lncSNHG16 promotes hepatocellular carcinoma development by inhibiting autophagy.

OBJECTIVE: To investigate the expression of long non-coding RNA lncSNHG16 in hepatocellular carcinoma (HCC), associations between its expression and patient survival, and its potential role in regulating autophagy in the disease. METHODS: Expression of lncSNHG16 was measured using quantitative real-time PCR in HCC cells in culture and HCC tissues from patients. Effects of lncSNHG16 overexpression were examined in HCC cultures using assays of cell proliferation, wound healing, and migration or invasion in Transwell dishes. Effects of lncSNHG16 overexpression were also examined in subcutaneous tumor in mice. Relationships of lncSNHG16 expression to autophagy and apoptosis in HCC cultures were explored using western blotting and flow cytometry. RESULTS: Higher lncSNHG16 expression in HCC tissues was associated with significantly worse overall and recurrence-free survival of patients. Overexpressing lncSNHG16 in HCC cell culture promoted cell proliferation, migration, and invasion while suppressing apoptosis. lncSNHG16 was associated with upregulation of STAT3 as well as inhibition of autophagy and associated apoptosis. Overexpressing lncSNHG16 accelerated tumor growth and weight in mice. CONCLUSION: The non-coding RNA lncSNHG16 suppresses autophagy and associated apoptosis in HCC, making it a potential therapeutic target.

Encouraging Breastfeeding Without Guilt: A Qualitative Study of Breastfeeding Promotion in the Singapore Healthcare Setting.

Introduction: In Singapore, the healthcare system strongly encourages mothers to breastfeed and breastfeeding initiation is near-universal. However, sustained breastfeeding rates remain low. Little is currently known about how breastfeeding information disseminated in the healthcare setting influences women's breastfeeding experiences. This study explored breastfeeding promotion and educational resources from the perspective of Singaporean mothers and healthcare workers. Methods: Semi-structured interviews with 14 mothers of infants aged 1-5 months and who had used obstetric, maternity, and/or paediatric services in Singapore, and 20 health workers with experience in general, obstetric, maternal, or paediatric care recruited using purposive sampling methods. Interview transcripts were coded using an inductive method. Results: Breastfeeding communications were viewed as too moralized and too focused on nudging women to breastfeed, with relatively little emphasis on timely, practical information or solutions for mothers unable to latch. Hence mothers tended to rely on alternative resources such as blogs. They lacked in-depth knowledge of the benefits of breastfeeding and viewed it as detrimental to maternal mental wellbeing due to the perceived stress and guilt when experiencing difficulties, notably with milk supply and latching, and from the inability to meet breastfeeding expectations. Husbands, older family members, confinement nannies, and employers were considered influential individuals to encourage breastfeeding, but they commonly discouraged breastfeeding due to social and cultural factors which led to supplementation with formula. Conclusion: For better breastfeeding outcomes, future informational sources on breastfeeding should be morally neutral, practical, set realistic expectations for the demands of breastfeeding, and target influential individuals such as family members, confinement nannies and employers.

Targeting cell death in NAFLD: mechanisms and targeted therapies.

Nonalcoholic fatty liver disease (NAFLD) is a group of chronic liver disease which ranges from simple steatosis (NAFL) to non-alcoholic steatohepatitis (NASH) and is characterized by lipid accumulation, inflammation activation, fibrosis, and cell death. To date, a number of preclinical studies or clinical trials associated with therapies targeting fatty acid metabolism, inflammatory factors and liver fibrosis are performed to develop effective drugs for NAFLD/NASH. However, few therapies are cell death signaling-targeted even though the various cell death modes are present throughout the progression of NAFLD/NASH. Here we summarize the four types of cell death including apoptosis, necroptosis, pyroptosis, and ferroptosis in the NAFLD and the underlying molecular mechanisms by which the pathogenic factors such as free fatty acid and LPS induce cell death in the pathogenesis of NAFLD. In addition, we also review the effects of cell death-targeted therapies on NAFLD. In summary, our review provides comprehensive insight into the roles of various cell death modes in the progression of NAFLD, which we hope will open new avenues for therapeutic intervention.

