Host specificity of plant-associated bacteria is negatively associated with genome size and host abundance along a latitudinal gradient.

Host specialization plays a critical role in the ecology and evolution of plant-microbe symbiosis. Theory predicts that host specialization is associated with microbial genome streamlining and is influenced by the abundance of host species, both of which can vary across latitudes, leading to a latitudinal gradient in host specificity. Here, we quantified the host specificity and composition of plant-bacteria symbioses on leaves across 329 tree species spanning a latitudinal gradient. Our analysis revealed a predominance of host-specialized leaf bacteria. The degree of host specificity was negatively correlated with bacterial genome size and the local abundance of host plants. Additionally, we found an increased host specificity at lower latitudes, aligning with the high prevalence of small bacterial genomes and rare host species in the tropics. These findings underscore the importance of genome streamlining and host abundance in the evolution of host specificity in plant-associated bacteria along the latitudinal gradient.

A modified nucleoside O6-methyl-2'-deoxyguanosine-5'-triphosphate exhibits anti-glioblastoma activity in a caspase-independent manner.

Resistance to temozolomide (TMZ), the frontline chemotherapeutic agent for glioblastoma (GBM), has emerged as a formidable obstacle, underscoring the imperative to identify alternative therapeutic strategies to improve patient outcomes. In this study, we comprehensively evaluated a novel agent, O6-methyl-2'-deoxyguanosine-5'-triphosphate (O6-methyl-dGTP) for its anti-GBM activity both in vitro and in vivo. Notably, O6-methyl-dGTP exhibited pronounced cytotoxicity against GBM cells, including those resistant to TMZ and overexpressing O6-methylguanine-DNA methyltransferase (MGMT). Mechanistic investigations revealed that O6-methyl-dGTP could be incorporated into genomic DNA, disrupting nucleotide pools balance, and inducing replication stress, resulting in S-phase arrest and DNA damage. The compound exerted its anti-tumor properties through the activation of AIF-mediated apoptosis and the parthanatos pathway. In vivo studies using U251 and Ln229 cell xenografts supported the robust tumor-inhibitory capacity of O6-methyl-dGTP. In an orthotopic transplantation model with U87MG cells, O6-methyl-dGTP showcased marginally superior tumor-suppressive activity compared to TMZ. In summary, our research, for the first time, underscores the potential of O6-methyl-dGTP as an effective candidate against GBM, laying a robust scientific groundwork for its potential clinical adoption in GBM treatment regimens.

Mussel-inspired adhesive and anti-swelling hydrogels for underwater strain sensing.

The application of hydrogels in an underwater environment is limited due to their swelling behavior and the existence of a hydration layer. In this study, a hydrogel based on poly(sulfobetaine methacrylate) (PSBMA), tannic acid (TA) and montmorillonite (MMT) was prepared with excellent anti-swelling properties and underwater self-adhesion properties. The PSBMA hydrogel has excellent anti-swelling properties due to the strong electrostatic interaction between charged groups of PSBMA chains. Inspired by marine mussels, tannic acid modified montmorillonite (TA@MMT) was introduced. Natural polyphenol tannic acid, as a catechol donor, provides a large number of catechol groups for hydrogels. Montmorillonite acts as the physical cross-linking point of PSBMA chains through electrostatic interaction to improve the cohesion of the hydrogel. By combining the adhesion mechanism of zwitterions and catechol, the hydrogel maintains adhesion in air and underwater environments. In addition, a strain sensor was prepared based on the PSBMA/TA@MMT hydrogel, which can closely fit the human skin and stably monitor different movements in air and in underwater environments. Through a Bluetooth communication system, long-distance information transmission can be achieved. Therefore, the PSBMA/TA@MMT hydrogel broadens the application prospect of wearable devices in the underwater environment.

Hospitalization, case fatality, comorbidities, and isolated pathogens of adult inpatients with pneumonia from 2013 to 2022: a real-world study in Guangzhou, China.

