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Abstract Background Ferroptosis represents a nonapoptotic type of programmed cell death induced by excessive intracellular iron accumulation. Ferroptosis is an essential driver of the pathogenesis of Alzheimer’s disease (AD). Tetrahedral framework nucleic acids (tFNAs) are a novel type of nanoparticle with superior antiapoptotic capacity and excellent biocompatibility. However, the effect of tFNAs on Aβ triggered ferroptosis, cognitive and synaptic impairments in AD remains unknown. Methods N2a cells were treated with Aβ combined with/without tFNAs. Cell viability and levels of Fe2+, lipid peroxidation, MDA, LDH, and GSH were examined. RNA sequencing was applied to explore dysregulated ferroptosis related genes. Seven-month-old APP/PS1 mice were intranasally administrated with tFNAs for two weeks. Fluorescence imaging was used to detect the tFNAs distribution in the brain. Novel object recognition (NOR) test followed by Morris water maze (MWM) was used to test the learning and memory performance of mice. Golgi staining, Western blot, and immunofluorescence staining were used to examine synaptic plasticity. Results tFNAs promoted cell viability and GSH levels, reduced the levels of Fe2+, lipid peroxidation, MDA, and LDH in N2a cells treated with Aβ. RNA sequencing revealed that tFNAs reversed the promotive effect of Aβ on ferroptosis driver Atf3 gene and suppressive effect on ferroptosis suppressors Rrm2 and Furin genes. Fluorescence imaging confirmed the brain infiltration of tFNAs. tFNAs rescued synaptic and memory impairments, and ferroptosis in seven-month-old APP/PS1 mice. Conclusions Collectively, tFNAs inhibited Aβ-mediated ferroptosis and ameliorated cognitive and synaptic impairments in AD mice. tFNAs may serve as novel option to deal with AD. Graphical abstract

Abstract Recombinant adeno-associated viruses (rAAVs) have emerged as an attractive tool for gene delivery, and demonstrated tremendous promise in gene therapy and gene editing—therapeutic modalities with potential “one-and-done” treatment benefits compared to conventional drugs. Given their tropisms for the central nervous system (CNS) across various species including humans, rAAVs have been extensively investigated in both pre-clinical and clinical studies targeting neurodegenerative disease. However, major challenges remain in the application of rAAVs for CNS gene therapy, such as suboptimal vector design, low CNS transduction efficiency and specificity, and therapy-induced immunotoxicity. Therefore, continuing efforts are being made to optimize the rAAV vectors from their “core” genetic payloads to their “coat” or capsid structure. In this review, we describe current approaches for rAAV vector design tailored for transgene expression in the CNS, summarize the development of CNS-targeting AAV serotypes, and highlight recent advancements in AAV capsid engineering, aimed at generating a new generation of rAAVs with improved CNS tropism. Additionally, we discuss various administration routes for delivering rAAVs to the CNS and provide an overview of AAV-mediated gene therapies currently under investigation in clinical trials for the treatment of neurodegenerative diseases.

Abstract Unraveling biodiversity patterns and their driving processes is paramount in ecology and biogeography. However, there remains a limited understanding regarding the underlying mechanisms of community assembly, particularly in alpine streams where significant elevation gradients and habitat heterogeneity exist. We investigated the patterns and drivers of beta diversity, explicitly focusing on taxonomic and functional diversity, in the three parallel rivers region in China. We employed a beta diversity partitioning approach to examine the turnover and nestedness components of beta diversity and further deconstructed the diatom community into attached and unattached groups. Our results revealed distinct diversity patterns and drivers for taxonomic and functional beta diversity. Specifically, taxonomic beta diversity was mainly driven by the turnover component affected by spatial processes, whereas functional beta diversity was dominated by the nestedness component affected by environmental processes. Furthermore, our analysis of the division of the whole communities demonstrated that the varying responses of benthic diatoms with different attached abilities to environmental filtering, dispersal limitation, and directional flow were the essential reasons for shaping the biodiversity patterns of species turnover and functional nestedness in the alpine stream. Our findings suggested that partitioning beta diversity and dividing the entire community can more deeply infer underlying community assembly processes, thereby providing valuable insights into understanding biodiversity patterns, drivers, and conservation strategies.

