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Abstract Researchers have typically studied the brain by monitoring characteristic signals, such as electrophysiology and neurotransmitters by implanted electronics. Here, real‐time monitoring of dynamic deformations of the brain tissue in vivo, is demonstrated, as a new characteristic parameter that is reflective of brain states. As a proof of concept, a thin capacitive deformation sensor is fabricated and implanted between the skull and cortex, and the sensor is shown to effectively monitor dynamic deformations of the cortical surface in the rat brain as induced by respiration and heartbeat under different degrees of anesthesia. This brain monitoring approach based on deformation signals opens up a new direction for understanding the brain.

Abstract Objective Efficacy and safety of perampanel monotherapy for treating focal‐onset seizures (FOS) has been barely studied in China. This observational study aimed to evaluate the efficacy and safety of perampanel monotherapy in treating Chinese patients with FOS. Methods This single‐center, prospective, real‐world observational study enrolled patients aged ≥4 years with FOS who visited the Epilepsy Out‐Patient Clinic of Nanjing Brain Hospital affiliated to Nanjing Medical University from January 2020 to December 2021. All patients were treated with perampanel monotherapy. Seizure‐freedom rates after 6 and 12 months of treatment were calculated. Adverse events (AEs) were recorded. Results Seventy patients with FOS were enrolled. The mean maintenance perampanel dose was 4.64 ± 1.55 mg/day. The 6‐ and 12‐month retention rates of perampanel monotherapy were 78.6% (55/70) and 70.0% (49/70), respectively. The 6‐ and 12‐month seizure‐freedom rates were 69.84% (44/63) and 65.08% (41/63), respectively. Patients with focal to bilateral tonic–clonic seizures had significantly higher 6‐month and numerically higher 12‐month seizure freedom rates than patients with focal impaired awareness seizures (P = 0.046 and P = 0.204, respectively). Twenty‐six (37.1%) patients experienced treatment‐emergent AEs, and the most common AE was dizziness. Four (5.7%) patients withdrew from the study due to AEs. No new safety concern was observed. Significance This is the first prospective study on the efficacy and safety of perampanel monotherapy in treating Chinese patients with FOS, and perampanel monotherapy was effective and safe in treating Chinese patients aged ≥4 years with FOS up to 12 months. More multicenter, real‐world studies with large sample sizes and longer follow‐ups are needed to further evaluate the long‐term efficacy and safety of perampanel monotherapy.

Abstract Metabolic reprogramming and epigenetic modifications are hallmarks of cancer cells. In cancer cells, metabolic pathway activity varies during tumorigenesis and cancer progression, indicating regulated metabolic plasticity. Metabolic changes are often closely related to epigenetic changes, such as alterations in the expression or activity of epigenetically modified enzymes, which may exert a direct or an indirect influence on cellular metabolism. Therefore, exploring the mechanisms underlying epigenetic modifications regulating the reprogramming of tumor cell metabolism is important for further understanding tumor pathogenesis. Here, we mainly focus on the latest studies on epigenetic modifications related to cancer cell metabolism regulations, including changes in glucose, lipid and amino acid metabolism in the cancer context, and then emphasize the mechanisms related to tumor cell epigenetic modifications. Specifically, we discuss the role played by DNA methylation, chromatin remodeling, noncoding RNAs and histone lactylation in tumor growth and progression. Finally, we summarize the prospects of potential cancer therapeutic strategies based on metabolic reprogramming and epigenetic changes in tumor cells.

Based on the typical dissection of various onshore tight oil fields in China, the tight oil migration and accumulation mechanism and enrichment-controlling factors in continental lake basins are analyzed through nuclear magnetic resonance (NMR) displacement physical simulation and Lattice Boltzmann numerical simulation by using the samples of source rock, reservoir rock and crude oil. In continental lake basins, the dynamic forces driving hydrocarbon generation and expulsion of high-quality source rocks are the foundational power that determines the charging efficiency and accumulation effect of tight oil, the oil migration resistance is a key element that influences the charging efficiency and accumulation effect of tight oil, and the coupling of charging force with pore-throat resistance in tight reservoir controls the tight oil accumulation and sweet spot enrichment. The degree of tight oil enrichment in continental lake basins is controlled by four factors: source rock, reservoir pore-throat size, anisotropy of reservoir structure, and fractures. The high-quality source rocks control the near-source distribution of tight oil, reservoir physical properties and pore-throat size are positively correlated with the degree of tight oil enrichment, the anisotropy of reservoir structure reveals that the parallel migration rate is the highest, and intralayer fractures can improve the migration and accumulation efficiency and the oil saturation.