BACKGROUND: In the context of increasing population aging, ongoing drug-resistant pathogens and the COVID-19 epidemic, the changes in the epidemiological and clinical characteristics of patients with pneumonia remain unclear. This study aimed to assess the trends in hospitalization, case fatality, comorbidities, and isolated pathogens of pneumonia-related adult inpatients in Guangzhou during the last decade. METHODS: We retrospectively enrolled hospitalized adults who had doctor-diagnosed pneumonia in the First Affiliated Hospital of Guangzhou Medical University from January 1, 2013 to December 31, 2022. A natural language processing system was applied to automatically extract the clinical data from electronic health records. We evaluated the proportion of pneumonia-related hospitalizations in total hospitalizations, pneumonia-related in-hospital case fatality, comorbidities, and species of isolated pathogens during the last decade. Binary logistic regression analysis was used to assess predictors for patients with prolonged length of stay (LOS). RESULTS: A total of 38,870 cases were finally included in this study, with 70% males, median age of 64 (53, 73) years and median LOS of 7.9 (5.1, 12.8) days. Although the number of pneumonia-related hospitalizations showed an upward trend, the proportion of pneumonia-related hospitalizations decreased from 199.6 per 1000 inpatients in 2013 to 123.4 per 1000 in 2021, and the case fatality decreased from 50.2 per 1000 in 2013 to 23.9 per 1000 in 2022 (all P < 0.05). The most common comorbidities were chronic obstructive pulmonary disease, lung malignancy, cardiovascular diseases and diabetes. The most common pathogens were Pseudomonas aeruginosa, Candida albicans, Acinetobacter baumannii, Stenotrophomonas maltophilia, Klebsiella pneumoniae, and Staphylococcus aureus. Glucocorticoid use during hospitalization (Odd Ratio [OR] = 1.86, 95% Confidence Interval (CI): 1.14-3.06), immunosuppressant use during hospitalization (OR = 1.99, 1.14-3.46), ICU admission (OR = 16.23, 95%CI: 11.25-23.83), receiving mechanical ventilation (OR = 3.58, 95%CI: 2.60-4.97), presence of other underlying diseases (OR = 1.54, 95%CI: 1.15-2.06), and elevated procalcitonin (OR = 1.61, 95%CI: 1.19-2.19) were identified as independent predictors for prolonged LOS. CONCLUSION: The proportion of pneumonia-related hospitalizations and the in-hospital case fatality showed downward trends during the last decade. Pneumonia inpatients were often complicated by chronic underlying diseases and isolated with gram-negative bacteria. ICU admission was a significant predictor for prolonged LOS in pneumonia inpatients.

Diagnostic Value of High-Resolution Vessel Wall Imaging Technique in Intracranial Arterial Stenosis and Occlusion: A Comparative Analysis with Digital Subtraction Angiography.

Objective: To analyze the diagnostic value of HR-VWI in intracranial arterial stenosis and occlusion and compare it with DSA. Methods: A retrospective analysis of clinical data of 59 patients with intracranial arterial stenosis in our hospital was conducted to compare the diagnostic results of the two methods for different degrees of intracranial stenosis and various morphological plaques. Results: The diagnosis of stenosis and occlusion by both methods showed no significant difference (P > 0.05). Comparison of plaque morphology detected by HR-VWI with pathological examination results showed no significant difference (P > 0.05); however, there was a significant difference between plaque morphology detected by DSA and pathological examination results (P < 0.05). Additionally, there was a significant difference between plaque morphology detected by HR-VWI and DSA (P < 0.05). Conclusion: HR-VWI technique is comparable to DSA technique in diagnosing intracranial arterial stenosis and occlusion, but it is superior to DSA in plaque morphology diagnosis.

[Specific changes in gut microbiota and short-chain fatty acid levels in infants with cow's milk protein allergy]. / ç‰›å¥¶è›‹ç™½è¿‡æ•å©´å„¿è‚ é“èŒç¾¤ç‰¹å¼‚æ€§å˜åŒ–åŠçŸ­é“¾è„‚è‚ªé ¸æ°´å¹³åˆ†æž.

