Isotopic and DNA analyses reveal multiscale PPNB mobility and migration across Southeastern Anatolia and the Southern Levant.

Growing reliance on animal and plant domestication in the Near East and beyond during the Pre-Pottery Neolithic B (PPNB) (the ninth to eighth millennium BC) has often been associated with a "revolutionary" social transformation from mobility toward more sedentary lifestyles. We are able to yield nuanced insights into the process of the Neolithization in the Near East based on a bioarchaeological approach integrating isotopic and archaeogenetic analyses on the bone remains recovered from Nevali Çori, a site occupied from the early PPNB in Turkey where some of the earliest evidence of animal and plant domestication emerged, and from Ba'ja, a typical late PPNB site in Jordan. In addition, we present the archaeological sequence of Nevali Çori together with newly generated radiocarbon dates. Our results are based on strontium (87Sr/86Sr), carbon, and oxygen (δ18O and δ13Ccarb) isotopic analyses conducted on 28 human and 29 animal individuals from the site of Nevali Çori. 87Sr/86Sr results indicate mobility and connection with the contemporaneous surrounding sites during the earlier PPNB prior to an apparent decline in this mobility at a time of growing reliance on domesticates. Genome-wide data from six human individuals from Nevali Çori and Ba'ja demonstrate a diverse gene pool at Nevali Çori that supports connectedness within the Fertile Crescent during the earlier phases of Neolithization and evidence of consanguineous union in the PPNB Ba'ja and the Iron Age Nevali Çori.

TAWFN: a deep learning framework for protein function prediction.

MOTIVATION: Proteins play pivotal roles in biological systems, and precise prediction of their functions is indispensable for practical applications. Despite the surge in protein sequence data facilitated by high-throughput techniques, unraveling the exact functionalities of proteins still demands considerable time and resources. Currently, numerous methods rely on protein sequences for prediction, while methods targeting protein structures are scarce, often employing convolutional neural networks (CNN) or graph convolutional networks (GCNs) individually. RESULTS: To address these challenges, our approach starts from protein structures and proposes a method that combines CNN and GCN into a unified framework called the two-model adaptive weight fusion network (TAWFN) for protein function prediction. First, amino acid contact maps and sequences are extracted from the protein structure. Then, the sequence is used to generate one-hot encoded features and deep semantic features. These features, along with the constructed graph, are fed into the adaptive graph convolutional networks (AGCN) module and the multi-layer convolutional neural network (MCNN) module as needed, resulting in preliminary classification outcomes. Finally, the preliminary classification results are inputted into the adaptive weight computation network, where adaptive weights are calculated to fuse the initial predictions from both networks, yielding the final prediction result. To evaluate the effectiveness of our method, experiments were conducted on the PDBset and AFset datasets. For molecular function, biological process, and cellular component tasks, TAWFN achieved area under the precision-recall curve (AUPR) values of 0.718, 0.385, and 0.488 respectively, with corresponding Fmax scores of 0.762, 0.628, and 0.693, and Smin scores of 0.326, 0.483, and 0.454. The experimental results demonstrate that TAWFN exhibits promising performance, outperforming existing methods. AVAILABILITY AND IMPLEMENTATION: The TAWFN source code can be found at: https://github.com/ss0830/TAWFN.

The Mutual Regulatory Role of Ferroptosis and Immunotherapy in Anti-tumor Therapy.

Ferroptosis is a form of cell death that is triggered by the presence of ferrous ions and is characterized by lipid peroxidation induced by these ions. The mechanism exhibits distinct morphological characteristics compared to apoptosis, autophagy, and necrosis. A notable aspect of ferroptosis is its ability to inhibit uncontrolled tumor replication and immortalization, especially in malignant, drug-resistant, and metastatic tumors. Additionally, immunotherapy, a novel therapeutic approach for tumors, has been found to have a reciprocal regulatory relationship with ferroptosis in the context of anti-tumor therapy. A comprehensive analysis of ferroptosis and immunotherapy in tumor therapy is presented in this paper, highlighting the potential for mutual adjuvant effects. Specifically, we discuss the mechanisms underlying ferroptosis and immunotherapy, emphasizing their ability to improve the tumor immune microenvironment and enhance immunotherapeutic effects. Furthermore, we investigate how immunotherapeutic factors may increase the sensitivity of tumor cells to ferroptosis. We aim to provide a prospective view of the promising value of combined ferroptosis and immunotherapy in anticancer therapy by elucidating the mutual regulatory network between each.

