A Meta-analysis of the Effect of Noninvasive Brain Stimulation on Dysphagia in Patients with Cerebral Stroke.

The objective of this study is to assess the efficacy of non-invasive brain stimulation (NIBS) in preventing and treating dysphagia in patients who have experienced a cerebral stroke (CS). Both Chinese and international guidelines for the management of dysphagia resulting from CS mention various non-pharmacological treatments, such as acupuncture, mechanical myoelectric stimulation, and NIBS. However, due to limited evidence, these treatments are often suggested as measures rather than interventions. Therefore, this study assesses the impact of NIBS on the severity and improvement of dysphagia in CS patients. The researchers provide evidence-based recommendations for clinical practice by conducting a comprehensive literature review and meta-analysis. The researchers analyze the impact of NIBS on the severity of dysphagia and its overall improvement in CS patients. Employing a systematic computer-based search, the researchers retrieved randomized controlled trials and cohort studies published between the inception of relevant databases and December 1, 2022, about the utilization of NIBS in managing dysphagia in CS patients. This effort included nine articles for meta-analysis, with sample sizes ranging from 14 to 59, allowing an assessment of the effectiveness of NIBS in CS patients. The analysis revealed a mean difference (MD) score of 1.05 in the NIBS studies for the prevention and treatment of dysphagia severity in stroke patients, indicating a notable alleviation of dysphagia severity in CS patients through NIBS. The MD for the dysphagia score was also 1.05, and the MD for the functional dysphagia score was 1.78, suggesting that NIBS provided relief from dysphagia in CS patients. In summary, this meta-analysis thoroughly evaluated NIBS efficacy in CS patients and provided evidence-based recommendations for clinical practice. Future research needs to collect additional indicators to elucidate the nuances of various interventions, contributing to a more robust theoretical foundation for clinical therapy.

Electrocatalytic Interconversions of CO2 and Formate on a Versatile Iron-Thiolate Platform.

Exploring bidirectional CO2/HCO2- catalysis holds significant potential in constructing integrated (photo)electrochemical formate fuel cells for energy storage and applications. Herein, we report selective CO2/HCO2- electrochemical interconversion by exploiting the flexible coordination modes and rich redox properties of a versatile iron-thiolate platform, Cp*Fe(II)L (L = 1,2-Ph2PC6H4S-). Upon oxidation, this iron complex undergoes formate binding to generate a diferric formate complex, [(L-)2Fe(III)(µ-HCO2)Fe(III)]+, which exhibits remarkable electrocatalytic performance for the HCO2--to-CO2 transformation with a maximum turnover frequency (TOFmax) ∼103 s-1 and a Faraday efficiency (FE) ∼92(±4)%. Conversely, this iron system also allows for reduction at -1.85 V (vs Fc+/0) and exhibits an impressive FE ∼93 (±3)% for the CO2-to-HCO2- conversion. Mechanism studies revealed that the HCO2--to-CO2 electrocatalysis passes through dicationic [(L2)-•Fe(III)(µ-HCO2)Fe(III)]2+ generated by unconventional oxidation of the diferric formate species taking place at ligand L, while the CO2-to-HCO2- reduction involves a critical intermediate of [Fe(II)-H]- that was independently synthesized and structurally characterized.

Discovery of pyranonaphthoquinones and an eighteen-membered ring macrolide from the rhizospheric soil-derived fungus Phialocephala sp. YUD18001 by OSMAC strategy.

Two new pyranonaphthoquinones, phialoyxinones A (1) and B (2), a new eighteen-membered ring lactone, phialoyxtone (3), and five known pyranonaphthoquinone derivatives were identified from the fungus Phialocephala sp. YUD18001, which was isolated from the rhizospheric soil associated with Gastrodia elata. Their structures were unequivocally established by a comprehensive interpretation of the spectroscopic data, with the stereochemistry for 1-3 was defined by a combination of TDDFT calculations, and the DP4+ probability analysis based on NMR chemical shift calculations. All of the new compounds 1-3 were evaluated for cytotoxicity and acetylcholinesterase inhibitory, compound 2 exhibited in vitro cytotoxic activities against five human cancer cell lines (HL-60, SMMC-7721, A549, MCF-7 and SW480) with IC50 values ranging from 11.80 to 19.32 µM. Compounds 2 and 3 exhibited moderate AChE inhibitory activities. A putative biosynthetic pathway for the pyranonaphthoquinones was proposed.