BackgroundRates of overweight and obesity continue to grow in adolescents. Overweight and obesity in adolescence are associated with numerous immediate and long-term adverse health conditions. Throughout adolescence, parents and the family have an important and central influence on adolescents' health and lifestyle. The home environment may be a major factor in shaping children's weight. However, our current understanding of the interplay between family-related variables in adolescents with overweight or obesity is limited and fragmented. This study aimed to assess the relationship between family-related variables in adolescents who are overweight or obese using network analysis and inform future health promotion for family-based intervention.MethodsParticipants (n = 488) were recruited from middle schools in Nanjing from October 2022 to March 2023. Participants, together with their parents, completed a questionnaire at school about the family food environment, family size, family APGAR index, family physical activity facilities, parental mental health, rearing behavior, parental weight status, drinking history, marital satisfaction, and sociodemographic characteristics.ResultsThe network split into three distinct communities of items. Network analysis showed that parental mental health and paternal rearing styles-rejection were the most central nodes in the network. In contrast, maternal weight status was the most peripheral and least connected nodes.ConclusionFamily-related variables constituted a connected network in adolescents with overweight or obesity. The pattern of network node connections supports that interventions could prioritize targeting changing parental mental health and paternal rearing styles in adolescents with overweight or obesity.

Abstract Metabolic reprogramming is one of the hallmarks of cancer. As nutrients are scarce in the tumor microenvironment (TME), tumor cells adopt multiple metabolic adaptations to meet their growth requirements. Metabolic reprogramming is not only present in tumor cells, but exosomal cargos mediates intercellular communication between tumor cells and non-tumor cells in the TME, inducing metabolic remodeling to create an outpost of microvascular enrichment and immune escape. Here, we highlight the composition and characteristics of TME, meanwhile summarize the components of exosomal cargos and their corresponding sorting mode. Functionally, these exosomal cargos-mediated metabolic reprogramming improves the "soil" for tumor growth and metastasis. Moreover, we discuss the abnormal tumor metabolism targeted by exosomal cargos and its potential antitumor therapy. In conclusion, this review updates the current role of exosomal cargos in TME metabolic reprogramming and enriches the future application scenarios of exosomes.

Abstract Prohibitins (PHBs) are a class of highly evolutionarily conserved proteins that widely distribute in prokaryotes and eukaryotes. PHBs function in cell growth and proliferation or differentiation, regulating metabolism and signaling pathways. PHBs have different subcellular localization in eukaryotes, but they are mainly located in mitochondria. In the mitochondria, PHBs stabilize the structure of the mitochondrial membrane and regulate mitochondrial autophagy, mitochondrial dynamics, mitochondrial biogenesis and quality control, and mitochondrial unfolded protein response. PHBs has shown to be associated with many diseases, such as mitochondria diseases, cancers, infectious diseases, and so on. Some molecule targets of PHBs can interfere with the occurrence and development of diseases. Therefore, this review clarifies the functions of PHBs in mitochondria, and provides a summary of the potential values in clinics.

Abstracts Pathological cardiac hypertrophy is a key contributor in heart failure (HF). Long non-coding RNAs (lncRNAs) and N6-methyladenosine (m6A) modification play a vital role in cardiac hypertrophy respectively. Nevertheless, the interaction between lncRNA and m6A methylase in cardiac hypertrophy is scarcely reported. Here, we constructed a cardiac hypertrophy mouse model by transverse aortic constriction (TAC) surgery and H9c2 cell model by stimulating with AngII. We found that lncRNA MIAT mRNA level, and m6A RNA methylation reading protein Ythdf2 mRNA and protein levels, were significantly increased in the cardiac hypertrophy model both in vivo and vitro. MIAT or Ythdf2 overexpression aggravated cardiac hypertrophy, and vice versa. Through bioinformatics prediction, western blotting, FISH, RNA pull-down, and RIP, we found that MIAT bound to Ythdf2 and regulated its expression. Furthermore, we discovered that Ythdf2 function was a downstream of MIAT in cardiac hypertrophy. Finally, we found that MIAT was a necessary regulator of cardiac hypertrophy due to its regulation of the Ythdf2/PPARα/CPT-1a axis. This study indicated a new hypertrophic signaling pathway: MIAT/Ythdf2/PPARα/CPT-1a. The results provided a new understanding of the MIAT and m6A RNA methylation reading protein, Ythdf2, function and mechanism in cardiac hypertrophy and highlighted the potential therapeutic benefits in the heart.

Tripartite motif-containing 28 (TRIM28) belongs to tripartite motif (TRIM) family. TRIM28 not only binds and degrades its downstream target, but also acts as a transcription co-factor to inhibit gene expression. More and more studies have shown that TRIM28 plays a vital role in tumor genesis and progression. Here, we reviewed the role of TRIM28 in tumor proliferation, migration, invasion and cell death. Moreover, we also summarized the important role of TRIM28 in tumor stemness sustainability and immune regulation. Because of the importance of TRIM28 in tumors, TIRM28 may be a candidate target for anti-tumor therapy and play an important role in tumor diagnosis and treatment in the future.

