Cloning and characterization of the histone variant gene H2A.Z in Bombyx mori.

H2A.Z, the most evolutionarily conserved variant of histone H2A, plays a pivotal role in chromatin remodeling and contributes significantly to gene transcription and genome stability. However, the role of H2A.Z in the silkworm (Bombyx mori) remains unclear. In this study, we cloned the BmH2A.Z from B. mori. The open reading frame of BmH2A.Z is 390 bp, encoding 129 amino acids, with a confirmed molecular weight of 13.4 kDa through prokaryotic expression analysis. Sequence analysis revealed that BmH2A.Z has a conserved H2A.Z domain and is closely related to the systemic evolution of other known H2A.Zs. The expression profile of BmH2A.Z at various developmental stages of the B. mori exhibited the highest expression level in the 1st instar, followed by the grain stage and the 2nd instar, and the lowest expression level in the moth. The highest transcript level of BmH2A.Z was observed in the head, with relatively lower levels detected in the blood than in the other tissues under consideration. In addition, the upregulation of BmH2A.Z resulted in the amplified expression of B. mori nucleopolyhedrovirus (BmNPV) genes, thus facilitating the proliferation of BmNPV. This study establishes a foundation for investigating the role of BmH2A.Z in B. mori and its participation in virus-host interactions.

Combined traditional Chinese medicine therapy for the treatment of infertility with polycystic ovary syndrome: A network meta-analysis of randomized controlled trials.

BACKGROUND: Polycystic ovary syndrome (PCOS) infertility has attracted great attention from researchers due to its high incidence. Numerous studies have shown that Chinese medicine is effective in treating this disease, but there is a wide variety of Chinese medicine therapies available, and there is a lack of comparative evaluation of the efficacy of various Chinese medicine combination therapies in the clinic, which requires further in-depth exploration. This study aims to evaluate the efficacy of a combined traditional Chinese medicine (TCM) therapy for the treatment of infertility with PCOS using network meta-analysis (NMA). METHODS: In PubMed, web of Science, Cochrane Library, Embase, China Knowledge Network, Wanfang Data, VIP Database, China Biomedical Literature Database (SinoMed) databases, searchs were conducted for information about the randomized controlled trials (RCTs) of combined TCM therapy for the treatment of infertility with PCOS. Quality evaluation was performed using the Cochrane 5.3 risk of bias assessment tool, and NMA using Stata 16.0. RESULTS: This study comprised 28 RCTs using 8 combined TCM therapies in total. The results of the NMA showed that moxibustion + herbal, fire acupuncture + herbal, acupuncture + herbal, electroacupuncture + herbal, and acupoint application + herbal improved the clinical pregnancy rate better than acupuncture, herbal, and western medicines monotherapy (P < .05). Additionally, ear point pressure + herbal enema + herbal, acupuncture and moxibustion + herbal, fire acupuncture + herbal, and acupuncture + herbal improved the ovulation rate better than acupuncture, herbal, and western medicines monotherapy (P < .05). Moxibustion + herbal, fire acupuncture + herbal, and acupuncture + herbal are the 3 most effective therapies for improving the clinical pregnancy rate. Fire acupuncture + herbal, acupuncture + herbal, and ear point pressure + herbal enema + herbal are the 3 most effective therapies for improving the ovulation rate. CONCLUSION: The combined TCM therapy demonstrated better efficacy for the treatment of infertility with PCOS compared to acupuncture, herbal, and western medicines monotherapy. However, the optimal treatment therapy varied depending on the outcome indicators. Further large sample, high-quality, and standardized RCTs are needed to verify these findings.

The efficacy and safety of Bazi Bushen Capsule in treating premature aging: A randomized, double blind, multicenter, placebo-controlled clinical trial.