Pathological pathway analysis in an experimental rheumatoid arthritis model and the tissue repair effect of acupuncture at ST36.

Rheumatoid arthritis (RA) is an autoimmune disease that generally affects the joints. In the face of inflammation-induced cartilage and bone damage, RA treatment remains insufficient. While research evidence indicates that acupuncture can exert anti-inflammatory and analgesic effects, improve the joint function of RA patients, and delay the disease, data on whether it can promote RA repair are lacking. Findings from the present work demonstrated that both the antigen-induced arthritis (AIA) and collagen-induced arthritis (CIA) models can simulate joint swelling of RA. The AIA model was more stable than the CIA model, with a higher incidence of successful arthritis modeling. Moreover, the AIA mice model could simulate the signal molecules and related pathological processes of the autoimmune response in RA, as well as major pathways related to RA and antigen immune response mechanisms. Manual acupuncture (MA) at Zusanli (ST36) significantly improved paw redness and swelling, pain, and inflammatory cell infiltration in the joints in AIA mice. The therapeutic effect of MA on AIA is achieved primarily through the regulation of steroid hormone biosynthesis, cell metabolism, and tissue repair processes. MA at ST36 can increase the gene contents of tissue repair growth factors, including PEG3, GADD45A, GDF5, FGF5, SOX2, and ATP6V1C2 in the inflammatory side joints of AIA mice, as well as the gene expression of the anti-inflammatory cytokine IL-10. In conclusion, acupuncture may alleviate RA in the joints via modulating the tissue healing process.

Castor oil-based waterborne polyurethane/tunicate cellulose nanocrystals nanocomposites for wearable strain sensors.

In this study, tunicate cellulose nanocrystals (TCNCs) were introduced into castor oil-based waterborne polyurethane (WPU) to prepare bio-based nanocomposites through a simple solution blending method. The effect of TCNCs content on the particle size and stability of the composite dispersions, as well as the thermophysical and mechanical properties of the composite films were studied and discussed. The unique structure and properties of TCNCs, such as high crystallinity, large aspect ratio and high modulus, not only greatly improved the storage stability of WPU, but also showed significant reinforcing/toughening effects and excellent compatibility to WPU. By drip-coating silver nanowires (AgNWs) on the surface of the composite films, the flexible strain sensors were fabricated, which showed excellent sensitivity in monitoring human movement.

Scalable Production of Self-Toughening Plant Oil-Based Polyurethane Elastomers with Multistimuli-Responsive Functionalities.

Plant oils are becoming of high industrial importance due to the persisting challenges befalling with the utilization of fossil fuels. Thus, developing methodologies to produce multifunctional materials by taking advantage of the unique structure of plant oil is highly desired. In this study, castor oil served as a cross-linker and soft segments, by incorporating scalable rhodamine 6G derivatives, to systematically synthesize a series of smart polymers that possess self-toughening and multistimuli-responsive capabilities. The polyurethane elastomers showed 10 times and 60 times increases in tensile strength and toughness, respectively, in comparison with the unmodified polyurethane due to the existence of large amounts of hydrogen bonding, dynamic C-N spiro bonds, rigid benzene ring, and high cross-link densities. The novel polyurethane elastomers exhibited excellent reversible multichromic behaviors in response to light, pH, and mechanics. Notably, the resulting polyurethane elastomers exhibited ultrasensitive sustained photochromism with tunable white emission and rapid reversibility. This study provides a simple and effective strategy to utilize plant oil for multifunctional material preparation and paves the way to open access for application of plant oil-based products in a variety of industry applications, such as sensors, self-fitting tissue scaffolds, and switchable devices.

Effect of vitamin D supplementation on the incidence and prognosis of depression: An updated meta-analysis based on randomized controlled trials.