OBJECTIVES: To explore the changes in gut microbiota and levels of short-chain fatty acids (SCFA) in infants with cow's milk protein allergy (CMPA), and to clarify their role in CMPA. METHODS: A total of 25 infants diagnosed with CMPA at Children's Hospital Affiliated to Zhengzhou University from August 2019 to August 2020 were enrolled as the CMPA group, and 25 healthy infants were selected as the control group. Fecal samples (200 mg) were collected from both groups and subjected to 16S rDNA high-throughput sequencing technology and liquid chromatography-mass spectrometry to analyze the changes in gut microbial composition and metabolites. Microbial diversity was analyzed in conjunction with metabolites. RESULTS: Compared to the control group, the CMPA group showed altered gut microbial structure and significantly increased α-diversity (P<0.001). The abundance of Firmicutes, Clostridiales and Bacteroidetes was significantly decreased, while the abundance of Sphingomonadaceae, Clostridiaceae_1 and Mycoplasmataceae was significantly increased in the CMPA group compared to the control group (P<0.001). Metabolomic analysis revealed reduced levels of acetic acid, butyric acid, and isovaleric acid in the CMPA group compared to the control group, and the levels of the metabolites were positively correlated with the abundance of SCFA-producing bacteria such as Faecalibacterium and Roseburia (P<0.05). CONCLUSIONS: CMPA infants have alterations in gut microbial structure, increased microbial diversity, and decreased levels of SCFA, which may contribute to increased intestinal inflammation.

Diversity and biogeography of plant phyllosphere bacteria are governed by latitude-dependent mechanisms.

Predicting and managing the structure and function of plant microbiomes requires quantitative understanding of community assembly and predictive models of spatial distributions at broad geographic scales. Here, we quantified the relative contribution of abiotic and biotic factors to the assembly of phyllosphere bacterial communities, and developed spatial distribution models for keystone bacterial taxa along a latitudinal gradient, by analyzing 16S rRNA gene sequences from 1453 leaf samples taken from 329 plant species in China. We demonstrated a latitudinal gradient in phyllosphere bacterial diversity and community composition, which was mostly explained by climate and host plant factors. We found that host-related factors were increasingly important in explaining bacterial assembly at higher latitudes while nonhost factors including abiotic environments, spatial proximity and plant neighbors were more important at lower latitudes. We further showed that local plant-bacteria associations were interconnected by hub bacteria taxa to form metacommunity-level networks, and the spatial distribution of these hub taxa was controlled by hosts and spatial factors with varying importance across latitudes. For the first time, we documented a latitude-dependent importance in the driving factors of phyllosphere bacteria assembly and distribution, serving as a baseline for predicting future changes in plant phyllosphere microbiomes under global change and human activities.

Large-scale fabrication of an ultrathin broadband absorber using quasi-random dielectric Mie resonators.

Ultrathin broadband absorber maintaining a near-uniform low reflectivity over a broadband wavelength is essential for many optical applications, such as light harvesting and nanoscale imaging. Recently, there has been considerable interest in employing arrays of high-index dielectric Mie resonators on surfaces to trap light and reduce the reflectivity. For such Mie-resonant metasurfaces, however, antireflection properties featuring both a flat low reflectance curve and a wide bandwidth are hard to be satisfied simultaneously, and an efficient large-scale nanofabrication technique rarely exists. Here, we present a high-throughput laser interference induced quasi-random patterning (LIIQP) technique to fabricate quasi-random Mie resonators in large scale. Mie resonators with feature sizes down to sub-100 nm have been fabricated using a 1064 nm laser source. Each Mie resonator concentrates light at its shape-dependent resonant frequency, and all such resonators are arranged quasi-randomly to provide both rich (with broadband Fourier components) and strong (with large intensities) Fourier spectra. Specifically, a near-uniform broadband reflectivity over 400-1100 nm spectrum region has been confined below 3% by fabricating a large-scale ultrathin (around 400 nm) absorber. Our concept and high-throughput fabrication technique allows the rapid production of quasi-random dielectric Mie-resonant metasurfaces in a controllable way, which can be used in various promising applications including thin-film solar cells, display, and imaging.