PURPOSE: It is unclear whether traditional Chinese patent medicines can resist premature aging. This prospective study investigated the effects of Bazi Bushen Capsule (BZBS) which is a traditional Chinese patent medicine for tonifying the kidney essence on premature senility symptoms and quality of life, telomerase activity and telomere length. STUDY DESIGN AND METHODS: It was a parallel, multicenter, double-blind, randomized, and placebo-controlled trial. Subjects (n = 530) aged 30-78 years were randomized to receive BZBS or placebo capsules 12 weeks. The primary outcome was the clinical feature of change in kidney deficiency for aging evaluation scale (CFCKD-AES) and tilburg frailty indicator (TFI). The secondary outcomes were SF-36, serum sex hormone level, five times sit-to-stand time (FTSST), 6MWT, motor function test-grip strength, balance test, walking speed, muscle mass measurement, telomerase and telomere length. RESULTS: After 12 weeks of treatment, the CFCKD-AES and TFI scores in the BZBS group decreased by 13.79 and 1.50 respectively (6.42 and 0.58 in the placebo group, respectively); The SF-36 in the BZBS group increased by 98.38 (23.79 in the placebo group). The FTSST, motor function test grip strength, balance test, walking speed, and muscle mass in the elderly subgroup were all improved in the BZBS group. The telomerase content in the BZBS group increased by 150.04 ng/ml compared to the placebo group. The fever led one patient in the placebo group to discontinue the trial. One patient in the placebo group withdrew from the trial due to pregnancy. None of the serious AEs led to treatment discontinuation, and 3 AEs (1.14%) were assessed as related to BZBS by the primary investigator. CONCLUSIONS: BZBS can improve premature aging symptoms, frailty scores, and quality of life, as well as improve FTSST, motor function: grip strength, balance test, walking speed, and muscle mass in elderly subgroups of patients, and enhance telomerase activity, but it is not significantly associated with increasing telomere length which is important for healthy aging. TRIAL REGISTRY: https://www.chictr.org.cn/showproj.html?proj=166181.

[Characteristics of soil moisture limitation and non-limitation in the response of sap flow to transpiration driving factors]. / æ ‘å¹²æ¶²æµå¯¹è’¸è ¾é©±åŠ¨å› å­å“åº”çš„åœŸå£¤æ°´åˆ†é™åˆ¶ä¸Žéžé™åˆ¶ç‰¹å¾.

Transpiration is a significant part of water cycle in forest ecosystems, influenced by meteorological factors and potentially constrained by soil moisture. We used Granier-type thermal dissipation probes to monitor xylem sap flow dynamics of three tree species (Quercus liaotungensis, Platycladus orientalis, and Robinia pseudoacacia) in a semi-arid loess hilly region, and to continuously monitor the key meteorological factors and soil water content (SWC). We established the SWC thresholds delineating soil moisture-limited and -unlimited sap flow responses to transpiration drivers. The results showed that mean sap flux density (Js) of Q. liaotungensis and R. pseudoacacia was significantly higher during period with higher soil moisture compared to lower soil moisture, while the difference in Js for P. orientalis between the two periods was not significant. We used an exponential saturation function to fit the relationship between the Js of each tree species and the integrated transpiration variable (VT) which reflected solar radiation and vapor pressure deficit. The difference in the fitting curve parameters indicated that there were distinct response patterns between Js and VT under different soil moisture conditions. There was a threshold in soil moisture limitation on sap flow for each species, which was identified as 0.129 m3·m-3 for Q. liaotungensis, 0.116 m3·m-3 for P. orientalis, and 0.108 m3·m-3 for R. pseudoacacia. Below the thresholds, Js was limited by soil moisture. Above these points, the normalized sensitivity index (NSI) for Q. liaotungensis and P. orientalis reached saturation, while that of R. pseudoacacia did not reach saturation but exhibited a significant reduction in moisture limitation. Among the three species, P. orientalis was the most capable of overcoming soil moisture constraints.

Effects of multi-frequency ultrasound-assisted immersion freezing processing on myofibrillar protein structure and lipid oxidation of large yellow croaker (Larimichthys crocea) during long-time frozen storage.

In this study, large yellow croaker (Larimichthys crocea) was frozen using multi-frequency ultrasound-assisted freezing (MUIF) with different powers (160 W, 175 W, and 190 W, respectively) and stored at -18 °C for ten months. The effect of different ultrasound powers on the myofibrillar protein (MP) structures and lipid oxidation of large yellow croaker was investigated. The results showed that MUIF significantly slowed down the oxidation of MP by inhibiting carbonyl formation and maintaining high sulfhydryl contents. These treatments also held a high activity of Ca2+-ATPase in the MP. MUIF maintained a higher ratio of α-helix to ß-sheet during frozen storage, thereby protecting the secondary structure of the tissue and stabilizing the tertiary structure. In addition, MUIF inhibited the production of thiobarbituric acid reactive substances value and the loss of unsaturated fatty acid content, indicating that MUIF could better inhibit lipid oxidation of large yellow croaker during long-time frozen storage.