Background: There have been several controversies about the correlation between vitamin D and depression. This study aimed to investigate the relationship between vitamin D supplementation and the incidence and prognosis of depression and to analyze the latent effects of subgroups including population and supplement strategy. Methods: A systematic search for articles before July 2021 in databases (PubMed, EMBASE, Web of Science, and the Cochrane Library) was conducted to investigate the effect of vitamin D supplementation on the incidence and prognosis of depression. Results: This meta-analysis included 29 studies with 4,504 participants, indicating that the use of vitamin D was beneficial to a decline in the incidence of depression (SMD: -0.23) and improvement of depression treatment (SMD: -0.92). Subgroup analysis revealed that people with low vitamin D levels (<50 nmol/L) and females could notably benefit from vitamin D in both prevention and treatment of depression. The effects of vitamin D with a daily supplementary dose of >2,800 IU and intervention duration of ≥8 weeks were considered significant in both prevention and treatment analyses. Intervention duration ≤8 weeks was recognized as effective in the treatment group. Conclusion: Our results demonstrate that vitamin D has a beneficial impact on both the incidence and the prognosis of depression. Whether suffering from depression or not, individuals with low vitamin D levels, dose >2,800 IU, intervention duration ≥8 weeks, and all females are most likely to benefit from vitamin D supplementation.

Targeted Recruitment and Degradation of Estrogen Receptor α by Photothermal Polydopamine Nanoparticles for Breast Tumor Ablation.

The major challenges of photothermal therapy (PTT) toward clinical application are the severe skin injury and inflammation response associated with high power laser irradiation. Herein, polydopamine nanoparticles (PDA-EST and PDA-RAL) targeted to estrogen receptor α (ERα) for efficient ablation of breast tumor under a low irradiation density of 0.1 W cm-2 are reported. These nanoparticles are capable of recruiting ERα on their surface and induce a complete ERα degradation via localized heat. Owing to the ERα targetability, PDA-EST and PDA-RAL strongly suppress the proliferation of breast cancer cells without causing significant inflammation. This work provides a generalized method for enhancing PTT efficacy under low irradiation density.

Dispositional Mindfulness and Post-traumatic Stress Symptoms in Emergency Nurses: Multiple Mediating Roles of Coping Styles and Emotional Exhaustion.

Objective: To explore the relationships between dispositional mindfulness (DM) and their post-traumatic stress symptoms (PTSS) of emergency nurses, and the mediating effects of coping styles and emotional exhaustion (EE). Methods: A cross-sectional survey study was conducted to collect data on DM, coping styles, EE, and PTSS among 571 emergency nurses from 20 hospitals in Chongqing, China. Correlation and structural equation models (SEMs) were used to evaluate the relationship among variables. Results: Emergency nurses with lower dispositional mindfulness, higher emotional exhaustion and preference for negative coping (NC) revealed more PTSS. The effect of NC on PTSS was partially mediated by emotional exhaustion. Negative coping and emotional exhaustion played concurrent and sequential mediating roles between dispositional mindfulness and PTSS. Conclusion: This study has made a significant contribution to existing literature. It was suggested to develop interventions aimed at enhancing mindfulness, reducing negative coping strategies, and alleviating emotional exhaustion, which may be effective at reducing or alleviating post-traumatic stress symptoms of emergency nurses.

Self-incompatibility requires GPI anchor remodeling by the poppy PGAP1 ortholog HLD1.

Glycosylphosphatidylinositol-anchored proteins (GPI-APs) are tethered to the outer leaflet of the plasma membrane where they function as key regulators of a plethora of biological processes in eukaryotes. Self-incompatibility (SI) plays a pivotal role regulating fertilization in higher plants through recognition and rejection of "self" pollen. Here, we used Arabidopsis thaliana lines that were engineered to be self-incompatible by expression of Papaver rhoeas SI determinants for an SI suppressor screen. We identify HLD1/AtPGAP1, an ortholog of the human GPI-inositol deacylase PGAP1, as a critical component required for the SI response. Besides a delay in flowering time, no developmental defects were observed in HLD1/AtPGAP1 knockout plants, but SI was completely abolished. We demonstrate that HLD1/AtPGAP1 functions as a GPI-inositol deacylase and that this GPI-remodeling activity is essential for SI. Using GFP-SKU5 as a representative GPI-AP, we show that the HLD1/AtPGAP1 mutation does not affect GPI-AP production and targeting but affects their cleavage and release from membranes in vivo. Our data not only implicate GPI-APs in SI, providing new directions to investigate SI mechanisms, but also identify a key functional role for GPI-AP remodeling by inositol deacylation in planta.

Innovative ochre processing and tool use in China 40,000 years ago.

