffraction analysis or optical rotation values. Compound 1 showed strong antibacterial activity against Staphylococcus aureus (ATCC 29213) with minimum inhibitory concentration (MIC) of 8 µg/mL. In the cytotoxicity assays, compound 1 showed weak inhibitory activity against breast cancer MCF-7 and mice microglial BV2 cells with half maximal inhibitory concentration (IC50 ) of 17.58 and 29.56 µM; compound 14 showed stronger cytotoxicity against BV2 and MCF-7 cells with IC50 values of 6.57 and 10.26 µM.

Efficient removal of naphthenic acids from real petroleum wastewater by natural pyrite activated persulfate system.

The petroleum wastewater (PWW) contains a diverse range of recalcitrant organic contaminants. Of particular concern is the removal of naphthenic acids (NAs) due to the high toxicity and persistence. Persulfate (PS) based oxidation processes have shown promising in treating refractory wastewater, while the high costs of prepared catalysts limited their widespread implementation. This study aims to develop a cost-effective natural pyrite activated PS system for PWW treatment. The removal of NAs by pyrite/PS system was initially investigated. More than 90% of cyclohexanoic acid (CHA), a model NA, was removed in pyrite/PS system (2.0 g/L pyrite, 4.0 mM PS) at initial pH of 3-11. Scavenging experiments revealed that Fe(II) on pyrite surface was the reactive site for PS activation to generate reactive species, including sulfate radical (SO4·-), Fe(IV) and hydroxyl radical (·OH) for CHA degradation. Reactions of Fe(III) with S helped restore Fe(II) and enhance PS activation, resulting in the sustained catalytic activity of pyrites over five cycles. Cl-, SO42- and NO3- below 10 mM had minimal impact on CHA degradation in pyrite/PS system. However, over 1 mM of HCO3- inhibited 80% of CHA removal due to the buffer effect to maintain the high solution pH. Removing HCO3- from real PWW restored the removal of CHA and of total organic carbon (TOC) to over 90% and 71.3% in pyrite/PS system, respectively. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) results indicated that O2‒6 species including NAs were primarily eliminated through mineralization and oxygen addition. Besides, O3-5S, NO3-5S and N3O2‒4 species were the most susceptible to oxidation in PWW, resulting in the increase of the oxidation level (i.e., O/Cwa) from 0.41 to 0.56 after treatment. This study provides valuable insights into the treatment of NAs in real PWW, and potential application of natural minerals in the treatment of industrial wastewater.

BN-Butafulvenes and Their Application in the Synthesis of Highly Substituted BN-9,1-Naphthalenes.

BN-butafulvenes, mono-BN isosteres of butafulvene and highly strained isomers of azaborines and B-amino boroles, have been synthesized via hydrolysis of the urana-borabicyclic complexes obtained from the reactions of bis(alkynyl)boranes with an uranacyclopropene complex. Their 4-dimethylaminopyridine (DMAP) adducts can further isomerize to 1,2,4,6-multisubstituted BN-9,1-naphthalenes. Both NMR reaction monitoring and theoretical calculations point to a reaction mechanism involving dearomative insertion of DMAP followed by two consecutive 1,2-hydrogen shifts. The photophysical studies of the highly substituted BN-9,1-naphthalenes reveal a notable redshift in both the UV/Vis absorption and emission spectra. The (TD)-DFT calculations corroborate the experimental data, suggesting that the strong π-donating amino substitution at the 1- and/or 6-positions destabilizes the HOMO, and thus leading to a notable decrease of the HOMO-LUMO gap.

Phosphoric Acid-Catalyzed Enantioselective Synthesis of Axially Chiral Anthrone-based Compounds.

Anthrones and analogues are structural cores shared by diverse pharmacologically active natural and synthetic compounds. The sp2 -rich nature imposes inherent obstruction to introduce stereogenic element onto the tricyclic aromatic backbone. In our pursuit to expand the chemical space of axial chirality, a novel type of axially chiral anthrone-derived skeleton was discovered. This work establishes oxime ether as suitable functionality to furnish axial chirality on symmetric anthrone skeletons through stereoselective condensation of the carbonyl entity with long-range chirality control. The enantioenriched anthrones could be elaborated into dibenzo-fused seven-membered N-heterocycles containing well-defined stereogenic center via Beckmann rearrangement with axial-to-point chirality conversion.