High-performance self-cascade nanoreactors for combined ferroptosis, photothermal therapy, and starving therapy.

Despite the great potential of starving therapy caused by nanoreactor based on glucose oxidase (GOX) in tumor therapy, efficiency and uncontrolled reaction rates in vivo lead to inevitable toxicity to normal tissues, which seriously hindering their clinical conversion. Herein, a cascade nanoreactor (GOX/Mn/MPDA) was constructed by coating mesoporous polydopamine nanoparticles (MPDA) with MnO2 shell and then depositing GOX into honeycomb-shaped manganese oxide nanostructures to achieve a combination of ferroptosis, photothermal therapy and starving therapy. Upon uptake of nanodrugs to cancer cells, the MnO2 shell would deplete glutathione (GSH) and produce Mn2+, while a large amount of H2O2 generated from the catalytic oxidation of glucose by GOX would accelerate the Fenton-like reaction mediated by Mn2+, producing high toxic •OH. More importantly, the cascade reaction between GOX and MnO2 would be further strengthened by localized hyperthermia caused by irradiated by near-infrared laser (NIR), inducing significant anti-tumor effects in vitro and in vivo. Regarding the effectiveness of tumor treatment in vivo, the tumor inhibition rate achieved an impressive 64.33%. This study provided a new strategy for anti-tumor therapeutic by designing a photothermal-enhanced cascade catalytic nanoreactor.

Mitochondria- and endoplasmic reticulum-localizing iridium(III) complexes induce immunogenic cell death of 143B cells.

Recent breakthroughs in cancer immunology have propelled immunotherapy to the forefront of cancer research as a promising treatment approach that harnesses the body's immune system to effectively identify and eliminate cancer cells. In this study, three novel cyclometalated Ir(III) complexes, Ir1, Ir2, and Ir3, were designed, synthesized, and assessed in vitro for cytotoxic activity against several tumor-derived cell lines. Among these, Ir1 exhibited the highest cytotoxic activity, with an IC50 value of 0.4 ± 0.1 µM showcasing its significant anticancer potential. Detailed mechanistic analysis revealed that co-incubation of Ir1 with 143B cells led to Ir1 accumulation within mitochondria and the endoplasmic reticulum (ER). Furthermore, Ir1 induced G0/G1 phase cell cycle arrest, while also diminishing mitochondrial membrane potential, disrupting mitochondrial function, and triggering ER stress. Intriguingly, in mice the Ir1-induced ER stress response disrupted calcium homeostasis to thereby trigger immunogenic cell death (ICD), which subsequently activated the host antitumor immune response while concurrently dampening the in vivo tumor-induced inflammatory response.

Dahuang Zhechong Pill Alleviates Liver Fibrosis Progression by Regulating p38 MAPK/NF-κ B/TGF-ß1 Pathway.