Homo sapiens was present in northern Asia by around 40,000 years ago, having replaced archaic populations across Eurasia after episodes of earlier population expansions and interbreeding1-4. Cultural adaptations of the last Neanderthals, the Denisovans and the incoming populations of H. sapiens into Asia remain unknown1,5-7. Here we describe Xiamabei, a well-preserved, approximately 40,000-year-old archaeological site in northern China, which includes the earliest known ochre-processing feature in east Asia, a distinctive miniaturized lithic assemblage with bladelet-like tools bearing traces of hafting, and a bone tool. The cultural assembly of traits at Xiamabei is unique for Eastern Asia and does not correspond with those found at other archaeological site assemblages inhabited by archaic populations or those generally associated with the expansion of H. sapiens, such as the Initial Upper Palaeolithic8-10. The record of northern Asia supports a process of technological innovations and cultural diversification emerging in a period of hominin hybridization and admixture2,3,6,11.

Response of Milk Performance, Rumen and Hindgut Microbiome to Dietary Supplementation with Aspergillus oryzae Fermentation Extracts in Dairy Cows.

Fungal additives had beneficial effects on milk performance in dairy cows. Previous studies investigating the effects of fungal additives mainly focused on the rumen, such influences on the hindgut remain limited. This study aimed to investigate the effects of Aspergillus oryzae fermentation extracts (AOE) on the milk performance and microbiome in the rumen and hindgut using 16S rRNA gene sequencing. Twenty lactating multiparous Holstein cows were randomly assigned to control and treatment (5 g AOE per cow per day). The results showed that AOE increased the milk yield, milk protein and lactose concentration, but did not affect the milk fat concentration. Feeding AOE did not affect the ruminal VFA pattern, pH, NH3-N, and microbial cell protein production, but decreased lipopolysaccharide concentration and tended to decrease lactate concentration. The addition of AOE increased the fecal pH and the proportions of propionate, isovalerate and valerate, and decreased the acetate to propionate ratio. PCoA analysis showed that AOE did not affect the overall ruminal bacterial population composition. Only three genera changed slightly in relative abundance. In the feces, PCoA analysis showed that AOE changed the bacterial population composition. Feeding AOE increased the relative abundances of Ruminococcaceae UCG-010 and unclassified Clostridiales vadinBB60 group, and decreased Christensenellaceae R-7 group, unclassified Muribaculaceae, Prevotellaceae UCG-001 and Romboutsia. Spearman correlation showed unclassified Clostridiales vadinBB60 group was positively correlated with propionate proportion. Overall, we present that AOE not only functioned in rumen, but also in hindgut. The hindgut microbiome changes might play an important role in the milk performance improvement of dairy cows.

Electroacupuncture reactivates estrogen receptors to restore the neuroprotective effect of estrogen against cerebral ischemic stroke in long-term ovariectomized rats.

BACKGROUND: Stroke is a sexually dimorphic disease and a leading cause of death and disability. Estrogen replacement therapy (ERT) confers beneficial neuroprotective effects if administered within a widely accepted time window called the "critical period." However, very few studies have explored the idea of modulating the critical period to enable long-term post-menopausal women to regain more benefits from estrogen therapy. Here, motivated by previous findings that electroacupuncture could both alter estrogen metabolism and induce significant tolerance against stroke, it was explored whether EA could restore estrogen's neuroprotection against cerebral ischemia in long-term ovariectomized (OVX) rats. METHODS: We implemented 1 week(w)-EA pretreatment on OVX-10w or OVX-20w rats, and tested the expression of estrogen receptors, and detected the ERT's neuroprotection against stroke induced by middle cerebral artery occlusion (MCAO). RESULTS: We found that the expression levels of phospho-ERα-S118 and estrogen receptor ß (ERß) in the striatum of OVX-10w rats were significantly decreased and ERT's neuroprotection was abolished in the OVX-10w rats. However, EA-1w pretreatment could significantly recover the expression levels of phospho-ERα-S118 and ERß, and also restored the neuroprotective effects of ERT in OVX-10w rats. However, EA-1w pretreatment could not restore the expression of estrogen receptors and ERT's neuroprotection in OVX-20w rats. CONCLUSION: Taken together, our study indicates that EA may be an easy intervention that can restore the efficacy of estrogen therapy during the "critical period," which has the potential to improve the stroke outcomes of an enormous number of long-term post-menopausal women. However, the time-sensitive influences for how EA and estrogen metabolism interact with each other should be considered.