Exploring Brominated Aromatic Butenolides from Aspergillus terreus EGF7-0-1 with Their Antifungal Activities.

Fungal diseases could severely harm agricultural productions. To develop new antifungal agents, based on the Global Natural Products Social Molecular Networking, typical bromine isotope peak ratios, and ultraviolet absorptions, cultivation of the soft coral-derived endophytic fungi Aspergillus terreus EGF7-0-1 with NaBr led to the targeted isolation of 14 new brominated aromatic butenolides (1-14) and six known analogues (15-20). Their structures were elucidated by extensive spectroscopic analysis and quantum chemical calculations. Compounds 1-14 exhibited wildly antifungal activities (against Colletotrichum gloeosporioides, Pestalotiopsis microspora, Fusarium oxysporum f. sp. cubense, Botrytis cinerea, and Diaporthe phoenicicola). The bioassay results showed that compounds 1-14 exhibited excellent antifungal activities against C. gloeosporioides, with concentration for 50% of maximal effect (EC50) values from 2.72 to 130.41 nM. The mechanistic study suggests that compound 1 may disrupt nutrient signaling pathways by reducing the levels of metabolites, such as carbohydrates, lipids, and amino acids, leading to an increase in low-density granules and a decrease in high-density granules in the cytoplasm, accompanied by numerous vacuoles, thereby inhibiting the growth of C. gloeosporioides. Monobrominated γ-butenolide 1 may be expected to exploit a novel agriculturally antifungal leading drug. Meanwhile, compound M1 has conformed antifugual activities against C. gloeosporioides by papayas in vivo.

Identification of a pathogenic variant and pre-implantation genetic testing for a Chinese family affected with split-hand/foot malformation.

Split-hand/foot malformation is a serious congenital limb malformation characterized by syndactyly and underdevelopment of the phalanges and metatarsals. In this study, we reported a case of a fetus with hand-foot cleft deformity. Whole exome and Sanger sequencing were used to filter out candidate gene mutation sites and provide pre-implantation genetic testing(PGT) for family members. Genetic testing results showed that there was a homozygous mutation c.786G>A (p.Trp262*) in the fetal WNT10B, and both parents were carriers of heterozygous mutations. PGT results showed that out of the two blastocysts, one was a heterozygous mutant and the other was a homozygous mutant. All the embryos had diploid chromosomes. The heterozygous embryo was transferred, and a singleton pregnancy was successfully achieved. This study suggests that homozygous mutations in WNT10B are the likely cause of hand-foot clefts in this family. For families with monogenic diseases, preimplantation genetic testing can effectively prevent the birth of an affected child only after identifying the pathogenic mutation.

Impact of High Sodium Diet on Neovascularization and Osseointegration around Titanium Implant: An in Vivo and in Vitro Study.

Objective: A high sodium (HS) diet is believed to affect bone metabolism processes. Clarifying its impact on osseointegration of titanium (Ti) implants holds significant implications for postoperative dietary management of implanted patients. Methods: This investigation probed the impact of sodium ions (Na +) on neovascularization and osteogenesis around Ti implants in vivo, utilizing micro-computed tomography, hematoxylin and eosin staining, and immunohistochemical analyses. Concurrently, in vitro experiments assessed the effects of varied Na + concentrations and exposure durations on human umbilical vein endothelial cells (HUVECs) and MC3T3-E1 cells. Results: In vivo, increased dietary sodium (0.8%-6.0%) led to a substantial decline in CD34 positive HUVECs and new bone formation around Ti implants, alongside an increase in inflammatory cells. In vitro, an increase in Na + concentration (140-150 mmol/L) adversely affected the proliferation, angiogenesis, and migration of HUVECs, especially with prolonged exposure. While MC3T3-E1 cells initially exhibited less susceptibility to high Na + concentrations compared to HUVECs during short-term exposure, prolonged exposure to a HS environment progressively diminished their proliferation, differentiation, and osteogenic capabilities. Conclusion: These findings suggest that HS diet had a negative effect on the early osseointegration of Ti implants by interfering with the process of postoperative vascularized bone regeneration.