OBJECTIVE: To explore the effect and mechanism of Dahuang Zhechong Pill (DHZCP) on liver fibrosis. METHODS: Liver fibrosis cell model was induced by transforming growth factor-ß (TGF-ß) in hepatic stellate cells (HSC-T6). DHZCP medicated serum (DMS) was prepared in rats. HSC-T6 cells were divided into the control (15% normal blank serum culture), TGF-ß (15% normal blank serum + 5 ng/mL TGF-ß), DHZCP (15% DMS + 5 ng/mL TGF-ß), DHZCP+PDTC [15% DMS + 4 mmol/L ammonium pyrrolidine dithiocarbamate (PDTC)+ 5 ng/mL TGF-ß], and PDTC groups (4 mmol/L PDTC + 5 ng/mL TGF-ß). Cell activity was detected by cell counting kit 8 and levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the cell supernatant were determined by enzyme-linked immunosorbnent assay. Western blot was used to measure the expressions of p38 mitogen-activated protein kinase/nuclear factor kappa B/transforming growth factor-ß1 (p38 MAPK/NF-κ B/TGF-ß1) pathway related proteins, and the localization and expressions of these proteins were observed by immunofluorescence staining. RESULTS: DHZCP improves the viability of cells damaged by TGF-ß and reduces inflammatory cytokines and ALT and AST levels in the supernatant of HSC-T6 cells induced with TGF-ß (P<0.05 or P<0.01). Compared with the TGF-ß group, NF-κ B p65 levels in the DHZCP group were decreased (P<0.05). p38 MAPK and NF-κ B p65 levels in the DHZCP+PDTC were also reduced (P<0.01). Compared with the TGF-ß group, the protein expression of Smad2 showed a downward trend in the DHZCP, DHZCP+PDTC, and PDTC groups (all P<0.01), and the decreasing trend of Samd3 was statistically significant only in DHZCP+PDTC group (P<0.01), whereas Smad7 was increased (P<0.05 or P<0.01). CONCLUSION: DHZCP can inhibit the process of HSC-T6 cell fibrosis by down-regulating the expression of p38 MAPK/NF-κ B/TGF-ß1 pathway.

[A new cucurbitane glycoside from Picrorhiza scrophulariiflora].

Chemical constituents from the ethanol extract of Picrorhiza scrophulariiflora were isolated and purified by column chromatography. Their structures were identified by HR-MS, 1D and 2D-NMR, and their cytotoxicity was assessed by CCK-8 assay. Four compounds were isolated and identified as follows: 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosterol-5,25-diene-22-one(1), 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,24-diene-22-one(2), 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5-ene-22-one(3) and 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,23-(E)-diene-22-one(4). Compound 1 represents a new cucurbitane glycoside. The half inhibitory concentrations of the 4 compounds exceeded 100 µmol·L~(-1) against four tumor cell lines, indicating no significant cytotoxicity.

Effects of eugenol on physicochemical properties of sturgeon skin collagen-chitosan composite membrane.

In this study, a series of collagen-chitosan-eugenol (CO-CS-Eu) flow-casting composite films were prepared using collagen from sturgeon skin, chitosan, and eugenol. The physicochemical properties, mechanical properties, microstructure, as well as antioxidant and antimicrobial activities of the composite membranes were investigated by various characterization techniques. The findings revealed that the inclusion of eugenol augmented the thickness of the film, darkened its color, reduced the transparency, and enhanced the ultraviolet light-blocking capabilities, with the physicochemical properties of the CO-CS-0.25%Eu film being notably favorable. Eugenol generates increasingly intricate matrices that disperse within the system, thereby modifying the optical properties of the material. Furthermore, the tensile strength of the film decreased from 70.97 to 20.32 MPa, indicating that eugenol enhances the fluidity and ductility of the film. Added eugenol also exhibited structural impact by loosening the film cross-section and decreasing its density. The Fourier transform infrared spectroscopy results revealed the occurrence of several intermolecular interactions among collagen, chitosan, and eugenol. Moreover, the incorporation of eugenol bolstered the antioxidant and antimicrobial capabilities of the composite film. This is primarily attributed to the abundant phenolic/hydroxyl groups present in eugenol, which can react with free radicals by forming phenoxy groups and neutralizing hydroxyl groups. Consequently, inclusion of eugenol substantially enhances the freshness retention performance of the composite film. PRACTICAL APPLICATION: ● The CO-CS-Eu film utilizes collagen from sturgeon skin, improving the use of sturgeon resources.● Different concentrations of eugenol altered its synergistic effect with chitosan.● The CO-CS-Eu film is composed of natural products with safe and edible properties.

M6[Cd2(CO3)2(B12O18)(OH)6] (M = K, Rb): Borate-Carbonates with Two CdCO3 Embedded in a Cyclic Oxoboron Anion.

Two metal borate-carbonates, M6[Cd2(CO3)2(B12O18)(OH)6] [M = K (1), Rb (2)], were obtained under surfactant-thermal conditions. In 1 and 2, each cyclic [(B12O18)(OH)6]6- anion captures two CdCO3 in two sides of the rings and finally forms the unusual (CdCO3)2@[(B12O18)(OH)6] cluster. Both 1 and 2 show moderate birefringence. Density functional theory calculations indicate that carbonate groups have a major contribution to electron-related optical transition.