Impairment of intestinal barrier associated with the alternation of intestinal flora and its metabolites in cow's milk protein allergy.

Cow's milk protein allergy (CMPA), one of the most prevalent food allergies, seriously affects the growth and development of infants and children with the rising incidence and prevalence. The dysbiosis of intestinal flora acts to promote disease including allergic disease. Therefore, studying the role of intestinal flora in allergic diseases holds great promise for developing effective strategies to mitigate the risk of food allergies. This study aims to elucidate the role of disrupted intestinal flora and its metabolites in children with CMPA.16S rDNA sequence analysis was applied to characterize the changes in the composition of intestinal flora. The findings revealed heightened diversity of intestinal flora in CMPA, marked by decreased abundance of Firmicutes and Bacteroidetes, and increased abundance of Proteobacteria and Actinobacteria. Furthermore, metabolite analysis identified a total of 1245 differential metabolites in children with CMPA compared to those in healthy children. Among these, 765 metabolites were down-regulated, while 480 were up-regulated. Notably, there were 10 negative differential metabolites identified as bile acids and derivatives, including second bile acids, such as deoxycholic acid, ursodeoxycholic acid and isoursodexycholic acid. The intestinal barrier was further analyzed and showed that the enterocytes proliferation and the expression of Claudin-1, Claudin-3 and MUC2 were down-regulated with the invasion of biofilm community members in the CMPA group. In summary, these findings provide compelling evidence that food allergies disrupt intestinal flora and its metabolites, consequently damaging the intestinal barrier's integrity to increase intestinal permeability and immune response.

Regulation of Hepatocytes in G0 and G1 Phases by NOTCH3 mRNA, miR-369-3p, and rno-Rmdn2_0006 during the Initial Stage of Rat Liver Regeneration.

The key event of liver regeneration initiation (LRI) is the switch of hepatocytes from the G0 phase to the G1 phase. This study aimed to use the data from large-scale quantitatively detecting and analyzing (LQDA) to reveal the regulation of hepatocytes in the G0 or G1 phase by competing endogenous RNAs (ceRNAs) during LRI. The hepatocytes of the rat liver right lobe were isolated 0, 6, and 24 h after partial hepatectomy. Their ceRNA expression level was measured using LQDA, and the correlation among their expression, interaction, and role was revealed by ceRNA comprehensive analysis. The expression of neurogenic loci notch homologous protein 3 (NOTCH3) mRNA was upregulated in 0 h, but the expression of miR-369-3p and rno-Rmdn2_0006 of hepatocytes did not change significantly. Meanwhile, the expression of the G0 phase-related gene CDKN1c was promoted by NOTCH3 upregulation, and the expression of the G1 phase-related gene PSEN2 was inhibited by NOTCH3 downregulation. On the contrary, the expression of NOTCH3 mRNA and rno-Rmdn2_0006 was upregulated at 6 h, but the expression of miR-136-3p was downregulated. The expression of the G1 phase-related genes CHUK, DDX24, HES1, NET1, and STAT3 was promoted by NOTCH3 upregulation, and the expression of the G0 phase-related gene CDKN1a was inhibited by NOTCH3 downregulation. These results suggested that the ceRNAs and the NOTCH3-regulated G0 phase- and G1 phase-related genes showed a correlation in expression, interaction, and role. They together regulated the hepatocytes in the G0 phase at 0 h and in the G1 phase at 6 h. These findings might help understand the mechanism by which ceRNA together regulated the hepatocytes in the G0 or G1 phase.

Employing Visible Light To Construct Photoinitiated Polymerized Nanofiltration Membranes for High Permeation and Environmental Micropollutant Removal.