Oxidative Stress Initiates Receptor-Interacting Protein Kinase-3/Mixed Lineage Kinase Domain-Like-Mediated Corneal Epithelial Necroptosis and Nucleotide-Binding Oligomerization Domain-Like Receptor Protein 3 Inflammasome Signaling during Fungal Keratitis.

Fungal keratitis remains a major cause of severe visual loss in developing countries because of limited choices of therapy. The progression of fungal keratitis is a race between the innate immune system and the outgrowth of fungal conidia. Programmed necrosis (necroptosis), a type of proinflammatory cell death, has been recognized as a critical pathologic change in several diseases. However, the role and potential regulatory mechanisms of necroptosis have not been investigated in corneal diseases. The current study showed, for the first time, that fungal infection triggered significant corneal epithelial necroptosis in human/mouse/in vitro models. Moreover, a reduction in excessive reactive oxygen species release effectively prevented necroptosis. NLRP3 knockout did not affect necroptosis in vivo. In contrast, ablation of necroptosis via RIPK3 knockout significantly delayed migration and inhibited the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in macrophages, which enhanced the progression of fungal keratitis. Taking these findings together, the study indicated that overproduction of reactive oxygen species in fungal keratitis leads to significant necroptosis in the corneal epithelium. Furthermore, the necroptotic stimuli-mediated NLRP3 inflammasome serves as a driving force in host defense against fungal infection.

Dual Oxytocin Receptor-G Protein Signaling in the Autoregulation of Activities of Oxytocin Neurons.

Oxytocin (OT), a hypothalamic nonaneuropeptide, can extensively modulate mental and physical activities; however, the regulation of its secretion from hypothalamic OT neurons remains poorly understood. OT neuronal activity is generally modulated by neurochemical environment, synaptic inputs, astrocytic plasticity, and interneuronal interactions. By changing intracellular signals and ion channel activity, these extracellular factors dynamically regulate OT neuronal activity and OT release in a microdomain-specific manner. In this process, OT receptor (OTR) and OTR-coupled G proteins are pivotal, typically observed during lactation. Suckling-elicited somatodendritic release of OT causes sequential activation of Gq and Gs proteins to increase the firing rate gradually and trigger burst firing transiently, and then of Gi/o protein to cause post-burst inhibition as a result of potential bolus somatodendritic release of OT during the burst-like discharges. Under chronic social stress like mother-baby separation and cesarean section, excessive somatodendritic secretion of OT and over-excitation of OT neurons cause post-excitation inhibition of OT neuronal activity and reduction of OT secretion. In this process, dominance of G protein that couples to OTR is switched from Gq to Gi/o type because of inhibition of OTR-Gq signaling following negative feedback of downstream Gq signaling or crosstalk of Gq with Gs and Gi signals. This review summarizes our current understandings of OT/OTR signaling in the autoregulation of OT neuronal activity under physiological and pathological conditions.

Intranasal application of diluted saline alleviates ischemic brain injury in association with suppression of vasopressin neurons.