Alginate oligosaccharides exert protective effects on hydrogen peroxide-induced senescence in H9C2 cardiomyocytes by regulating the redox state of cells.

Aging is a known independent risk factor for several cardiovascular diseases. Here, we evaluated potential effects and possible mechanisms through which alginate oligosaccharides (AOS) affect hydrogen peroxide (H2O2)-induced senescence in H9C2 cardiomyocytes. A series of AOS molecules, including oligoM, oligoG, M-5, and G-5, were investigated. AOS significantly decreased SA-ß-gal and DAPI-stained positive cells, downregulated p53 and p21 (aging-related markers) expression, and eventually protected H9C2 cells from H2O2-induced senescence. AOS decreased reactive oxygen species and malondialdehyde production, recovered mitochondrial function, and alleviated the oxidative stress state by regulating PGC-1α and NADPH oxidase subunit expression. Furthermore, AOS treatment restored the expression of antioxidant enzymes in senescent H9C2 cells. Thus, our results show in vitro evidence that AOS alleviate senescence in H9C2 cells by regulating the redox state; thus, AOS may be an effective therapeutic agent that could protect against cardiomyocyte senescence.

S-Arylation of Thioic S-Acid Using Thianthrenium Salts via Photoactivation of Electron Donor-Acceptor Complex.

Thioesters make up an important class of bioactive compounds. Due to their chemoselectivity, they have been widely used in the synthesis of a wide range of complex bioactive molecules and natural products. At present, chemists have developed a variety of methods for the preparation of thioester compounds. However, these methods usually require the use of transition metal catalysis or harsh reaction conditions. The strategy of synthesizing thioester compounds via visible light-induced electron donor-acceptor (EDA) complex reactions avoids the problems associated with conventional methods through the development of photocatalysis. Here we report a sustainable method for thiocarbonylating aryl sulfonium salts via a visible light-induced EDA complex process without transition metals.

Enhancing Short-Range Interactions to Broaden the Temperature Range for Coexistence of Antiferroelectricity and Ferroelasticity.

Antiferroelectric (AFE) materials, characterized by double electric hysteresis loops, can be transformed to the ferroelectric (FE) phase under an external electric field, making them promising candidates for electronic energy storage and solid-state refrigeration. Additionally, the field-induced strain in AFE materials is contingent upon the direction of the electric field, rendering it with a switching characteristic. Although AFE materials have made progress in the field of energy storage and negative electrocaloric effect, the coexistence of AFE and ferroelasticity is still rarely reported. Here, two isomorphic organic-inorganic hybrid perovskites, HDAEPbCl4 and HDAEPbBr4 (HDAE is [2-(hydroxydimethylammonio)ethan-1-aminium]), exhibiting FE-AFE-PE (PE is paraelectric) phase transitions, are presented. Remarkably, the temperature range where AFE and ferroelasticity coexist is significantly broadened from 59.9 K to 115.1 K by strengthening short-range forces via halogen substitution. This discovery extends the family of FE, AFE, and ferroelastic materials, contributing to the development of multifunctional materials and advancing multifunctional material development.

Blistering Behavior of Beryllium and Beryllium Alloy under High-Dose Helium Ion Irradiation.