Comprehensive strategies for controlling Listeria monocytogenes biofilms on food-contact surfaces.

Listeria monocytogenes biofilms formed on food-contact surfaces within food-processing facilities pose a significant challenge, serving as persistent sources of cross-contamination. In this review, we examined documented cases of foodborne outbreaks and recalls linked to L. monocytogenes contamination on equipment surfaces and in the food production environment, provided an overview of the prevalence and persistence of L. monocytogenes in different food-processing facilities, and discussed environmental factors influencing its biofilm formation. We further delved into antimicrobial interventions, such as chemical sanitizers, thermal treatments, biological control, physical treatment, and other approaches for controlling L. monocytogenes biofilms on food-contact surfaces. This review provides valuable insights into the persistent challenge of L. monocytogenes biofilms in food processing, offering a foundation for future research and practical strategies to enhance food safety.

In Situ Characterizations of the Dynamics of Cathode Electrolyte Interfaces at Different Current Densities.

LiNi0.8Mn0.1Co0.1O2 with high nickel content plays a critical role in enabling lithium metal batteries (LMBs) to achieve high specific energy density, making them a prominent choice for electric vehicles (EVs). However, ensuring the long-term cycling stability of the cathode electrolyte interfaces (CEIs), particularly at fast-charge conditions, remains an unsolved challenge. The decay mechanism associated with CEIs and electrolytes in LMB at high current densities is still not fully understood. To address this issue, in situ Fourier transform infrared (FTIR) is employed to observe the dynamic process of formation/disappearance/regeneration of CEIs during charge and discharge cycles. These dynamic processes further exacerbate the instability of CEIs as current density increases, leading to rupture and dissolution of CEIs and subsequent deterioration in battery performance because of continuous electrolyte reactions. Additionally, the dynamic changes occurring within individual components of CEIs at different cycling stages and various current densities are also discussed. The results demonstrate that excellent capacity retention at small current density is attributed to enrichment of inorganic compounds (Li2CO3, LiF, etc.) and rendering better stability and smaller expansion of CEIs. The key to achieving excellent electrochemical performance at high current densities lies on protecting CEIs, mainly inorganic components.

16S rRNA sequencing in chronic dacryocystitis.

CLINICAL RELEVANCE: The pathogenesis of chronic dacryocystitis (CDC) is associated with a variety of bacteria. Investigating microflora has the potential to provide a theoretical basis for preventing and treating CDC. BACKGROUND: 16S rRNA sequencing is a sequence-based bacterial analysis. The application of 16S rRNA sequencing in CDC is rarely reported. METHODS: A case-control study of infected and healthy eyes diagnosed as CDC patients was conducted. Seventy-eight patients were divided into A (conjunctival sac secretions from healthy eyes), B (conjunctival sac secretions from affected eyes), and C (lacrimal sac secretions from affected eyes) groups. The flora of samples was analysed with 16S rRNA sequencing, and the data was analysed using QIIME, R, LefSE and other software. The potential functions were analysed by PICRUSt. RESULTS: A total of 1440 operational taxonomic units (OTUs) were obtained, 139 specific to group A, 220 specific to group B, and 239 specific to group C. There was no significant difference in α index between the three groups. The beta diversity and grouping analysis data indicated that the three groups of flora were similar in species richness and diversity, but there were some differences in composition. In group A, the abundance of Pseudomonadaceae, Chlorobacteria, Moraceae, Staphylococcaceae, Bacillariophyceae, Immunobacterium spp. and Bacillus spp. was higher; in group B, the abundance of Burkholderiaceae, Sphingomonas, Rhizobia, Stalked Bacteria, Sphingomonadaceae, Enterobacteriaceae, Shortwaveomonas spp. was higher; in group C, the abundance of Streptococcus digestiveis, Propionibacterium, Enterobacteriaceae, Anaerobacteriaceae, Propionibacteriaceae, Bacillus spp. Neisseria spp. and Shortactomonas spp. was higher. Six pathways were identified to assess the potential microbial functions. CONCLUSION: Alterations in the microbiota of the conjunctiva and lacrimal sac are associated with the pathogenesis of CDC, which may provide certain guidance for antibiotic treatment of CDC.