INTRODUCTION: Cerebral swelling and brain injury in ischemic stroke are closely related to increased vasopressin (VP) secretion. How to alleviate ischemic brain injury by suppressing VP hypersecretion through simply available approaches remains to be established. METHODS: Using a rat model of middle cerebral artery occlusion (MCAO), testing effects of intranasal application of 0.09% NaCl (IAL) on brain damages, VP neuronal activity, synaptic inputs, astrocytic plasticity, olfactory bulb (OB) activity in immunohistochemistry, patch-clamp recording, Western blotting and co-immunoprecipitation. RESULTS: IAL reduced MCAO-evoked neurological disorders, brain swelling, injury and loss of neurons, increase in c-Fos expression and excitation of supraoptic VP neurons. The effects of IAL on VP neurons were associated with its suppression of MCAO-evoked increase in the frequency of excitatory synaptic inputs and decrease in the expression of glial fibrillary acidic protein (GFAP) filaments around VP neurons. MCAO and IAL also caused similar but weaker reactions in putative oxytocin neurons. In the OB, MCAO also increased the firing rate of mitral cells in the lesioned side, which was reduced by IAL. Direct hypotonic challenge of OB slices increased the expression of glutamine synthetase and GFAP filaments in the glomerular bodies while reducing the firing rate of mitral cells. Blocking aquaporin 4 activity in the supraoptic and paraventricular nuclei in the MCAO side blocked MCAO-evoked VP increase and brain damages. CONCLUSION: IAL reduces ischemic stroke-evoked brain injury in association with suppressing VP neuronal activity through reducing excitatory synaptic inputs and astrocytic process retraction, which likely result from reducing mitral cell activation.

Insect herbivory on woody broadleaf seedlings along a subtropical elevational gradient supports the resource concentration hypothesis.

PREMISE: Theories of plant-herbivore interactions hold that seedlings are more vulnerable to herbivory in warmer and more stable climates at lower elevations. Hypotheses of plant apparency, resource concentration, and resource availability have been proposed to explain variability in leaf herbivory. However, seasonal differences in the effects of these hypotheses on leaf herbivory on seedlings remain unclear. METHODS: We evaluated the three herbivory hypotheses by comparing the percentage and frequency of leaf herbivory in understory broadleaf seedlings in a subtropical forest in May (spring) and October (autumn) along an elevational gradient (290-1370 m a.s.l.). In total, we measured 2890 leaves across 696 seedlings belonging to 95 species and used beta regressions to test the effects of plant apparency (e.g., leaf area, seedling height), resource concentration (e.g., plant species diversity), and resource availability (e.g., canopy openness, soil available N and P) on leaf herbivory. RESULTS: Seedlings exhibited unimodal patterns of leaf herbivory along elevation, with drivers of leaf herbivory varying by the month. Variation in the frequency of leaf herbivory was best explained by the resource concentration hypothesis (e.g., plant species diversity) in both months, and herbivory was lower on seedlings in sites with higher plant diversity. Plant apparency hypothesis (e.g., leaf area, seedling height) was weakly supported only in spring, and the evidence for resource availability hypothesis (e.g., canopy openness, soil nutrients) was mixed. CONCLUSIONS: This study supports the resource concentration hypothesis and reveals the importance of seasonal difference on understanding leaf herbivory patterns and the drivers of plant diversity in subtropical forests.

New insight into the effects of p-benzoquinone on photocatalytic reduction of Cr(VI) over Fe-doped g-C3N4.

It is of great significance to establish an effective method for removing Cr(VI) from wastewater. Herein, Fe-doped g-C3N4 (namely Fe-g-C3N4-2) was synthesized and then employed as photocatalyst to conduct the test of Cr(VI) reduction. Notably, the embedding of Fe ion in g-C3N4 can offer the Fe2+/Fe3+ redox couples, so reducing the interfacial resistance of charge transfer and suppressing the recombination of photogenerated electrons and holes. The impurity energy levels will form in g-C3N4 after the introduction of Fe ion, thereby boosting the light absorption capacity of catalyst. Thus, Fe-g-C3N4-2 showed good performance in photocatalytic Cr(VI) reduction, and the reduction efficiency of Cr(VI) can reach 39.9% within 40 min. Different with many previous studies, current work unexpectedly found that the addition of p-benzoquinone (BQ) can promote the Cr(VI) reduction, and the reduction efficiency of Cr(VI) over Fe-g-C3N4-2 was as high as 93.2% in the presence of BQ (1.5 mM). Further analyses showed that BQ can be reduced to hydroquinone (HQ) by photogenerated electrons, and UV light can also directly induce BQ to generate HQ by using H2O as the hydrogen donor. The HQ with reducing ability can accelerate the Cr(VI) reduction. In short, current work shared some novel insights into photocatalytic Cr(VI) reduction in the presence of BQ. Future research should consider possible reactions between photogenerated electrons and BQ. For the UV-induced photocatalysis, the suitability of BQ as the scavenger of O2•‒ must be given carefully consideration.