Abstract Strong uncertainty of renewables puts high demands on the fast response of flexibility resources and resilience‐oriented optimal scheduling for microgrids (MGs). Digital twins (DT) technology based on data‐driven methods is a potential solution to this problem. A DT‐based online resilience scheduling framework for MGs is designed in this study. Based on the proposed framework, a hybrid sequential‐parallel combination method of imitation learning (IL) and deep reinforcement learning (DRL) is proposed to develop the optimal scheduling strategy for MGs. First, a mixed integer second‐order cone programming (MISOCP) model is adopted to behave as an expert to generate decision demonstrations corresponding to operation scenarios of MGs. Then, IL and deep deterministic policy gradient (DDPG) are combined by (1) sequential pretrain and finetune and (2) parallel experience storing and sampling two steps to learn the optimal policy for MGs. Expert demonstrations from the MISOCP model are utilized to pretrain a deep neural network model by IL and initialize the policy network of DDPG to avoid it learning from scratch. Moreover, an expert replay buffer is introduced specifically to avoid forgetting the well‐behaved expert experience and to further accelerate the training process. A 6‐bus MG test system case study demonstrates the effectiveness and scalability of the proposed approach.

Background: Influenza vaccine uptake among healthcare workers is crucial for preventing influenza infections, yet its effectiveness needs further investigation. Objectives: This prospective observational study aimed to assess the protective effect of influenza vaccination among healthcare workers in Shenzhen. Methods: We enrolled 100 participants, with 50 receiving the 2023–2024 quadrivalent influenza vaccine (QIV) and 50 serving as unvaccinated controls. Epidemiological data were collected when the participants presented influenza-like illness. Serum samples were collected at three time points (pre-vaccination and 28 and 180 days after vaccination). Hemagglutination inhibition (HI) assay was performed against the strains included in the 2023–2024 QIV (H1N1, H3N2, BV and BY strains) to assess antibody protection levels. Demographics comparisons revealed no significant differences between the vaccinated and control groups (p > 0.05), ensuring group comparability. Results: The incidence of influenza-like illness was significantly lower in the vaccinated (18%) compared to the control group (36%; p = 0.046; OR = 0.39; 95% CI: 0.15 to 0.98). The vaccinated group also exhibited a higher rate of consecutive two-year vaccinations (48% vs. 24% in the control group, p < 0.05). Additionally, the vaccinated healthcare workers were more inclined to recommend vaccination to their families (80% vs. 48%, p < 0.05). HI titers against H1N1 (p < 0.01), H3N2 (p < 0.01), BV (p < 0.001) and BY (p < 0.01) significantly increased in the vaccinated group at 28 days post-vaccination. Moreover, a marked and sustained increase in HI titers against the H3N2 strain (p < 0.001) was observed at 180 days post-vaccination, highlighting the vaccine’s enduring impact on the immune response. The fold change in the HI titers, indicative of the magnitude of the immune response, was significantly higher for H1N1 (p < 0.01), H3N2 (p < 0.001), BV (p < 0.01) and BY (p < 0.05) among the vaccinated individuals compared to the control group, underscoring the vaccine’s efficacy in eliciting a robust and sustained antibody response. Conclusion: Influenza vaccination significantly reduces the incidence of influenza-like illness among healthcare workers and promotes a sustained immune response. The study supports the importance of annual vaccination for this group to enhance personal and public health.