The aim of this study was to investigate whether and how exosomal miR-205-5p regulated angiogenesis and nasopharyngeal carcinoma (NPC) metastasis. We found that up-regulated serum exosomal miR-205-5p levels were associated with NPC progression and worse overall survival of NPC patients. miR-205-5p over-expression significantly increased tube formation, wound healing, migration and invasion of NPC cells, and lung metastasis of NPC tumors, whereas miR-205-5p inhibition had opposite effects. Exosomal miR-205-5p from NPC cells promoted the migration, tube formation, and microvessel density (MVD) of HUVECs in vitro and in vivo. Furthermore, bioinformatics-, luciferase reporter-, and biotinylated miR-205-5p-based pull-down assays indicated that miR-205-5p directly bound to the 3′ UTR of desmocollin-2 (DSC2). Exosomal miR-205-5p targeted DSC2 to enhance the EGFR/ERK signaling and MMP2/MMP9 expression, promoting angiogenesis and NPC metastasis, which was abrogated by DSC2 over-expression. Finally, the levels of miR-205-5p transcripts were positively correlated with MVD but negatively with DSC2 expression in NPC tissues, and patients with miR-205high/DSC2low NPC had worse overall survival. In conclusion, exosomal miR-205-5p promotes angiogenesis and NPC metastasis by targeting DSC2 to enhance EGFR/ERK signaling and MMP expression. This exosomal/miR-205-5p/EGFR/ERK axis may be a new therapeutic target for intervention of NPC metastasis.

A piezoelectric vibration sensing system (PVSS) was devised in this study and employed for the purpose of vibration sensing in machining. The system comprises three primary components, wherein the sensor is utilized for the collection and conversion of energy, subsequently transmitting it to the data acquisition card (DAC) via a low-noise cable. The crux of the entire system lies in the upper computer-based control application, which facilitates the transmission of instructions to the DAC for data acquisition and transmission. The integration of Wi-Fi data transfer capability between the DAC and the computer serves to eliminate the principal issue associated with employing the sensor as a voltage source. The sensitivity of the designed device was calibrated utilizing commercial accelerometers, while an aluminum workpiece was fabricated to conduct vibration and machining tests in order to verify the performance of the PVSS. The shaker excitation experiment yielded a peak voltage of 0.05 mV, thereby substantiating that the PVSS can more accurately discern the natural frequency of the workpiece below 5000 Hz compared to commercial accelerometers. The experiments verify that the devised PVSS can precisely measure vibrations during the milling process, and can be implemented for the purpose of detecting machining stability.

Abstract Background Polycystic ovary syndrome (PCOS) is a common endocrine disorder with the disorders of estrogen(E2) and progesterone(P) secretion. The purpose of this study was to evaluate the association between the progesterone level or progesterone/estradiol(P/E2) ratio on human chorionic gonadotropin (hCG) trigger day and the outcome of in vitro fertilization in PCOS patients and explore the value of progesterone and P/E2 ratio for predicting the clinical pregnancy. Methods The clinical data of 1254 PCOS patients who satisfied the inclusion criteria were retrospectively analyzed, including baseline characteristics such as age, body mass index, basal sex hormone levels, et al., as well as ovarian stimulation data and clinic outcome. Results The number of follicles larger than 14 mm in diameter (P

Abstract Background Polycystic ovary syndrome (PCOS) is a disease with chronic nonspecific low-grade inflammation. The imbalance of immune cells exists in PCOS. Several studies have found that heat shock protein 70 (HSP70) may be involved in the immunological pathogenesis of PCOS, but the relationship between HSP70 and Regulatory T cell (Treg)/T helper cell 17(Th17) ratio remains unclear. This study aims to explore the correlation between HSP70 and Treg/Th17 ratio and to provide evidence for the role of HSP70 in the immunological etiology of PCOS. Results There was no significant difference in age and body mass index (BMI) between the two groups. The concentrations of basal estradiol (E2), basal follicle-stimulating hormone (FSH) did not show a significant difference between the two groups. The concentrations of basal luteinizing hormone (LH) (P

Malaria still threatens global health seriously today. While the current discoveries of antimalarials are almost totally focused on single mode-of-action inhibitors, multi-targeting inhibitors are highly desired to overcome the increasingly serious drug resistance. Here, we performed a structure-based drug design on mitochondrial respiratory chain of Plasmodium falciparum and identified an extremely potent molecule, RYL-581, which binds to multiple protein binding sites of P. falciparum simultaneously (allosteric site of type II NADH dehydrogenase, Qo and Qi sites of cytochrome bc1). Antimalarials with such multiple targeting mechanism of action have never been reported before. RYL-581 kills various drug-resistant strains in vitro and shows good solubility as well as in vivo activity. This structure-based strategy for designing RYL-581 from starting compound may be helpful for other medicinal chemistry projects in the future, especially for drug discovery on membrane-associated targets.