Bidirectional associations between sleep quality/duration and multimorbidity in middle-aged and older people Chinese adults: a longitudinal study.

BACKGROUND: Multimorbidity and sleep disorder possess high incidence rates in the middle-aged and older people populations, posing a significant threat to quality of life and physical and mental health. However, investigators have previously only analysed the unidirectional association between sleep status and multimorbidity. We aimed to investigate bidirectional associations between sleep quality or duration and multimorbidity in middle-aged and older Chinese adults from a longitudinal perspective. METHOD: We enrolled a total of 9823 participants 45 years and older from the China Health and Retirement Longitudinal Study from 2015 to 2018 in our study. Multimorbidity was defined as two or more coexisting chronic diseases in the same individual based on 14 self-reported disease questions. Sleep quality was classified as "good" (restless < 1 day per week) and "poor" (restless ≥ 1 days per week); and sleep duration was divided into short (< 6 h), medium (6-9 h), and long (> 9 h). The bidirectional association between multimorbidity and sleep condition was examined using multivariate logistic regression models with adjustments for covariates. RESULTS: Individuals with poor sleep quality showed a significantly higher prevalence of multimorbidity in the future. The adjusted OR (95% CI) values of individuals with poor sleep quality with respect to developing two diseases, three diseases, and ≥ 4 diseases were 1.39 (1.19, 1.63), 1.56 (1.23, 2.03), and 2.36 (1.68, 3.33), respectively. In addition, individuals with multimorbidity exhibited a significantly higher risk of poor sleep quality in the future. Short sleep duration led to multimorbidity in the future (OR = 1.49; 95 CI%, 1.37-1.63), while multimorbidity contributed to short sleep duration (< 6 h) in the future (OR = 1.39; 95% CI, 1.27-1.51) after full adjustment. CONCLUSIONS: There was a bidirectional association between sleep quality or short sleep duration and multimorbidity in middle-aged and older Chinese adults. We recommend that greater attention be given to clinical management among adults with sleep disorders or physical multimorbidities.

Risk of glaucoma to subsequent dementia or cognitive impairment: a systematic review and meta-analysis.

BACKGROUND: Substantial evidence supports that glaucoma and dementia share pathological mechanisms and pathogenic risk factors. However, the association between glaucoma, cognitive decline and dementia has yet to be elucidated. OBJECTIVE: This study was aimed to assess whether glaucoma increase the risk of dementia or cognitive impairment. METHODS: PubMed, Cochrane Library, Web of Science, and EMBASE databases for cohort or case-control studies were searched from inception to March 10, 2024. The Newcastle-Ottawa Quality Assessment Scale (NOS) was used to the risk of bias. Heterogeneity was rigorously evaluated using the I2 test, while publication bias was assessed by visual inspection of the funnel plot and by Egger' s regression asymmetry test. Subgroup analyses were applied to determine the sources of heterogeneity. RESULTS: Twenty-seven studies covering 9,061,675 individuals were included. Pooled analyses indicated that glaucoma increased the risk of all-cause dementia, Alzheimer's disease, vascular dementia, and cognitive impairment. Subgroup analysis showed that the prevalence of dementia was 2.90 (95% CI: 1.45-5.77) in age ≥ 65 years and 2.07 (95% CI: 1.18-3.62) in age<65 years; the incidence rates in female glaucoma patients was 1.46 (95% CI: 1.06-2.00), respectively, which was no statistical significance in male patients. Among glaucoma types, POAG was more likely to develop dementia and cognitive impairment. There were also differences in regional distribution, with the highest prevalence in the Asia region, while glaucoma was not associated with dementia in Europe and North America regions. CONCLUSION: Glaucoma increased the risk of subsequent cognitive impairment and dementia. The type of glaucoma, gender, age, and region composition of the study population may significantly affect the relationship between glaucoma and dementia.