Improving the nanofiltration (NF) performance of membrane-based treatment is conducive to promoting environmental water recycling and addressing water resource depletion. Combinations of light, electricity, and heat with traditional techniques of preparing membranes should optimize membrane performance. Interfacial polymerization and photopolymerization were integrated to construct a photopolymerized thin-film composite NF membrane with a ridged surface morphology. Under visible light initiation, 2-acrylamido-2-methyl-1-propanesulfonic acid was crosslinked with the polyamide network. The control effects of light on the membrane surface and physicochemical properties were revealed via infrared thermal images and response surface methodology. To present the diffusion motion of piperazine molecules, molecular dynamics simulations were implemented. Through density functional theory simulations, the crosslinking mechanism of the photoinduced NF network was identified and verified. The surface physicochemical characteristics and perm-selectivity performance were systematically illustrated. The photopolymerized membrane outperformed the pristine in permeability and selective separation competence; without degradation of solute repulsion, the water permeation was enhanced to 33.5 L m-2 h-1 bar-1, 6.6 times that of the initial membrane. In addition, the removal of organic contaminants and antifouling capacities were improved. This work represents a novel lead for applying sustainable resources in constructing high-performance membranes for environmental challenges.

The association between small airway dysfunction and aging: a cross-sectional analysis from the ECOPD cohort.

BACKGROUND: Aging has been evidenced to bring about some structural and functional lung changes, especially in COPD. However, whether aging affects SAD, a possible precursor of COPD, has not been well characterized. OBJECTIVE: We aimed to comprehensively assess the relationship between aging and SAD from computed tomography, impulse oscillometry, and spirometry perspectives in Chinese. METHODS: We included 1859 participants from ECOPD, and used a linear-by-linear association test for evaluating the prevalence of SAD across various age subgroups, and multivariate regression models for determining the impact of age on the risk and severity of SAD. We then repeated the analyses in these subjects stratified by airflow limitation. RESULTS: The prevalence of SAD increases over aging regardless of definitional methods. After adjustment for other confounding factors, per 10-yrs increase in age was significantly associated with the risk of CT-defined SAD (OR 2.57, 95% CI 2.13 to 3.10) and the increase in the severity of air trapping (ß 2.09, 95% CI - 0.06 to 4.25 for LAA-856), airway reactance (ß - 0.02, 95% CI - 0.04 to - 0.01 for X5; ß 0.30, 95% CI 0.13 to 0.47 for AX; ß 1.75, 95% CI 0.85 to 2.66 for Fres), as well as the decrease in expiratory flow rates (ß - 3.95, 95% CI - 6.19 to - 1.71 for MMEF%predicted; ß - 5.42, 95% CI - 7.88 to - 2.95 for FEF50%predicted) for SAD. All these associations were generally maintained in SAD defined by IOS or spirometry. After stratification of airflow limitation, we further found that the effect of age on LAA-856 was the most significant among almost all subgroups. CONCLUSIONS: Aging is significantly associated with the prevalence, increased risk, as well as worse severity of SAD. CT may be a more optimal measure to assess aging-related SAD. The molecular mechanisms for the role of aging in SAD need to be explored in the future. Trial registration Chinese Clinical Trial Registry ChiCTR1900024643. Registered on 19 July 2019.

Preserved ratio impaired spirometry is associated with small airway dysfunction and reduced total lung capacity.