Sublobar Resection Versus Lobectomy for Early-Stage Pulmonary Carcinoid Tumors ≤3 cm in Size: A SEER Population-Based Study.

OBJECTIVE: This study aimed to determine the optimal surgical procedure for early-stage pulmonary carcinoids (PCs). BACKGROUND: PCs, comprising typical carcinoids (TCs) and atypical carcinoids (ACs), are rare low-grade malignant tumors. We determine the optimal surgical management for early-stage PCs using data from the Surveillance, Epidemiology, and End Results registry. METHODS: Clinical and survival data of patients with early-stage PC tumors with a diameter ≤3 cm were retrieved. The Kaplan-Meier method and logrank tests were used to assess the differences in overall survival (OS). Subgroup analyses were also performed. To reduce the inherent bias of retrospective studies, two propensity score matching (PSM) analysis with (PSM2) or without (PSM1) consideration of lymph node assessment were performed. RESULTS: In total, 2934 patients with PCs, including 2741 (93.42%) with TCs and 193 (6.58%) with ACs, were recruited. After PSM1 analysis, TC patients in the lobectomy group had a significantly better OS than those in the sublobar resection group ( P = 0.0067), which is more remarkable for patients with a tumor diameter of 2 cm

Metabolic control of oocyte development†.

Well balanced and timed metabolism is essential for oocyte development. The effects of extrinsic nutrients on oocyte maturation have been widely reported. In contrast, intrinsic control of oogenesis by intracellular metabolites and metabolic enzymes has received little attention. The comprehensive characterization of metabolic patterns could lead to more complete understanding of regulatory mechanisms underlying oocyte development. A cell's metabolic state is integrated with epigenetic regulation. Epigenetic modifications in germ cells are therefore sensitive to parental environmental exposures. Nevertheless, direct genetic evidence for metabolites involvement in epigenetic establishment during oocyte development is still lacking. Moreover, metabolic disorder-induced epigenetic perturbations during oogenesis might mediate the inter/transgenerational effects of environmental insults. The molecular mechanisms responsible for this deserve further investigation. Here, we summarize the findings on metabolic regulation in oocyte maturation, and how it contributes to oocyte epigenetic modification. Finally, we propose a mouse model that metabolic disorder in oocyte serves as a potential factor mediating the maternal environment effects on offspring health.

Application of metagenomic next-generation sequencing for suspected infected pancreatic necrosis.

BACKGROUND: Metagenomic next-generation sequencing (mNGS) is increasingly used for the clinical diagnosis of infectious diseases, but there is a paucity of data regarding the application of mNGS in the early diagnosis of infected pancreatic necrosis (IPN). OBJECTIVE: To investigate the clinical application value of mNGS in the pathogenic diagnosis of IPN. METHODS: Forty-two patients with suspected IPN were prospectively and consecutively enrolled from August 2019 to August 2021. Blood samples were collected for mNGS and microbial culture simultaneously during fever (T ≥ 38.5 °C). For patients who had indications of surgical interventions, peri-pancreatic specimens were collected for mNGS and microbial culture simultaneously during the first surgical intervention to confirm IPN. The clinical performance of mNGS and microbial culture were compared. RESULTS: A total of 21 patients (50.0%) were confirmed to have IPN during hospitalization. The sensitivity of blood mNGS was significantly higher than blood culture (95.2% vs. 23.8%, P < 0.001) in diagnosing IPN. The negative predictive value of blood mNGS was 90.0%. The turnaround time of mNGS was significantly shorter than that of microbial culture [(37.70 ± 1.44) vs. (115.23 ± 8.79) h, P < 0.01] and the average costs of mNGS accounted for 1.7% of the average total cost of hospitalization. The survival analysis demonstrates that the positive blood mNGS result was not associated with increased mortality (P = 0.119). CONCLUSIONS: With more valuable diagnostic performance and shorter turnaround time, clinical mNGS represents a potential step forward in the early diagnosis of IPN.