Abstract Chitosan is an amorphous translucent substance with a structural unit similar to the polysaccharide structure of the extracellular matrix, It has good antibacterial, biocompatible, and degradable properties. It has important application value in leather, water treatment, medicine, food and other fields, so chitosan and its modified products have received widespread attention. This article reviewed the preparation methods of chitosan-based antibacterial composites in recent years, including chitosan/collagen, chitosan/graphene, chitosan/tannic acid, and chitosan/polyethylene glycol composite materials, elaborates their modification methods and antibacterial mechanism were reviewed in detail, and its applications in the leather industry as antibacterial auxiliaries and water treatment antibacterial adsorption materials were discussed. Finally, the future development and challenges of chitosan-based composite materials in the leather industry were forecasted. Graphical abstract

Abstract The overlapping metabolic reprogramming of cancer and immune cells is a putative determinant of the antitumor immune response in cancer. Increased evidence suggests that cancer metabolism not only plays a crucial role in cancer signaling for sustaining tumorigenesis and survival, but also has wider implications in the regulation of antitumor immune response through both the release of metabolites and affecting the expression of immune molecules, such as lactate, PGE2, arginine, etc. Actually, this energetic interplay between tumor and immune cells leads to metabolic competition in the tumor ecosystem, limiting nutrient availability and leading to microenvironmental acidosis, which hinders immune cell function. More interestingly, metabolic reprogramming is also indispensable in the process of maintaining self and body homeostasis by various types of immune cells. At present, more and more studies pointed out that immune cell would undergo metabolic reprogramming during the process of proliferation, differentiation, and execution of effector functions, which is essential to the immune response. Herein, we discuss how metabolic reprogramming of cancer cells and immune cells regulate antitumor immune response and the possible approaches to targeting metabolic pathways in the context of anticancer immunotherapy. We also describe hypothetical combination treatments between immunotherapy and metabolic intervening that could be used to better unleash the potential of anticancer therapies.

Abstract Plastid genomes (plastomes) have a quadripartite structure, but some species have drastically reduced or lost inverted repeat (IR) regions. IR regions are important for genome stability and the evolution rate. In the evolutionary process of gymnosperms, the typical IRs of conifers were lost, possibly affecting the evolutionary rate and selection pressure of genomic protein‐coding genes. In this study, we selected 78 gymnosperm species (51 genera, 13 families) for evolutionary analysis. The selection pressure analysis results showed that negative selection effects were detected in all 50 common genes. Among them, six genes in conifers had higher ω values than non‐conifers, and 12 genes had lower ω values. The evolutionary rate analysis results showed that 9 of 50 common genes differed between conifers and non‐conifers. It is more obvious that in non‐conifers, the rates of psbA (trst, trsv, ratio, dN, dS, and ω) were 2.6‐ to 3.1‐fold of conifers. In conifers, trsv, ratio, dN, dS, and ω of ycf2 were 1.2‐ to 3.6‐fold of non‐conifers. In addition, the evolution rate of ycf2 in the IR was significantly reduced. psbA is undergoing dynamic change, with an abnormally high evolution rate as a small portion of it enters the IR region. Although conifers have lost the typical IR regions, we detected no change in the substitution rate or selection pressure of most protein‐coding genes due to gene function, plant habitat, or newly acquired IRs.

Abstract Background Tea plant (Camellia sinensis) is one of the most popular non-alcoholic beverages worldwide. In tea, lateral roots (LRs) are the main organ responsible for the absorption of moisture and mineral nutrients from the soil. Lateral roots formation and development are regulated by the nitrogen and auxin signaling pathways. In order to understand the role of auxin and nitrogen signaling in LRs formation and development, transcriptome analysis was employed to investigate the differentially expressed genes involved in lateral roots of tea plants treated with indole-3-butyric acid (IBA), N-1-naphthylphthalamic acid (NPA), low and high concentrations of nitrogen. Results A total of 296 common differentially expressed genes were identified and annotated to four signaling pathways, including nitrogen metabolism, plant hormone signal transduction, glutathione metabolism and transcription factors. RNA-sequencing results revealed that majority of differentially expressed genes play important roles in nitrogen metabolism and hormonal signal transduction. Low nitrogen condition induced the biosynthesis of auxin and accumulation of transcripts, thereby, regulating lateral roots formation. Furthermore, metabolism of cytokinin and ethylene biosynthesis were also involved in lateral roots development. Transcription factors like MYB genes also contributed to lateral roots formation of tea plants through secondary cell wall biosynthesis. Reversed phase ultra performance liquid chromatography (RP-UPLC) results showed that the auxin concentration increased with the decreased nitrogen level in lateral roots. Thus, tea plant lateral roots formation could be induced by low nitrogen concentration via auxin biosynthesis and accumulation. Conclusion This study provided insights into the mechanisms associated with nitrogen and auxin signaling pathways in LRs formation and provides information on the efficient utilization of nitrogen in tea plant at the genetic level.