Luminescence chronology for the Paleolithic site of Xinmiaozhuang Locality 1 (XMZ1) in the Nihewan Basin, northern China, and its paleoenvironmental and archaeological implications.

In contrast to the prevailing view that the Chinese Paleolithic has been dominated by the Mode 1 technology-with a slow and conservative development from the Early to the Late Pleistocene-recent discoveries indicate that the lithic technology might have developed into an 'advanced' phase in some parts of China, at least since the early Late Pleistocene. The Xinmiaozhuang Locality 1 (XMZ1), located on the southern edge of the Nihewan Basin in northern China, is one of the examples belonging to such an 'advanced' phase. Although the stone artifacts at this site still belong to the long-existing 'small-tool' industry (core-and-flake) in this basin, some 'advanced' traits, including discoidal cores, elongated flakes, and 'Mousterian-like' triangular points and scrapers, are present. We provide a dating of the XMZ1 using the multiple elevated temperatures (MET) post infrared (pIR) infrared stimulated luminescence (IRSL) procedure (MET-pIRIR) on both multigrained single aliquots and 'individual' grains of potassium-rich feldspars (K-feldspars). The consistency between the single-aliquot and single-grain K-feldspar equivalent dose results mutually confirmed the reliability of the obtained ages. Our chronology indicates that the cultural layer falls within the period of ca. 63-75 ka, corresponding to the early stage of the Marine Isotope Stage (MIS) 4. Based on the correlation of the cultural age to the environmental proxies of loess and stalagmites from China, we suggest that the site might have witnessed dramatic fluctuations of paleoclimate during the site formation. Additionally, based on the discoidal cores distribution, a potential corridor along the Xuefeng-Wu-Tainhang-Great Khingan Mountains for ancient humans migrating between South and North China is suggested. However, more archaeological and chronological studies are required to figure out the origin and the dispersal patterns of the discoidal core associated with lithic assemblage and the tool-makers in East Asia.

Methyl-Donor Micronutrient for Gestating Sows: Effects on Gut Microbiota and Metabolome in Offspring Piglets.

This study aimed to investigate the effects of maternal methyl-donor micronutrient supplementation during gestation on gut microbiota and the fecal metabolic profile in offspring piglets. Forty-three Duroc × Erhualian gilts were assigned to two dietary groups during gestation: control diet (CON) and CON diet supplemented with MET (folic acid, methionine, choline, vitamin B6, and vitamin B12). The body weights of offspring piglets were recorded at birth and weaning. Besides this, fresh fecal samples of offspring piglets were collected at 7, 14, and 21 days. The gut microbiota composition, metabolic profile, and short-chain fatty acid (SCFA) profiles in the fecal samples were determined using 16S rDNA sequencing, liquid chromatography-mass spectrometry metabolomics, and gas chromatography methods, respectively. The results showed that maternal methyl-donor micronutrient supplementation increased the microbiota diversity and uniformity in feces of offspring piglets as indicated by increased Shannon and Simpson indices at 7 days, and greater Simpson, ACE, Chao1 and observed species indices at 21 days. Specifically, at the phylum level, the relative abundance of Firmicutes and the Firmicutes to Bacteroidetes ratio were elevated by maternal treatment. At the genus level, the relative abundance of SCFA-producing Dialister, Megasphaera, and Turicibacter, and lactate-producing Sharpea as well as Akkermansia, Weissella, and Pediococcus were increased in the MET group. The metabolic analyses show that maternal methyl-donor micronutrient addition increased the concentrations of individual and total SCFAs of 21-day piglets and increased metabolism mainly involving amino acids, pyrimidine, and purine biosynthesis. Collectively, maternal methyl-donor micronutrient addition altered gut microbiota and the fecal metabolic profile, resulting in an improved weaning weight of offspring piglets.

The role of Methanomassiliicoccales in trimethylamine metabolism in the rumen of dairy cows.