Hybrid teaching after COVID-19: advantages, challenges and optimization strategies.

BACKGROUND: In the post-pandemic era of higher education, hybrid teaching has emerged as a prevalent approach and is anticipated to persist as a defining trend in the future teaching reforms worldwide. However, despite its widespread adoption, certain limitations have become apparent. The objective of this study is to identify the genuine factors that impact students' performance, explore strategies that teachers can employ to enhance their teaching effectiveness and enhance students' academic self-efficacy. METHODS: The study was performed among undergraduate medical students enrolled in Physiology course at Harbin Medical University in 2020 and 2022. Since 2020, influenced by the COVID-19 pandemic, a hybrid teaching method based on an established offline teaching model called BOPPPS was implemented. A questionnaire was performed in both 2020 and 2022 to evaluate students' satisfaction and efficiency of our hybrid teaching. A comparison was also carried out on the final examination scores of students majoring in Pharmacy and Clinical Pharmacy across the years 2020 to 2022. RESULTS: The final examination scores of students in 2022 were significantly lower than those in 2020 and 2021 both in Pharmacy and Clinical Pharmacy majors. There was also a decrease of the score in students of Clinical Pharmacy in 2021 compared to 2020. The questionnaire indicated that over half (52.0%) of the students in 2022 preferred offline teaching method, in contrast to 39.1% in 2020. There were obvious changes in students from 2020 to 2022 about the disadvantages of hybrid teaching, the improvement of students' learning ability and the duration of students' autonomous learning. Through cross statistical analysis, online learning styles, learning ability improvement and students' learning burden have been identified as the primary factors influencing their preference for future teaching method. CONCLUSIONS: Hybrid teaching is still a necessary trend in the future teaching reform base on its multiple advantages. However, in order to improve the teaching outcomes and foster students' participation and learning initiatives, it is imperative to undertake additional reforms in the future teaching process.

Interface coupling to improve O2 adsorption and accelerate charge separation for boosting photocatalytic performance of ZnO/ZnIn2S4 composite in H2O2 production and environmental remediation.

The key to heterogeneous photo-Fenton technology lies in the efficient generation of hydrogen peroxide (H2O2). Herein, a newly-designed ZnO/ZnIn2S4 composite with heterostructure is synthesized. Benefiting from the formation of built-in electric field, the recombination of photoinduced electrons and holes is suppressed and interfacial charge transfer resistance is reduced. Importantly, the embedding of ZnO in ZnIn2S4 can improve the hydrophobicity and create microscopic three-phase interface, thereby boosting the capture capability for O2 and providing the convenience for the occurrence of O2 reduction reaction. More interestingly, the existence of ZnIn2S4 in the ZnO/ZnIn2S4 composite can reduce the Gibbs free energy (ΔG) of key intermediate (OOH*) formation, which will accelerate the generation of H2O2. As a result, the ZnO/ZnIn2S4 composite displays excellent performance in photocatalytic H2O2 production, and the highest yield was about 897.6 µmol/g/h within 60 min under visible light irradiation. The transfer of photoinduced carriers follows the S-scheme type mechanism. The photogenerated holes can be captured by drug residues (i.e., diclofenac sodium) to accelerate H2O2 production, while generated H2O2 can combine with Fe2+ to construct photo-Fenton system for achieving the advanced degradation of diclofenac sodium, which was mainly related to the formation of OH•. Furthermore, generated H2O2 can be applied for performing the inactivation of pathogenic bacteria. In short, current work will provide a valuable reference for future research.

Oxyanion Engineering on RuO2 for Efficient Proton Exchange Membrane Water Electrolysis.