Directly modulated tunable lasers are highly desirable for constructing dense-wavelength division multiplexing (DWDM) access networks, owing to their advantages of low cost, compact size and low power consumption. However, the transmission distance for 10 Gbps is usually limited to about 10 km in the telecom C-band in standard single-mode fiber (SMF) due to wavelength chirp. Here we propose and demonstrate a simple technique for extending the transmission distance by detuning the wavelength of a tunable V-cavity laser with respect to DWDM multiplexers. Experiment results show that 10 Gbps signal can be transmitted error-free (BER-12) over 20 km SMF with a wavelength-detuning with respect to a Gaussian-type arrayed waveguide grating (AWG) without dispersion compensation. The power penalty is only 1 dB compared to the back-to-back transmission.

The aim of the present study was to evaluate the prognostic value of interventricular septum thickness (IVSd) on the incidence of cardiovascular diseases. Based on the general population in Northeast China, 10,349 participants were successfully followed up for echocardiography over a median follow-up time of 4.66 years, among which 4801 were hypertensive. Coronary heart disease (CHD) and myocardial infarction (MI) incidence were followed up. Cox proportional hazards models were used to estimate the association of the baseline IVSd with adverse outcomes. IVS hypertrophy increased incident rates of CHD and MI compared with normal IVSd in the overall population and in the female sex-stratification group. In males, IVS hypertrophy had parallel increase rates of CHD (all p < 0.05). Kaplan–Meier analysis showed that IVS hypertrophy could predict CHD and MI incidence and CHD-free and MI-free survival. Multivariable Cox analysis revealed that IVS hypertrophy was correlated with CHD incidence (HR = 1.155, 95% CI = 1.155–2.861, p = 0.01) and MI incidence (HR = 2.410, 95% CI = 1.303–4.458, p = 0.005). In women, IVS hypertrophy was independently associated with CHD and MI incidence (all p < 0.05). Our prospective cohort study illustrated that IVS hypertrophy detected by echocardiography has a prognostic significance for CHD and MI. Therefore, the early detection of IVSd should be conducted to avoid adverse outcomes in further clinical practice.

The orphan G protein-coupled receptor G2A has been linked to atherosclerosis development. However, available data from mouse models are controversial. Rat G2A receptor bears more similarities with its human homolog. We proposed that the atherosclerosis model established from Ldlr–/– rat, which has been reported to share more similar phenotypes with the human disease, may help to further understand this lipid receptor. G2A deletion was found markedly aggravated in the lipid disorder in the rat model, which has not been reported in mouse studies. Examination of aortas revealed exacerbated atherosclerotic plaques in G2A deficient rats, together with increased oxidative stress and macrophage accumulation. In addition, consistently promoted migration and apoptosis were noticed in G2A deficient macrophages, even in macrophages from G2A single knockout rats. Further analysis found significantly declined phosphorylation of PI3 kinase (PI3K) and AKT, together with reduced downstream genes Bcl2 and Bcl-xl, suggesting possible involvement of PI3K/AKT pathway in G2A regulation to macrophage apoptosis. These data indicate that G2A modulates atherosclerosis by regulating lipid metabolism and macrophage migration and apoptosis. Our study provides a new understanding of the role of G2A in atherosclerosis, supporting it as a potential therapeutic target.

The surface of Bacillus megaterium was modified by coating sodium alginate. The modified B. megaterium before and after adsorption were characterized by SEM, FTIR and XPS. The effects of pH, reaction time, initial U(VI) concentration and adsorbent dosage on the adsorption of U(VI) by the modified B. megaterium were studied by batch adsorption experiments. The adsorption process was studied by pseudo-first-order kinetics and pseudo-second-order kinetic models, Langmuir and Freundlich isotherms. The results showed that the maximum adsorption capacity of U(VI) was 74.61 mg g−1 under the conditions of pH 5.0, adsorbent 0.2 g l−1, 30°C and initial U(VI) concentration of 15 mg l−1. The adsorption process accords with pseudo-first-order kinetics and Langmuir isotherm. The adsorption capacity of U(VI) by the modified B. megaterium was still higher than 80% after five times of desorption and reuse experiments. In conclusion, the sodium alginate modified B. megaterium was an ideal material for U(VI) biosorption.

Planetary gearbox is widely used in various low-speed machines due to its large transmission ratio. However, the gears in a planetary gearbox are prone to the mechanical faults due to the complex dynamic heavy load. Vibration frequencies caused by an early tooth root crack of sun gear are usually difficult to accurately extract, so its fault diagnosis is one of the main challenges of planetary gearbox reliability. In this paper, a simplified tooth root crack model of sun gear is proposed, and then a rigid-flexible coupled dynamics model of the whole planetary gear system is constructed. By the numerical simulation, the fault frequencies caused by a tooth root crack of sun gear are obtained. A Variational Mode Decomposition (VMD) algorithm for the vibration frequency extraction is proposed. The measured vibration signals are decomposed into the sparse Intrinsic Mode Functions (IMFs) by the VMD, and then the IMFs are further analyzed by the spectral method to accurately extract the crack-induced frequency components. The experimental results show that the proposed dynamics model and VMD method are feasible; an error between the characteristic frequencies from the tested signal analysis and the theoretical calculation is less than 1%.