A considerable amount of trimethylamine (TMA) is likely generated in the rumen; however, its metabolism is still unclear. This study aimed to investigate the role of Methanomassiliicoccales (Mmc) in TMA metabolism in the rumen of dairy cows. Three experiments, two rumen in vitro fermentation trials and one dairy cow in vivo trial, were conducted. Four groups were set in Experiment 1: control, nitroglycerin (NG, a methanogen inhibitor), TMA (7.2 mmol/L), and TMA + NG. The methanogenic activity was completely inhibited in the NG group, and no methane production was observed in the NG and TMA + NG groups. The TMA content hardly reduced in the TMA + NG group (6.9 mmol/L) following a 2 d-incubation; in contrast, it demonstrated a significant reduction by 47.2% in the TMA group. Methanogen 16S rRNA gene sequencing and real-time PCR showed that the relative abundance of Mmc increased in the TMA group (P = 0.005). The increase was mainly attributed to two species-level taxa, Group 9 sp. ISO4-G1 and Group 10 sp. Four groups were set in Experiment 2: control, NG, choline (choline chloride, 7.2 mmol/L), and choline + NG. Choline was completely degraded in 24 h, and the TMA content reached the peak point (7.3 mmol/L) in the fermentation culture. The TMA content remained relatively stable in the choline + NG group following the peak point. However, it started to decrease after 24 h in the choline group, corresponding to the rapid increase in methane production and the abundance of Mmc. Eight mid-lactating, rumen-fistulated Holstein cows were randomly assigned to the control (n = 4) or choline (n = 4) group in Experiment 3: In the choline group, cows were gradually supplemented with 100-250 g/(cow·d) of choline chloride over 4 weeks. Compared to the control group, TMA accumulated in the rumen fluid, and the abundance of Mmc 16S rRNA gene and choline-degrading bacterial cutC gene increased in the rumen content in the choline group (P < 0.050). The trimethylamine N-oxide content in the plasma and milk of the dairy cows was approximately 10 times higher in the choline group than that in the control at the end of the experiment. These findings revealed that Mmc played an important role in the elimination of TMA in the rumen. The accumulation of TMA in the rumen would lead to a large amount of TMA absorbed into the blood stream of the dairy cows.

Inhalable Jojoba Oil Dry Nanoemulsion Powders for the Treatment of Lipopolysaccharide- or H2O2-Induced Acute Lung Injury.

Jojoba (Simmondsia chinensis (Link) C.K. Schneid) is a dioecious plant in desert and semi-desert areas, e.g., the Ismailia Desert in Egypt. Jojoba oil (JJBO) is a natural slight yellow oil with the functions of skin barrier repairing and wound healing, which is dermally applied as a traditional medication or cosmetic in the Middle East. The objective of this study was to prepare JJBO dry nanoemulsion powders (JNDs) and investigate their anti-acute lung injury effects. JJBO nanoemulsions (JNEs) were prepared and then lyophilized to JNDs and the properties and simulated lung deposition were measured. Rat acute lung injury (ALI) models were established after intratracheal (i.t.) administration of lipopolysaccharide (LPS) or hydrogen peroxide (H2O2). JNDs and dexamethasone (DXM) solutions were also i.t. administered to the rats. The pathological states of lung tissues were checked. Inflammatory and oxidative factors in the lung tissues were determined using ELISA methods. NF-κB p65 and caspase-3 were measured with a Western blotting method and an immunohistochemical method, respectively. JNDs had an appropriate mass median aerodynamic diameter (MMAD) of 4.17 µm and a fine particle fraction (FPF) of 39.11%. JNDs showed higher anti-inflammatory effect on LPS-induced ALI than DXM with a decrease in total protein content and down-regulation of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and NF-κB p65. JNDs also showed higher anti-inflammatory and anti-oxidation effect on H2O2-induced ALI than DXM with elimination of reactive oxygen species (ROS), increasing of superoxide dismutase (SOD), decrease in of lipid peroxide malondialdehyde (MDA) and glutathione (GSH), and inhibition of caspase-3 expression. Moreover, i.t. JNDs attenuated bleeding and infiltrations of the inflammatory cells in the two ALI models. JNDs are a promising natural oil-contained inhalable medication for the treatment of LPS- or H2O2-induced ALI.

Maternal Methyl-Donor Micronutrient Supplementation During Pregnancy Promotes Skeletal Muscle Differentiation and Maturity in Newborn and Weaning Pigs.