Beryllium (Be) has been selected as the solid neutron multiplier material for a tritium breeding blanket module in ITER, which is also the primary option of the Chinese TBM program. But the irradiation swelling of beryllium is severe under high temperature, high irradiation damage and high doses of transmutation-induced helium. Advanced neutron multipliers with high stability at high temperature are desired for the demonstration power plant (DEMO) reactors and the China Fusion Engineering Test Reactor (CFETR). Beryllium alloys mainly composed of Be12M (M is W or Ti) phase were fabricated by HIP, which has a high melting point and high beryllium content. Beryllium and beryllide (Be12Ti and Be12W) samples were irradiated by helium ion with 30 keV and 1 × 1018 cm-2 at RT. The microstructures of Be, Be12Ti and Be12W samples were analyzed by SEM and TEM before and after ion irradiation. The average size of the first blistering on the surface of Be-W alloy is about 0.8 µm, and that of secondary blistering is about 79 nm. The surface blistering rates of the beryllium and beryllide samples were also compared. These results may provide a preliminary experimental basis for evaluating the irradiation swelling resistance of beryllium alloy.

Bovine colostrum prevents formula-induced gut microbiota dysbiosis in preterm pigs.

BACKGROUND: Preterm birth and formula feeding increase the risk of necrotizing enterocolitis (NEC), a gut inflammatory disease known to be associated with gut microbiota (GM) changes in infants. Supplemental bovine colostrum may protect against formula-induced NEC via GM changes. We hypothesised that feeding colostrum before, after, or during formula feeding affects NEC sensitivity via changes to GM. METHODS: Colonic GM (profiled by 16S ribosomal RNA gene amplicon sequencing) was compared in preterm pigs fed colostrum for 4 days, either before, after, or together with formula feeding for 4 days. Correlations between GM and gut parameters were assessed on day 5 or 9. RESULTS: Both exclusive and partial colostrum feeding induced higher GM diversity, lower Enterococcus abundance, and improved intestinal maturation parameters (villus structure, digestive enzyme activities, permeability), relative to exclusive formula feeding (all p < 0.05). Across feeding regimens, Enterococcus abundance was inversely correlated with intestinal maturation parameters. Conversely, there was no correlation between GM changes and early NEC lesions. CONCLUSION: Bovine colostrum inhibits formula-induced Enterococcus overgrowth and gut dysfunctions just after preterm birth but these effects are not causally linked. Optimising diet-related host responses, not GM, may be critical to prevent NEC in preterm newborn pigs and infants. IMPACT: Supplement of bovine colostrum to formula feeding modified the gut microbiota by increasing species diversity and reducing Enterococcus abundance, while concurrently improving intestinal functions in preterm pigs. Diet-related changes to the gut microbiota were not clearly associated with development of necrotizing enterocolitis (NEC) in preterm pigs, suggesting that diet-related gut microbiota effects are not critical for diet-related NEC protection. The study highlights the potential to use bovine colostrum as a supplement to formula feeding for preterm infants lacking human milk.

Establishment of Cephalic Index by Computed Tomography in Sampled Chinese Children.

OBJECTIVE: Cephalic Index (CI), the ratio of head width to length, is one of the indexes reflecting cranial morphological characteristics. Current norms were established by European and American countries. The purpose of the study was to study anthropometry of cranial parameters using computed tomography scans to establish the CI of the sampled Chinese Children. METHODS: The cross-sectional study was carried out on patients of age younger than 14 years old at Shanghai Children's Medical Center. The measurement of maximum cranial breadth and maximum cranial length were taken on a computed tomography scan machine and recorded for analysis. Cephalic Index was calculated for each age and sex group and compared with previously established norms. RESULTS: Five hundred eighteen patients met the inclusion criteria, including 301 males and 217 females. The means for boys and girls were 87.1 (SD: 4.3) and 85.8 (SD: 4.3), respectively. There was a significant difference between boys and girls (P < 0.01). Cephalic Index in different ages and on applying the 1-way analysis of variance association was statistically insignificant (P = 0.19). CONCLUSIONS: Chinese head shape was brachycephalic. A statistically significant correlation was seen between the CI and sex, while not age.

Pulsatile gonadotropin-releasing hormone therapy induces spermatogenesis in pituitary stalk interruption syndrome: A case report and review of the literature.