Thaumatin-like proteins (TLPs), which are defined as pathogenesis-related protein family 5 (PR5) members, are common plant proteins involved in defense responses and confer antifungal activity against many plant pathogens. Our earlier studies have reported that the TaTLP1 gene was isolated from wheat and proved to be involved in wheat defense in response to leaf rust attack. The present study aims to identify the interacting proteins of TaTLP1 and characterize the role of the interaction between wheat and Puccinia triticina (Pt). Pull-down experiments designed to isolate the molecular target of TaTLP1 in tobacco resulted in the identification of TaPR1, a pathogenesis-related protein of family 1, and the interaction between TaTLP1 and TaPR1 was confirmed by yeast two-hybrid experiments (Y2H), bimolecular fluorescence complementation (BiFC), and co-immunoprecipitation (Co-IP). In vitro, TaTLP1 and TaPR1 together increased antifungal activity against Pt. In vivo, the disease resistance phenotype, histological observations of fungal growth and host responses, and accumulation of H2O2 in TaTLP1-TaPR1 in co-silenced plants indicated that co-silencing significantly enhanced wheat susceptibility compared to single knockdown TaTLP1 or TaPR1 plants. The accumulation of reactive oxygen species (ROS) was significantly reduced in co-silenced plants compared to controls during Pt infection, which suggested that the TaTLP1-TaPR1 interaction positively modulates wheat resistance to Pt in an ROS-dependent manner. Our findings provide new insights for understanding the roles of two different PRs, TaTLP1 and TaPR1, in wheat resistance to leaf rust.

Antifungal activities of plant-beneficial Bacillus have been widely studied in recent years. Numerous studies have studied the antifungal mechanisms of soluble non-volatile bioactive compounds such as lipopeptides and proteins produced by Bacillus against soil-borne diseases. However, the antagonistic mechanisms of volatile organic compounds (VOCs) from Bacillus against airborne phytopathogens are still largely unknown, and the function of Alternaria solani pathogenic genes has not been well identified. Here, we first isolated a Bacillus strain with strong antifungal activity and finally identified it as B. subtilis ZD01. Then, the antagonistic mechanisms of VOCs produced by strain ZD01, against A. solani, an airborne fungal pathogen that can cause early blight diseases of potato, were studied. We showed that VOCs produced by strain ZD01 can reduce the colony size and mycelial penetration and can cause serious morphological changes of A. solani. Scanning electron microscope (SEM) observation showed that VOCs released by ZD01 could cause more flaccid and gapped hyphae of A. solani. Also, we found that VOCs produced by ZD01 can inhibit the conidia germination and reduce the lesion areas and number of A. solani in vivo significantly. Meanwhile, based on gas chromatography/mass spectrometry (GC/MS) analysis, 29 volatile compounds produced by strain ZD01 were identified. Out of 29 identified VOCs, 9 VOCs showed complete growth inhibition activities against A. solani. Moreover, we identified two virulence-associated genes (slt2 and sod) in A. solani. slt2 is a key gene that regulates the mycelial growth, penetration, sporulation, and virulence in vivo in A. solani. In addition, sod plays a significant role in the SOD synthetic pathway in A. solani. Results from qRT-PCR showed that the transcriptional expression of these two genes was down-regulated after being treated by VOCs produced by ZD01. These results are useful for a better understanding of the biocontrol mechanism of Bacillus and offer a potential method for potato early blight disease control.

Plant rhizosphere-associated bacterial communities play key roles in affecting host health in response to diverse biotic stresses. Currently, the effect of continuous cropping of potato on soil bacterial communities and physiochemical parameters has not been well documented. Herein, we compared bacterial composition and diversity in rotationally and continuously (5, 10, and 30 years) cropped soils, and clarified the correlations between soil properties and the bacterial communities revealed by Illumina MiSeq sequencing. Our results demonstrated that Proteobacteria, Actinobacteria and Firmicutes were the predominant phyla in all the tested soil samples. While the abundance of Proteobacteria showed an increase, the abundance of Actinobacteria and Firmicutes displayed a reduction with the increase of continuous cropping years. At the genus level, as continuous cropping years increasing, the abundance of Pseudarthrobacter, Bacillus and Pseudomonas decreased, but the abundance of Rhodanobacte, Sphingobium, Mizugakiibacter and Devosia increased. Our results also demonstrated that the abundance of plant growth-promoting rhizobacteria in the rotationally cropped soil was significantly higher than that of continuously cropped soil. Furthermore, our results showed that soil organic matter, available nitrogen, available phosphorus and available potassium were significantly correlated with bacterial community distribution. Overall, our work provides a comprehensive view of altered structure and composition of bacterial communities between the continuously cropped soil and rotationally cropped soil.