In acidic proton exchange membrane water electrolysis (PEMWE), the anode oxygen evolution reaction (OER) catalysts rely heavily on the expensive and scarce iridium-based materials. Ruthenium dioxide (RuO2) with lower price and higher OER activity, has been explored for the similar task, but has been restricted by the poor stability. Herein, we developed an anion modification strategy to improve the OER performance of RuO2 in acidic media. The designed multicomponent catalyst based on sulfate anchored on RuO2/MoO3 displays a low overpotential of 190 mV at 10 mA cm-2 and stably operates for 500 hours with a very low degradation rate of 20 µV h-1 in acidic electrolyte. When assembled in a PEMWE cell, this catalyst as an anode shows an excellent stability at 500 mA cm-2 for 150 h. Experimental and theoretical results revealed that MoO3 could stabilize sulfate anion on RuO2 surface to suppress its leaching during OER. Such MoO3-anchored sulfate not only reduces the formation energy of *OOH intermediate on RuO2, but also impedes both the surface Ru and lattice oxygen loss, thereby achieving the high OER activity and exceptional durability.

Contribution of inwardly rectifying K+ channel 4.1 of supraoptic astrocytes to the regulation of vasopressin neuronal activity by hypotonicity.

Astrocytic morphological plasticity and its modulation of adjacent neuronal activity are largely determined by astrocytic volume regulation, in which glial fibrillary acidic protein (GFAP), aquaporin 4 (AQP4), and potassium channels including inwardly rectifying K+ channel 4.1 (Kir4.1) are essential. However, associations of astrocyte-dominant Kir4.1 with other molecules in astrocytic volume regulation and the subsequent influence on neuronal activity remain unclear. Here, we report our study on these issues using primary cultures of rat pups' hypothalamic astrocytes and male adult rat brain slices. In astrocyte culture, hyposmotic challenge (HOC) significantly decreased GFAP monomer expression and astrocytic volume at 1.5 min and increased Kir4.1 expression and inwardly rectifying currents (IRCs) at 10 min. BaCl2 (100 µmol/l) suppressed the HOC-increased IRCs, which was simulated by VU0134992 (2 µmol/l), a Kir4.1 blocker. Preincubation of the astrocyte culture with TGN-020 (10 µmol/l, a specific AQP4 blocker) made the HOC-increased Kir4.1 currents insignificant. In hypothalamic brain slices, HOC initially decreased and then increased the firing rate of vasopressin (VP) neurons in the supraoptic nucleus. In the presence of BaCl2 or VU0134992, HOC-elicited rebound increase in VP neuronal activity was blocked. GFAP was molecularly associated with Kir4.1, which was increased by HOC at 20 min; this increase was blocked by BaCl2 . These results suggest that HOC-evoked astrocytic retraction or decrease in the volume and length of its processes is associated with increased Kir4.1 activity. Kir4.1 involvement in HOC-elicited astrocytic retraction is associated with AQP4 activity and GFAP plasticity, which together determines the rebound excitation of VP neurons.

A high-efficiency gene silencing in plants using two-hit asymmetrical artificial MicroRNAs.

MicroRNAs (miRNAs) are small non-coding RNA molecules that play a crucial role in gene regulation. They are produced through an enzyme-guided process called dicing and have an asymmetrical structure with two nucleotide overhangs at the 3' ends. Artificial microRNAs (amiRNAs or amiRs) are designed to mimic the structure of miRNAs and can be used to silence specific genes of interest. Traditionally, amiRNAs are designed based on an endogenous miRNA precursor with certain mismatches at specific positions to increase their efficiency. In this study, the authors modified the highly expressed miR168a in Arabidopsis thaliana by replacing the single miR168 stem-loop/duplex with tandem asymmetrical amiRNA duplexes that follow the statistical rules of miRNA secondary structures. These tandem amiRNA duplexes, called "two-hit" amiRNAs, were shown to have a higher efficiency in silencing GFP and endogenous PDS reporter genes compared to traditional "one-hit" amiRNAs. The authors also demonstrated the effectiveness of "two-hit" amiRNAs in silencing genes involved in miRNA, tasiRNA, and hormone signalling pathways, individually or in families. Importantly, "two-hit" amiRNAs were also able to over-express endogenous miRNAs for their functions. The authors compare "two-hit" amiRNA technology with CRISPR/Cas9 and provide a web-based amiRNA designer for easy design and wide application in plants and even animals.