BACKGROUND: Preserved ratio impaired spirometry (PRISm) refers to decreased forced expiratory volume in 1 s (FEV1) in the setting of preserved ratio. Little is known about the role of PRISm and its complex relation with small airway dysfunction (SAD) and lung volume. Therefore, we aimed to investigate the associations between PRISm and SAD and lung volume. METHODS: We conducted a cross-sectional community-dwelling study in China. Demographic data, standard respiratory epidemiology questionnaire, spirometry, impulse oscillometry (IOS) and computed tomography (CT) data were collected. PRISm was defined as post-bronchodilator FEV1/FVC ≥ 0.70 and FEV1 < 80% predicted. Spirometry-defined SAD was defined as at least two of three of the post-bronchodilator maximal mid-expiratory flow (MMEF), forced expiratory flow 50% (FEF50), and forced expiratory flow 75% (FEF75) less than 65% of predicted. IOS-defined SAD and CT-defined gas trapping were defined by the fact that the cutoff value of peripheral airway resistance R5-R20 > 0.07 kPa/L/s and LAA- 856>20%, respectively. Analysis of covariance and logistic regression were used to determine associations between PRISm and SAD and lung volume. We then repeated the analysis with a lower limit of normal definition of spirometry criteria and FVC definition of PRISm. Moreover, we also performed subgroup analyses in ever smoker, never smoker, subjects without airway reversibility or self-reported diagnosed asthma, and subjects with CT-measured total lung capacity ≥70% of predicted. RESULTS: The final analysis included 1439 subjects. PRISm had higher odds and more severity in spirometry-defined SAD (pre-bronchodilator: odds ratio [OR]: 5.99, 95% confidence interval [95%CI]: 3.87-9.27, P < 0.001; post-bronchodilator: OR: 14.05, 95%CI: 8.88-22.24, P < 0.001), IOS-defined SAD (OR: 2.89, 95%CI: 1.82-4.58, P < 0.001), and CT-air trapping (OR: 2.01, 95%CI: 1.08-3.72, P = 0.027) compared with healthy control after adjustment for confounding factors. CT-measured total lung capacity in PRISm was lower than that in healthy controls (4.15 ± 0.98 vs. 4.78 ± 1.05 L, P < 0.05), after adjustment. These results were robust in repeating analyses and subgroup analyses. CONCLUSION: Our finding revealed that PRISm was associated with SAD and reduced total lung capacity. Future studies to identify the underlying mechanisms and longitudinal progression of PRISm are warranted.

Metal ion chelation enhances tissue plasminogen activator (tPA)-induced thrombolysis: an in vitro and in vivo study.

Stroke is the third leading cause of death in the United States and the leading cause of adult disability. Despite enormous research efforts including many clinical trials, tissue plasminogen activator (tPA) remains the only FDA-approved treatment for acute ischemic stroke. Unfortunately, only 1-3% of stroke patients in the US receive this therapy because of the narrow time window and severe side effects for using tPA. The most deadly and damaging side effect is the risk of intracranial bleeding or hemorrhage. For that reason, the dose of tPA and its overall administration are under tight control, which may compromise the effect of thrombolysis. Studies have been focused on improving the effectiveness of tPA for higher rate of reperfusion, and the safety for less adverse bleeding episode. We studied how metal ions (zinc & iron) affect tPA-induced thrombolysis in vitro and in vivo, and proposed a method to improve the rate of thrombolysis. The amount of hemoglobin in the blood clot lysis was measured by a spectrophotometer. The tPA-induced thrombolysis was measured in vivo in femoral artery. Our results showed that Zn2+, Fe3+ and Fe2+ inhibited tPA-induced thrombolysis, with Zn2+ and Fe2+ being the most effective. Metal ion chelating agent EDTA when it was co-applied with tPA significantly enhanced the tPA-induced thrombolysis. The chelation alone did not have noticeable thrombolytic effect. In in vivo study of tPA-induced thrombosis following femoral artery thrombosis, the co-application of tPA and EDTA achieved significant higher rate of reperfusion than that by tPA treatment alone, suggesting that ion chelation facilitates tPA-induced thrombolysis and potentially improves the safety of tPA application by reducing the necessary dose of tPA application. Our results suggest that the co-application of a chelator and tPA improves the efficacy and, potentially, safety of tPA application, by reducing the necessary dose of tPA for thrombolysis.

Validity of a portable spirometer in the communities of China.