Milling tools with a large length–diameter ratio are widely applied in machining structural features with deep depth. However, their high dynamic flexibility gives rise to chatter vibrations, which results in poor surface finish, reduced productivity, and even tool damage. With a passive tuned mass damper (TMD) embedded inside the arbor, a large length–diameter ratio milling tool with chatter-resistance ability was developed. By modeling the milling tool as a continuous beam, the tool-tip frequency response function (FRF) of the milling tool with TMD was derived using receptance coupling substructure analysis (RCSA), and the gyroscopic effect of the rotating tool was incorporated. The TMD parameters were optimized numerically with the consideration of mounting position based on the maximum cutting stability criterion, followed by the simulation of the effectiveness of the optimized and detuned TMD. With the tool-tip FRF obtained, the chatter stability of the milling process was predicted. Tap tests showed that the TMD was able to increase the minimum real part of the FRF by 79.3%. The stability lobe diagram (SLD) was predicted, and the minimum critical depth of cut in milling operations was enhanced from 0.10 to 0.46 mm.

GPR54, Kisspeptin-1 receptor (KISS1R), a member of rhodopsin family, plays a critical role in puberty development and has been proposed to be involved in regulation of energy metabolism. This study aims to explore the function of GPR54 in adipogenesis, lipid metabolism, and obesity in addition to its effect through hormones. Results showed that when fed a high-fat diet, the weight growth of castrated or ovariectomized Gpr54−/− mice was significantly slower than that of WT control, together with a lower triglyceride concentration. The ratio of white adipose tissue was lower, and average size of adipocytes was smaller in Gpr54−/− mice. Meanwhile, there were less adipose tissue macrophages (ATMs), especially pro-inflammatory macrophages. Expression of inflammatory related genes also indicated that inflammatory response caused by obesity was not as drastic in Gpr54−/− mice as in WT mice. Liver triglyceride in Gpr54−/− mice was reduced, especially in female mice. On the other hand, oil drop formation was accelerated when hepatocytes were stimulated by kisspeptin-10 (Kp-10). Primary mesenchymal stem cells (MSCs) of Gpr54−/− mice were less likely to differentiate into adipocytes. When stimulated by Kp-10, 3T3-L1 cell differentiation into adipocytes was accelerated and triglyceride synthesis was significantly promoted. These data indicated that GPR54 could affect obesity development by promoting adipocyte differentiation and triglyceride accumulation. To further elucidate the mechanism, genes related to lipid metabolism were analyzed. The expression of genes involved in lipid synthesis including PPARγ, ACC1, ADIPO, and FAS was significantly changed in Gpr54−/− mice. Among them PPARγ which also participate in adipocyte differentiation displayed a marked reduction. Moreover, phosphorylation of ERK, which involved in GPR54 signaling, was significantly decreased in Gpr54−/− mice, suggesting that GPR54 may promote lipid synthesis and obesity development by activating MAP kinase pathway. Therefore, in addition to the involvement in hormone regulation, our study demonstrated that GPR54 directly participates in obesity development by promoting adipocyte differentiation and fat accumulation. This provided evidence of involvement of GPR54 in lipid metabolism, and revealed new potentials for the identification and development of novel drug targets for metabolic diseases.

Melatonin is a biological hormone that plays crucial roles in stress tolerance. In this study, we investigated the effect of exogenous melatonin on abiotic stress in the tea plant. Under cold, salt and drought stress, increasing malondialdehyde levels and decreasing maximum photochemical efficiency of PSII were observed in tea leaves. Meanwhile, the levels of reactive oxygen species (ROS) increased significantly under abiotic stress. Interestingly, pretreatment with melatonin on leaves alleviated ROS burst, decreased malondialdehyde levels and maintain high photosynthetic efficiency. Moreover, 100 μM melatonin-pretreated tea plants showed high levels of glutathione and ascorbic acid and increased the activities of superoxide dismutase, peroxidase, catalase and ascorbate peroxidase under abiotic stress. Notably, melatonin treatments can positively up-regulate the genes (CsSOD, CsPOD, CsCAT and CsAPX) expression of antioxidant enzyme biosynthesis. Taken together, our results confirmed that melatonin protects tea plants against abiotic stress-induced damages through detoxifying ROS and regulating antioxidant systems.

The initial simulation calculation of the ORC power generation system was carried out using the software Aspen Plus, and the simulation data matched with the design conditions were obtained. According to the specific structure of the evaporator and superheater in the ORC power generation system and the characteristics of the software Aspen EDR, a new simulation calculation method is proposed: structural simulation calculation method. The calculation method and the direct simulation calculation method are used to carry out simulation comparison to find out the regularity of the change of waste heat resources, and it is convenient to further analyze and control the ORC power generation system.