Embryonic stem cell extracellular vesicles reverse the senescence of retinal pigment epithelial cells by the p38MAPK pathway.

Retinal pigment epithelial (RPE) cellular senescence is regarded as an initiator for age-related macular degeneration (AMD). We previously demonstrated that by the coculture way, embryonic stem cells (ESCs) can reverse the senescence of RPE cells, but xenograft cells can cause a plethora of adverse effects. Extracellular vesicles (EVs) derived from ESCs can act as messengers to mediate nearby cell activities and have the same potential as ESCs to reverse RPE senescence. Furthermore, ESC-EVs have achieved preliminary efficacy while treating many age-related diseases. The present study aimed to test the effect of ESC-EVs on the replicative senescence model of RPE cells as well as its mechanism. The results showed that ESC-EVs enhanced the proliferative ability and cell cycle transition of senescent RPE cells, whereas reduced the senescence-associated galactosidase (SA-ß-gal) staining rate, as well as the levels of mitochondrial membrane potential (MMP) and reactive oxygen species (ROS). Moreover, classical markers of cellular senescence p21WAF1/CIP1 (p21) and p16INK4a (p16) were downregulated. The bioinformatic analysis and further study showed that the inhibition of the p38MAPK pathway by ESC-EVs played a pivotal role in RPE cellular senescence-reversing effect, which was ameliorated or even abolished when dehydrocorydaline were administrated simultaneously, demonstrating that ESC-EVs can effectively reverse RPE cellular senesence by inhibiting the p38MAPK pathway, thus highlights the potential of ESC-derived EVs as biomaterials for preventative and protective therapy in AMD.

Excitatory Effects of Astrocytic Hydrogen Sulfide on the Electrical Activity of Oxytocin Neurons in the Supraoptic Nucleus.

INTRODUCTION: In the regulation of oxytocin (OT) neuronal activity, hydrogen sulfide (H2S), a gaseous neurotransmitter, likely exerts an excitatory role. This role is associated with increased expression of astrocytic cystathionine-ß-synthase (CBS), the key enzyme for H2S synthesis. However, it remains unclear whether H2S is mainly produced in astrocytes and contributes to the autoregulation of OT neurons. METHODS: In hypothalamic slices of male rats, OT and H2S-associated drug effects were observed on the firing activity and spontaneous excitatory postsynaptic currents (sEPSCs) of putative OT neurons in the supraoptic nucleus (SON) in whole-cell patch-clamp recording. Expression of glial fibrillary acidic protein (GFAP) in the SON was analyzed in Western blots. In addition, changes in the length of rat pups' hypothalamic astrocytic processes were observed in primary cultures. RESULTS: In brain slices, OT significantly increased the firing rate of OT neurons, which was simulated by CBS allosteric agonist S-adenosyl-L-methionine (SAM) and H2S slow-releasing donor GYY4137 but blocked by CBS inhibitor aminooxyacetic acid (AOAA). L-α-aminoadipic acid (a gliotoxin) blocked SAM-evoked excitation. OT and SAM also increased the frequency and amplitude of sEPSCs; the effect of OT was blocked by AOAA. Both OT and GYY4137 reduced GFAP expression in the SON. Morphologically, OT or GYY4137 time-dependently reduced the length of astrocytic processes in primary cultures. CONCLUSIONS: These findings indicate that the auto-excitatory effect of OT on OT neurons is mediated by H2S from astrocytes at least partially and astrocytic H2S can elicit retraction of astrocytic processes that subsequently increase OT neuronal excitability.

Physiological and iTRAQ-based quantitative proteomics analyses reveal the similarities and differences in stress responses between short-term boron deficiency and toxicity in wheat roots.