Failure mechanisms of the Li(Ni0.6Co0.2Mn0.2)O2-Li4Ti5O12 lithium-ion batteries in long-time high-rate cycle.

With the ever-growing widespread use of lithium-ion batteries in heavy machinery and daily life, the demand for improved longevity and high-rate performance is escalating. While Li4Ti5O12 (LTO) batteries excel in safety and cycling performance, their full potential for long-term, high-rate cycling still yet remains unrealized. In this paper, we present an analysis of a pouch battery with an LTO anode system that was cycled for an extended period at high rates. We compared the performance changes and internal component properties between fresh and cycled batteries. Our results reveal that, after tens of thousands of high-rate cycles, microcracks emerged on the cathode electrode material (NCM622) particles of the battery, whereas the LTO remained largely unchanged. Additionally, we observed significant electrolyte reduction, characterized the separator surface, and measured its properties. Our findings indicate that the electrolyte reactions are the primary cause of battery failure, leading to capacity fading and impedance increase. This research provides valuable insights into the failure mechanisms of lithium-ion batteries at high rates, thus contributing to the improvement of high-rate lithium-ion batteries.

Comparison of psoas major activation during standing hip flexion between chronic low back pain and healthy populations.

BACKGROUND: The psoas major (PM) has been identified as a potential contributor to chronic low back pain (LBP). However, few studies have investigated the effects of upright functional movement on PM activation in cLBP individuals. OBJECTIVE: This cross-sectional study aims to compare PM muscle activation characteristics in chronic LBP (cLBP) and healthy subjects during the transition from quiet double-leg standing to standing hip flexion. METHODS: Ultrasound Imaging was used to assess PM thickness at the lumbar vertebral level of L4-5 in 12 healthy and 12 cLBP participants. The changes in thickness between the test positions were utilized as a proxy for PM activation. RESULTS: The cLBP group exhibited greater thickness changes on the non-dominant side PM during contralateral hip flexion but not ipsilateral hip flexion (p= 0.369) compared to their healthy counterparts (p= 0.011; cLBP: resting 27.85 mm, activated 34.63 mm; healthy: resting 29.51 mm, activated 29.00 mm). There were no significant differences in dominant side PM thickness changes between the two groups during either contralateral or ipsilateral hip flexion (p= 0.306 and p= 0.077). CONCLUSION: Our findings suggest a potential overactivation of the PM in the cLBP population. This insight may aid in the development of tailored rehabilitation programs.

Effect of tea polyphenol-trehalose complex coating solutions on physiological stress and flesh quality of marine-cultured Turbot Scophthalmus maximus during waterless transport.

OBJECTIVE: The waterless transport of live fish has changed the present situation of live-fish transport. However, the waterless transport environment may cause stress in fish. This research evaluated the effect of tea polyphenol-trehalose (TPT) coating solutions on Turbot Scophthalmus maximus during waterless transport. METHODS: After cold acclimation, Turbot were coated and subsequently transported in a waterless environment for 18 h. Physiological and biochemical parameters were measured, including lysozyme (LZM) and immunoglobulin M (IgM) activities, serum creatinine (Cr) and uric acid (UA) concentrations, and nutritional flavor. RESULT: The results showed that the nonspecific immunity of Turbot was inhibited during the waterless transport; the LZM activity first increased and then decreased, and the serum Cr and UA concentrations significantly increased. In addition, the waterless transport promoted the breakdown of Turbot flesh proteins, leading to changes in nucleotides and free amino acids (FAAs). After waterless transport, the LZM and IgM activities in the TPT-treated Turbot were higher than those in the control group (CK), and the changes in FAA content and nucleotides were smaller than those observed in the CK group. CONCLUSION: This study shows that the use of TPT coating solution can reduce the impact of waterless transportation stress on the immune and metabolic functions of Turbot and can maintain the meat quality and flavor of Turbot.

α-Ketoglutarate for Preventing and Managing Intestinal Epithelial Dysfunction.