BACKGROUND: Pituitary stalk interruption syndrome (PSIS) is a rare anatomical defect of the pituitary gland falling under the spectrum of holoprosencephaly phenotypes. It is characterized by a deficiency in anterior pituitary hormones, such as growth hormone, gonadotropins, and thyroid hormones. Due to the syndrome's rarity and nonspecific manifestations, there is a lack of standardized treatment strategies. Consequently, early diagnosis through imaging and on-time intervention are crucial for improving patients' outcomes. CASE SUMMARY: A 30-year-old man presented with absent secondary sexual characteristics and azoospermia. Laboratory evaluation revealed a deficiency in gonadotropins, while thyroid function was mostly within normal ranges. Magnetic resonance imaging of the pituitary gland showed pituitary stalk agenesis, hypoplasia of the anterior pituitary, and ectopic posterior pituitary, leading to the diagnosis of PSIS. Initially, the patient underwent 6 mo of gonadotropin therapy without significant changes in hormone levels and secondary sexual characteristics. Pulsatile gonadotropin-releasing hormone therapy was then administered, resulting in the detection of sperm in the semen analysis within 3 mo. After 6 mo, routine semen tests showed normal semen quality. The couple faced challenges in conceiving due to abstinence and underwent three cycles of artificial insemination, which was unsuccessful. They also attempted in vitro fertilization, but unfortunately, the woman experienced a miscarriage 10 wk after the embryo transfer. CONCLUSION: Early detection, accurate diagnosis, and timely treatment are crucial in improving the quality of life and fertility of PSIS patients.

Intrauterine hyperglycaemia during late gestation caused mitochondrial dysfunction in skeletal muscle of male offspring through CREB/PGC1A signaling.

BACKGROUND: Maternal diabetes mellitus can influence the development of offspring. Gestational diabetes mellitus (GDM) creates a short-term intrauterine hyperglycaemic environment in offspring, leading to glucose intolerance in later life, but the long-term effects and specific mechanism involved in skeletal muscle dysfunction in offspring remain to be clarified. METHODS: Pregnant mice were divided into two groups: The GDM group was intraperitoneally injected with 100 mg/kg streptozotocin on gestational days (GDs) 6.5 and 12.5, while the control (CTR) group was treated with vehicle buffer. Only pregnant mice whose random blood glucose level was higher than 16.8 mmol/L beginning on GD13.5 were regarded as the GDM group. The growth of the offspring was monitored, and the glucose tolerance test was performed at different time points. Body composition analysis and immunohistochemical methods were used to evaluate the development of lean mass at 8 weeks. The exercise capacity and grip strength of the male mouse offspring were assessed at the same period. Transmission electron microscopy was used to observe the morphology inside skeletal muscle at 8 weeks and as a foetus. The genes and proteins associated with mitochondrial biogenesis and oxidative metabolism were investigated. We also coanalyzed RNA sequencing and proteomics data to explore the underlying mechanism. Chromatin immunoprecipitation and bisulfite-converted DNA methylation detection were performed to evaluate this phenomenon. RESULTS: Short-term intrauterine hyperglycaemia inhibited the growth and reduced the lean mass of male offspring, leading to decreased endurance exercise capacity. The myofiber composition of the tibialis anterior muscle of GDM male offspring became more glycolytic and less oxidative. The morphology and function of mitochondria in the skeletal muscle of GDM male offspring were destroyed, and coanalysis of RNA sequencing and proteomics of foetal skeletal muscle showed that mitochondrial elements and lipid oxidation were consistently impaired. In vivo and in vitro myoblast experiments also demonstrated that high glucose concentrations impeded mitochondrial organisation and function. Importantly, the transcription of genes associated with mitochondrial biogenesis and oxidative metabolism decreased at 8 weeks and during the foetal period. We predicted Ppargc1α as a key upstream regulator with the help of IPA software. The proteins and mRNA levels of Ppargc1α in the skeletal muscle of GDM male offspring were decreased as a foetus (CTR vs. GDM, 1.004 vs. 0.665, p = 0.002), at 6 weeks (1.018 vs. 0.511, p = 0.023) and 8 weeks (1.006 vs. 0.596, p = 0.018). In addition, CREB phosphorylation was inhibited in GDM group, with fewer activated pCREB proteins binding to the CRE element of Ppargc1α (1.042 vs. 0.681, p = 0.037), Pck1 (1.091 vs. 0.432, p = 0.014) and G6pc (1.118 vs. 0.472, p = 0.027), resulting in their decreased transcription. Interestingly, we found that sarcopenia and mitochondrial dysfunction could even be inherited by the next generation. CONCLUSIONS: Short-term intrauterine hyperglycaemia significantly reduced lean mass in male offspring at 8 weeks, resulting in decreased exercise endurance and metabolic disorders. Disrupted organisation and function of the mitochondria in skeletal muscle were also observed among them. Foetal exposure to hyperglycaemia decreased the ratio of phosphorylated CREB and reduced the transcription of Ppargc1α, which inhibited the transcription of downstream genes involving in mitochondrial biogenesis and oxidative metabolism. Abnormal mitochondria, which might be transmitted through aberrant gametes, were also observed in the F2 generation.