BACKGROUND: Boron (B) is a trace element that is essential for normal wheat development, such as root growth. In wheat, roots are important organs that absorb nutrients and water. However, at present, there is insufficient research on the molecular mechanism underlying how short-term B stress affects wheat root growth. METHODS AND RESULTS: Here, the optimal concentration of B for wheat root growth was determined, and the proteomic profiles of roots under short-term B deficiency and toxicity were analyzed and compared by the isobaric tag for relative and absolute quantitation (iTRAQ) technique. A total of 270 differentially abundant proteins (DAPs) that accumulated in response to B deficiency and 263 DAPs that accumulated in response to B toxicity were identified. Global expression analysis revealed that ethylene, auxin, abscisic acid (ABA), and Ca2+ signals were involved in the responses to these two stresses. Under B deficiency, DAPs related to auxin synthesis or signaling and DAPs involved in calcium signaling increased in abundance. In striking contrast, auxin and calcium signals were repressed under B toxicity. Twenty-one DAPs were detected under both conditions, including RAN1 that played a core role in the auxin and calcium signals. Overexpression of RAN1 was shown to confer plant resistance to B toxicity by activating auxin response genes, including TIR and those identified by iTRAQ in this research. Moreover, growth of the primary roots of tir mutant was significantly inhibited under B toxicity. CONCLUSION: Taken together, these results indicate that some connections were present between RAN1 and the auxin signaling pathway under B toxicity. Therefore, this research provides data for improving the understanding of the molecular mechanism underlying the response to B stress.

The Effectiveness of Mindfulness-Based Intervention on Emotional States of Women Undergoing Fertility Treatment: A Meta-Analysis.

For many infertile women, their inability to fulfill their aspirations and match society's expectations of motherhood may lead to mental illness. They frequently select in vitro fertilization (IVF) to achieve their wish to have children. In vitro fertilization is actually a multi-dimensional stressor. There are numerous psychological methods to assist patients decrease stress, among which mindfulness-based intervention is a prominent one. However, the effectiveness of mindfulness intervention in this group remains debatable. Therefore, our research seeks to evaluate the efficacy of mindfulness intervention in improving the emotional state of women undergoing in vitro fertilization by systematic review and meta-analysis, so as to provide a novel treatment plan for psychological therapy of this group. A meta-analysis was undertaken by scanning English databases PubMed, Embase, Cochrane library, Web of science, etc. Among them, the retrieval period is from the foundation of the database until July 5, 2022. Two investigators examined the literature according to the inclusion and exclusion criteria, and conducted meta-analysis using stata15.0 software. Six studies involving 964 infertile women were included. According to the meta-analysis, mindfulness was more effective than the control group in reducing anxiety, depression, and correlations in infertile women [standard mean difference, SMD = -0.31, 95% confidence interval (CI): -0.56 to -0.06], [SMD = -0.94, 95% CI: -1.84 to -0.03], [r = 0.38, 95% CI: 0.25-0.52]. In terms of mindfulness and self-compassion, there was no significant difference between the intervention and control groups [SMD = 0.73, 95% CI: -0.38 to -1.85], [SMD = 0.09, 95% CI: -0.19 to -0.37]. As an intervention strategy for infertile women with anxiety and despair, mindfulness intervention might be a treatment priority.

A Joint Acoustic Emission Source Localization Method for Composite Materials.

Damage localization methods for composite materials are a popular research topic at present. The time-difference-blind localization method and beamforming localization method are often individually utilized in the localization of the acoustic emission sources of composite materials. Based on the performances of the two methods, a joint localization method for the acoustic emission sources of composite materials is proposed in this paper. Firstly, the performance of the time-difference-blind localization method and the beamforming localization method were analyzed. Then, with the advantages and disadvantages of these two methods in mind, a joint localization method was proposed. Finally, the performance of the joint localization method was verified using simulations and experiments. The results show that the joint localization method can reduce the localization time by half compared with the beamforming localization method. At the same time, compared with the time-difference-blind localization method, the localization accuracy can be improved.