Adequate maternal methyl-donor micronutrient (MET) intake is an important determinant of the organ development and metabolic renovation of offspring. The mechanism involved in skeletal myogenesis and the effect of MET supplementation during pregnancy on the maternal body remain unclear. Thus, this study aimed to investigate the potential effect of methyl donor micronutrients (MET) on skeletal muscle development and metabolism in offspring using pig models. Forty-three Duroc × Erhualian gilts were assigned to two dietary groups during gestation: control diet (CON) and CON diet supplemented with MET (folic acid, methionine, choline, vitamin B6, and vitamin B12). The results showed that maternal MET exposure during pregnancy significantly increased the concentrations of protein, triiodothyronine (T3), and thyroxine (T4) in colostrum and methyl metabolites, including S-adenosylmethionine (SAM), S-adenosyl-L-homocysteine (SAH), 5-methyl-tetrahydrofolate (5-MTHF), and betaine, in the maternal and offspring umbilical vein serum. A similar pattern was demonstrated in the body weight gain and myofiber diameters in offspring. In addition, maternal MET supplementation significantly increased the concentration of offspring serum insulin-like growth factor 1 (IGF-1), T3, and T4; upregulated the mRNA expression of IGF-1 and IGF-1 receptor (IGF-1r) and the phosphorylation level of protein kinases in offspring longissimus dorsi muscle; and upregulated the expression of myogenic genes and fast myosin heavy chain (fast MyHC) in offspring skeletal muscle. Supplementing sows with higher levels of MET during gestation may promote skeletal muscle differentiation and maturity and improve the skeletal muscle mass of the piglets.

Design, Synthesis, and Biological Evaluation of Linear Aliphatic Amine-Linked Triaryl Derivatives as Potent Small-Molecule Inhibitors of the Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Interaction with Promising Antitumor Effects In Vivo.

A series of novel linear aliphatic amine-linked triaryl derivatives as inhibitors of PD-1/PD-L1 were designed, synthesized, and evaluated in vitro and in vivo. In this chemical series, compound 58 showed the most potent inhibitory activity and binding affinity with hPD-L1, with an IC50 value of 12 nM and a KD value of 16.2 pM, showing a binding potency approximately 2000-fold that of hPD-1. Compound 58 could bind with hPD-L1 on the cellular surface and competitively block the interaction of hPD-1 with hPD-L1. In a T cell function assay, 58 restored the T cell function, leading to increased IFN-γ secretion. Moreover, in a humanized mouse model, compound 58 significantly inhibited tumor growth without obvious toxicity and showed moderate PK properties after intravenous injection. These results indicated that 58 is a promising lead for further development of small-molecule PD-1/PD-L1 inhibitors for cancer therapy.

Ectopic Expression of a Self-Incompatibility Module Triggers Growth Arrest and Cell Death in Vegetative Cells.

Self-incompatibility (SI) is used by many angiosperms to reject self-pollen and avoid inbreeding. In field poppy (Papaver rhoeas), SI recognition and rejection of self-pollen is facilitated by a female S-determinant, PrsS, and a male S-determinant, PrpS PrsS belongs to the cysteine-rich peptide family, whose members activate diverse signaling networks involved in plant growth, defense, and reproduction. PrsS and PrpS are tightly regulated and expressed solely in pistil and pollen cells, respectively. Interaction of cognate PrsS and PrpS triggers pollen tube growth inhibition and programmed cell death (PCD) of self-pollen. We previously demonstrated functional intergeneric transfer of PrpS and PrsS to Arabidopsis (Arabidopsis thaliana) pollen and pistil. Here, we show that PrpS and PrsS, when expressed ectopically, act as a bipartite module to trigger a self-recognition:self-destruct response in Arabidopsis independently of its reproductive context in vegetative cells. The addition of recombinant PrsS to seedling roots expressing the cognate PrpS resulted in hallmark features of the P rhoeas SI response, including S-specific growth inhibition and PCD of root cells. Moreover, inducible expression of PrsS in PrpS-expressing seedlings resulted in rapid death of the entire seedling. This demonstrates that, besides specifying SI, the bipartite PrpS-PrsS module can trigger growth arrest and cell death in vegetative cells. Heterologous, ectopic expression of a plant bipartite signaling module in plants has not been shown previously and, by extrapolation, our findings suggest that cysteine-rich peptides diversified for a variety of specialized functions, including the regulation of growth and PCD.