BACKGROUND: The lack of simple and affordable spirometry has led to the missed and delayed diagnoses of chronic respiratory diseases in communities. The PUS201P is a portable spirometry developed to solve this problem. OBJECTIVE: We aimed to verify the consistency of the PUS201P spirometer with conventional Jaeger spirometer. METHODS: In this cross-sectional study, we randomly recruited 202 subjects aged > 40 years. Testing with the portable spirometry and conventional spirometry were performed on all participants. We compared forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC measured by the PUS201P device with the conventional spirometer. Pearson correlation coefficient and Interclass Correlation Coefficient (ICC) were assessed to confirm the consistency of the measures from two instruments. Bland-Altman graph was created to assess the agreement of the measures from two devices. RESULTS: 202 participants were included in this study. The ICC on FEV1, FVC, FEV1/FVC measured by the portable spirometer and the conventional spirometer were 0.95 (95% confidence interval [CI]: 0.94-0.96), 0.92 (95% CI: 0.90-0.94], 0.93 (95% CI: 0.91-0.95), respectively. The Bland-Altman plots showed that the mean difference between the measures from two spirometers are always located in the 95% limits of agreement. CONCLUSIONS: Our results support that the measures from the portable spirometer and the conventional spirometer have a good agreement and reproducibility. And the portable spirometer is a reliable tool to screen and diagnose chronic airway diseases in the primary care settings.

Heat stress and hypoxia inhibit the secretion of androgens and induce epithelial-to-mesenchymal transition associated with activated TGF-ß/Smad signalling in canine cryptorchidism.

Cryptorchidism, as a common congenital disease of canine testes, is mainly caused by factors leading to endocrine abnormalities in testes and infertility in a heat stress and hypoxia microenvironment. Moreover, heat stress and hypoxia, as critical microenvironmental factors, promote epithelial-mesenchymal transition (EMT), which occurs during adult tissue remodelling responses including carcinogenesis and fibrosis and is the main cause of testicular tumours. In this study, we found by haematoxylin-eosin staining that the canine cryptorchid tissue produced a lot of collagen fibres. Also, the quantitative PCR and Western blot results showed that the mRNA and protein levels of the heat stress makers HSP70 and HO-1 and the hypoxia maker HIF-1α are significant higher compared with normal testes. Moreover, we found the expression levels of TGF-ßs and its two receptors TGF-ßRI and TGF-ßRII increased in case of cryptorchidism. From the study in vitro, we found both heat stress and COCl2 mimic hypoxia inhibited the secretion of testosterone (T) and androstenedione (A4) and promoted the expression of the EMT maker α-SMA and vimentin in Leydig cells, and also that heat stress and COCl2 stimulated with the TGF-ß signalling promoted the expression of TGF-ßs and its two type receptors and also the active phosphorylation of Smad2 and Smad3. The use of LY2109761, a receptor inhibitor of TGF-ßs/Smad signalling pathway, was associated with heat stress and COCl2 suppression of androgens' secretion and stimulated EMT in Leydig cells. These findings characterized a novel pathogenesis of cryptorchidism and provided a new idea for therapeutics.

Overexpression of a Plasma Membrane H+-ATPase Gene OSA1 Stimulates the Uptake of Primary Macronutrients in Rice Roots.

Plasma membrane (PM) H+-ATPase is a master enzyme involved in various plant physiological processes, such as stomatal movements in leaves and nutrient uptake and transport in roots. Overexpression of Oryza sativa PM H+-ATPase 1 (OSA1) has been known to increase NH4+ uptake in rice roots. Although electrophysiological and pharmacological experiments have shown that the transport of many substances is dependent on the proton motive force provided by PM H+-ATPase, the exact role of PM H+-ATPase on the uptake of nutrients in plant roots, especially for the primary macronutrients N, P, and K, is still largely unknown. Here, we used OSA1 overexpression lines (OSA1-oxs) and gene-knockout osa1 mutants to investigate the effect of modulation of PM H+-ATPase on the absorption of N, P, and K nutrients through the use of a nutrient-exhaustive method and noninvasive microtest technology (NMT) in rice roots. Our results showed that under different concentrations of P and K, the uptake rates of P and K were enhanced in OSA1-oxs; by contrast, the uptake rates of P and K were significantly reduced in roots of osa1 mutants when compared with wild-type. In addition, the net influx rates of NH4+ and K+, as well as the efflux rate of H+, were enhanced in OSA1-oxs and suppressed in osa1 mutants under low concentration conditions. In summary, this study indicated that overexpression of OSA1 stimulated the uptake rate of N, P, and K and promoted flux rates of cations (i.e., H+, NH4+, and K+) in rice roots. These results may provide a novel insight into improving the coordinated utilization of macronutrients in crop plants.