The G protein-coupled receptor TGR5 is a membrane receptor for bile acids. Its agonism increases energy expenditure and controls blood glucose through secretion of glucagon-like peptide-1 in enteroendocrine cells. In this study, we explored the therapeutic potential of WB403, a small compound activating TGR5 which was identified by combining TGR5 targeted luciferase assay and active GLP-1 assay, in treating type 2 diabetes. After confirmation of TGR5 and GLP-1 stimulating activities in various cell systems, WB403 was examined in oral glucose tolerance test, and tested on different mouse models of type 2 diabetes for glycemic control and pancreatic β-cell protection effect. As a result, WB403 exhibited a moderate TGR5 activation effect while promoting GLP-1 secretion efficiently. Interestingly, gallbladder filling effect, which was reported for some known TGR5 agonists, was not detected in this novel compound. In vivo results showed that WB403 significantly improved glucose tolerance and decreased fasting blood glucose, postprandial blood glucose and HbA1c in type 2 diabetic mice. Further analysis revealed that WB403 increased pancreatic β-cells and restored the normal distribution pattern of α-cell and β-cell in islets. These findings demonstrated that TGR5 activator WB403 effectively promoted GLP-1 release, improved hyperglycemia and preserved the mass and function of pancreatic β-cells, whereas it did not show a significant side effect on gallbladder. It may represent a promising approach for future type 2 diabetes mellitus drug development.

To identify factors associated with mother-to-child-transmission and late access to prevention of maternal to child transmission (PMTCT) services among HIV-infected women; and risk factors for infant mortality among HIV-exposed infants in order to assess the feasibility of virtual elimination of vertical transmission and pediatric HIV in this setting.Observational study evaluating the impact of a provincial PMTCT program.The intervention was implemented in 26 counties of Yunnan Province, China at municipal and tertiary health care settings. Log linear regression models with generalized estimating equations were used to identify unadjusted and adjusted correlates for late ARV intervention and MTCT. Cox proportional hazard models with robust sandwich estimation were applied to examine correlates of infant mortality.Mother-to-child- transmission rate of HIV was controlled to 2%, with late initiation of maternal ARV showing a strong association with vertical transmission and infant mortality. Risk factors for late initiation of maternal ARV were age, ethnicity, education, and having a husband not tested for HIV. Mortality rate among HIV-exposed infants was 2.9/100 person-years. In addition to late initiation of maternal ARV, ethnicity, low birth weight and preterm birth were associated with infant mortality.This PMTCT program in Yunnan achieved low rates of MTCT. However the infant mortality rate in this cohort of HIV-exposed children was almost three times the provincial rate. Virtual elimination of MTCT of HIV is an achievable goal in China, but more attention needs to be paid to HIV-free survival.

Routing and spectrum allocation is an important challenge in cognitive wireless mesh networks. A distributed routing and spectrum allocation algorithm with cooperation (DRSAC-W) in cognitive wireless mesh networks is proposed in this paper. In order to show the decrease of the average end-to-end delay with cooperation in DRSAC-W, a distributed routing and spectrum allocation algorithm without cooperation (DRSAC-WO) is proposed in this paper. Minimizing the average end-to-end delay is the objective of DRSAC-W and DRSAC-WO. Simulation results show that the proposed algorithm DRSAC-W with cooperation can alleviate the high delay due to the heterogeneity of available channels of different nodes and achieve low average end-to-end delay.

The classification system, effective reservoir control elements, and major enrichment and exploration modes of helium resources in China are analyzed based on the source of helium, carrier, geological background, and anatomy of typical helium-rich fields. Firstly, based on the special characteristics of helium and the correlation analysis of natural gas accumulation and reservoir formation, we analyzed and sorted out the helium resource and play type classification scheme and classification system in China from nine aspects, namely, the source of helium parental sources, helium type diversities, the storage and carrier types, the technically and economically recoverable characteristics of carrier gases, the carrier gas genesis, the main components of carrier gases, the matching combination of helium sources and reservoirs, background of prototype basin structure, and helium content, to lay the foundation for the subsequent targeted and detailed studies and evaluation programs in different categories. Secondly, the analysis points out the characteristics of helium resource types in the east, middle, and west of China in terms of longitudinal and transverse distribution, tectonic dynamics, geological and geochemical characteristics, and key conditions for the formation of helium deposits. Thirdly, from the perspective of the helium “generation-migration-accumulation” system and the controlling elements and effectiveness of helium-rich reservoir formation, we analyze the effective controlling elements of helium accumulation and the related problems that deserve attention in geological evaluation and point out the misunderstandings in helium reservoir formation and exploration evaluation. Last but not least, from the perspective of basin tectonic background, helium enrichment controlling mechanism and exploration direction, the exploration and evaluation direction and classification scheme for the four element combination zones of “original basin–structure–lithology–carrier gas” helium accumulation in China have been proposed, based on which, four types of basins and eight types of helium-rich zones in China have been sorted out. In these eight types of helium-rich zones, eight typical helium-rich field enrichment and exploration patterns, including the ancient uplift type of China's craton, fracture-fold variant of the craton margin, fracture-rise type of depression basin, slope bulge and uplift type of foreland basin, fracture-convex type of fracture basin, and U/Th-rich basement type of basin were analyzed, and the main controlling factors of the formation of different types of helium-rich deposits were analyzed, which will provide a reference for the subsequent exploration and discovery of similar helium-rich areas and exploration target evaluation. [ABSTRACT FROM AUTHOR]