The epithelium lining the intestinal tract serves a multifaceted role. It plays a crucial role in nutrient absorption and immune regulation and also acts as a protective barrier, separating underlying tissues from the gut lumen content. Disruptions in the delicate balance of the gut epithelium trigger inflammatory responses, aggravate conditions such as inflammatory bowel disease, and potentially lead to more severe complications such as colorectal cancer. Maintaining intestinal epithelial homeostasis is vital for overall health, and there is growing interest in identifying nutraceuticals that can strengthen the intestinal epithelium. α-Ketoglutarate, a metabolite of the tricarboxylic acid cycle, displays a variety of bioactive effects, including functioning as an antioxidant, a necessary cofactor for epigenetic modification, and exerting anti-inflammatory effects. This article presents a comprehensive overview of studies investigating the potential of α-ketoglutarate supplementation in preventing dysfunction of the intestinal epithelium.

AMPK Suppression Due to Obesity Drives Oocyte mtDNA Heteroplasmy via ATF5-POLG Axis.

Due to the exclusive maternal transmission, oocyte mitochondrial dysfunction reduces fertility rates, affects embryonic development, and programs offspring to metabolic diseases. However, mitochondrial DNA (mtDNA) are vulnerable to mutations during oocyte maturation, leading to mitochondrial nucleotide variations (mtSNVs) within a single oocyte, referring to mtDNA heteroplasmy. Obesity (OB) accounts for more than 40% of women at the reproductive age in the USA, but little is known about impacts of OB on mtSNVs in mature oocytes. It is found that OB reduces mtDNA content and increases mtSNVs in mature oocytes, which impairs mitochondrial energetic functions and oocyte quality. In mature oocytes, OB suppresses AMPK activity, aligned with an increased binding affinity of the ATF5-POLG protein complex to mutated mtDNA D-loop and protein-coding regions. Similarly, AMPK knockout increases the binding affinity of ATF5-POLG proteins to mutated mtDNA, leading to the replication of heteroplasmic mtDNA and impairing oocyte quality. Consistently, AMPK activation blocks the detrimental impacts of OB by preventing ATF5-POLG protein recruitment, improving oocyte maturation and mitochondrial energetics. Overall, the data uncover key features of AMPK activation in suppressing mtSNVs, and improving mitochondrial biogenesis and oocyte maturation in obese females.

Promoting hEalthy Diet and Active Lifestyle (PEDAL): a protocol for the development and feasibility study of a multicomponent intervention among primary school children in Singapore.

BACKGROUND: Setting healthy lifestyle habits during the formative years of childhood is critical as habits can track to adulthood and help prevent obesity and chronic disease risks in later life. While multicomponent interventions have been shown to be effective in changing the lifestyle behaviours of children, there is a limited understanding of the feasibility of such interventions in primary schools in Singapore. A multiphase mixed method study was conducted to develop and examine the feasibility of a theory-based multicomponent school-based intervention-Promoting hEatlthy Eating and Active Lifestyle (PEDAL). METHODS: Underpinned by Kincaid's ideation model, the PEDAL intervention was developed to increase fruit and vegetable consumption and decrease sedentary behaviours among children. This study consists of three phases. Phase 1 details the development of PEDAL, which consists of four components: (A) a series of interactive health education lessons, (B) actionable home activities to support habit formation, (C) parental/guardian engagement, and (D) optimising the school environment. In Phase 2, components A and B of PEDAL were implemented in two public, co-educational primary schools among Primary 5 students (aged 10-12 years) in Singapore. Data was collected quantitatively using questionnaires and qualitatively using focus group discussions (FGDs) with students and teachers. The feasibility dimensions of components A and B, including recruitment capability, data collection, social validity, and practicality were examined, and ideation on healthy eating and physical activity was explored. In Phase 3, the full PEDAL intervention was pilot-tested in two other public, co-education primary schools with the same target population, using a concurrent mixed method quasi-experimental study design. Feasibility dimensions and potential effectiveness of the intervention will be assessed. DISCUSSION: This study will provide insights into the feasibility of PEDAL and inform its refinement. Findings from the pilot test will guide the planning of a larger-scale definitive trial. TRIAL REGISTRATION: Registered with ISRCTN registry (ISRCTN16114046) on 16 October 2022.