Double-stranded RNA induces antiviral transcriptional response through the Dicer-2/Ampk/FoxO axis in an arthropod.

Invertebrates mainly rely on sequence-specific RNA interference (RNAi) to resist viral infections. Increasing studies show that double-stranded RNA (dsRNA) can induce sequence-independent protection and that Dicer-2, the key RNAi player that cleaves long dsRNA into small interfering RNA (siRNA), is necessary for this protection. However, how this protection occurs remains unknown. Herein, we report that it is caused by adenosine triphosphate (ATP)-hydrolysis accompanying the dsRNA-cleavage. Dicer-2 helicase domain is ATP-dependent; therefore, the cleavage consumes ATP. ATP depletion activates adenosine monophosphate-activated protein kinase (Ampk) and induces nuclear localization of Fork head box O (FoxO), a key transcriptional factor for dsRNA-induced genes. siRNAs that do not require processing cannot activate the transcriptional response. This study reveals a unique nonspecific antiviral mechanism other than the specific RNAi in shrimp. This mechanism is functionally similar to, but mechanistically different from, the dsRNA-activated antiviral response in vertebrates and suggests an interesting evolution of innate antiviral immunity.

The effect of the molecular weight of blackberry polysaccharides on gut microbiota modulation and hypoglycemic effect in vivo.

Blackberry polysaccharides with certain molecular weight distribution have good bioactivity. In this research, type 2 diabetes mice were used to investigate the hypoglycemic effect of blackberry polysaccharides with three different molecular weights, BBP (603.59 kDa), BBP-8 (408.13 kDa) and BBP-24 (247.62 kDa), through gut microbiota modulation. Blackberry polysaccharides exhibited stronger hypoglycemic activity after degradation, and the FBG of BBP, BBP-8 and BBP-24 was reduced to 20.21 ± 4.17 mmol L-1, 20.6 ± 7.23 mmol L-1 and 17.32 ± 6.59 mmol L-1 and OGTT-AUC was reduced by 14.76%, 19.80% and 25.04%, respectively, after 8-week intervention. Furthermore, 16S rRNA gene sequencing analysis indicated that BBP, BBP-8 and BBP-24 could reshape the diversity and composition of the gut microbiota. From 0 to 4 weeks, the F/B of BBP, BBP-8 and BBP-24 reduced by 56.44%, 47.19% and 62.04%, reaching 3.39, 6.54, and 3.11 in the 8th week, respectively, which suggested the faster utilization of BBP-24. Moreover, the intervention the three blackberry polysaccharides increased the relative abundance of the targeted beneficial bacteria Oscillospira and Bacteroidaceae Bacteroides and decreased the relative abundance of the pathogenic bacterium Allobaculum. In general, the result demonstrated that blackberry polysaccharides with a lower molecular weight are more easily fermented, making the theoretical basis for the development of blackberry polysaccharides as a probiotic food to rapidly regulate intestinal flora for type 2 diabetes.