The OsCBL8-OsCIPK17 Module Regulates Seedling Growth and Confers Resistance to Heat and Drought in Rice.

The calcium signaling pathway is critical for plant growth, development, and response to external stimuli. The CBL-CIPK pathway has been well characterized as a calcium-signaling pathway. However, in most reports, only a single function for this module has been described. Here, we examined multiple functions of this module. CIPK showed a similar distribution to that of CBL, and OsCBL and OsCIPK families were retained after experiencing whole genome duplication events through the phylogenetic and synteny analysis. This study found that OsCBL8 negatively regulated rice seed germination and seedling growth by interacting with OsCIPK17 with overexpression and gene editing mutant plants as materials combining plant phenotype, physiological indicators and transcriptome sequencing. This process is likely mediated by OsPP2C77, which is a member of the ABA signaling pathway. In addition, OsCBL mediated the targeting of OsNAC77 and OsJAMYB by OsCIPK17, thus conferring resistance to high temperatures and pathogens in rice. Our work reveals a unique signaling pathway, wherein OsCBL8 interacts with OsCIPK17 and provides rice with multiple resistance while also regulating seedling growth.

miR-128 regulates epilepsy sensitivity in mice by suppressing SNAP-25 and SYT1 expression in the hippocampus.

Epilepsy is accompanied by abnormal neurotransmission, and microRNAs, as versatile players in the modulation of gene expression, are important in epilepsy pathology. Here, we found that miR-128 expression was elevated in the acute seizure phase and decreased during the recurrent seizure phase after status epilepticus in mice. Both SNAP-25 and SYT1 are regulated by miR-128 in vitro and in vivo. Overexpressing miR-128 in cultured neurons decreased neurotransmitter released by suppressing SNAP-25 and SYT1 expression. Anti-miR-128 injection before kainic acid (KA) injection increased the sensitivity of mice to KA-induced seizures, while overexpressing miR-128 at the latent and recurrent phases had a neuroprotective effect in KA-induced seizures. Our study shows for the first time that miR-128, a key regulator of neurotransmission, plays an important role in epilepsy pathology and that miR-128 might be a potential candidate molecular target for epilepsy therapy.

Nanofiltration Membranes with Octopus Arm-Sucker Surface Morphology: Filtration Performance and Mechanism Investigation.

Precisely tailoring the surface morphology characteristics of the active layers based on bionic inspirations can improve the performance of thin-film composite (TFC) membranes. The remarkable water adsorption and capture abilities of octopus tentacles inspired the construction of a novel TFC nanofiltration (NF) membrane with octopus arm-sucker morphology using carbon nanotubes (CNTs) and beta-cyclodextrin (ß-CD) during interfacial polymerization (IP). The surface morphology, chemical elements, water contact angle (WCA), interfacial free energy (ΔG), electronegativity, and pore size of the membranes were systematically investigated. The optimal membrane exhibited an enhanced water permeance of 22.6 L·m-2·h-1·bar-1, 180% better than that of the TFC-control membrane. In addition, the optimal membrane showed improved single salt rejections and monovalent/divalent ion selectivity and can break the trade-off effect. The antiscaling performance and stability of the membranes were further explored. The construction mechanism of the octopus arm-sucker structure was excavated, in which CNTs and ß-CD acted as arm skeletons and suckers, respectively. Furthermore, the customization of the membrane surface and performance was achieved through tuning the individual effects of the arm skeletons and suckers. This study highlights the noteworthy potential of the design and construction of the surface morphology of high-performance NF membranes for environmental application.