Reservoirs, heavily influenced by artificial management, often harbor phytoplankton assemblages dominated by cyanobacteria or dinoflagellates, triggering significant changes in aquatic ecosystems. However, due to limited sampling frequency and insufficient attention to species composition, the bloom processes and key characteristics of phytoplankton community structure have not been systematically elucidated. During the low-water level period when blooms are most likely to occur (June to September) in a tributary bay of the Three Gorges Reservoir, daily sampling was conducted to investigate phytoplankton community composition, identify significant environmental factors, and evaluate important structure characteristics of phytoplankton community. The results showed that Microcystis aeruginosa maintained a clear dominance for almost a month in stage 1, with low Shannon and evenness but a high dominance index. Phytoplankton total density and biomass decreased drastically in stage 2, but Microcystis aeruginosa still accounted for some proportion. The highest Shannon and evenness but the lowest dominance index occurred in stage 3. Peridiniopsis niei occurred massively in stage 4, but its dominant advantages lasted only one to two days. NH4-N was responsible for the dominance of Microcystis aeruginosa, while TP and PO4-P was responsible for the dominance of Peridiniopsis niei; however, precipitation contributed to their drastic decrease or disappearance to some extent. The TN : TP ratio could be considered as an important indicator to determine whether Microcystis aeruginosa or Peridiniopsis niei dominated the phytoplankton community. Throughout the study period, physiochemical factors explained more variation in phytoplankton data than meteorological and hydrological factors. Pairwise comparisons revealed an increase in average β diversity with stage progression, with higher β diversities based on abundance data than those based on presence/absence data. Repl had a greater effect on β diversity differences based on presence/absence data, whereas RichDiff had a greater effect on β diversity differences based on species abundance data. Co-occurrence networks for stage 1 showed the most complex structure, followed by stage 4, while the network for stage 3 was relatively sparse, although the overall community division remained compact. This study provides a useful attempt to explore the status and changes in phytoplankton community structure during the bloom process through high-resolution investigation.

Conservation of wetlands on the Qinghai–Tibet Plateau is vital to the ecological security of China and even all of Asia. In this study, we investigated the aquatic protected area system established by the Chinese government in the Qinghai–Tibet Plateau. In general, 9 categories of aquatic protected areas have been established in this area, linked to the International Union for Conservation of Nature classification system of protected areas. The diverse main protection objectives of different protected areas have played a key role in wetland conservation. However, the protection of wetland environments and aquatic organisms has been insufficient in some atypical protected areas and local protected areas. We further constructed a list of important aquatic organisms in the Qinghai–Tibet Plateau and analyzed the protected status of those important species through gap analysis. A total of 156 important aquatic species were identified, with 8 gap species and 18 inadequately protected species. It is encouraging that none of the national key protected species are gap species, but there are 4 gap species that are threatened species on “China’s red list”. In addition, we found that 17 important species are designated as Data Deficient or Not Evaluated on “China’s red list”, including 8 national key protected species. Finally, we propose the prospects for solving the existing problems of aquatic protected area systems: integrating aquatic protected areas, enhancing the status of community-based conservation, and increasing investment in important aquatic organism research.

Abstract Background Synaptic degeneration occurs in the early stage of Alzheimer's disease (AD) before devastating symptoms, strongly correlated with cognitive decline. Circular RNAs (circRNAs) are abundantly enriched in neural tissues, and aberrant expression of circRNAs precedes AD symptoms, significantly correlated with clinical dementia severity. However, the direct relationship between circRNA dysregulation and synaptic impairment in the early stage of AD remains poorly understood. Methods Hippocampal whole-transcriptome sequencing was performed to identify dysregulated circRNAs and miRNAs in 4-month-old wild-type and APP/PS1 mice. RNA antisense purification and mass spectrometry were utilized to unveil interactions between circRIMS2 and methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit (METTL3). The roles of circRIMS2/miR-3968 in synaptic targeting of UBE2K-mediated ubiquitination of GluN2B subunit of NMDA receptor were evaluated via numerous lentiviruses followed by morphological staining, co-immunoprecipitation and behavioral testing. Further, a membrane-permeable peptide was used to block the ubiquitination of K1082 on GluN2B in AD mice. Results circRIMS2 was significantly upregulated in 4-month-old APP/PS1 mice, which was mediated by METTL3-dependent N6-methyladenosine (m6A) modification. Overexpression of circRIMS2 led to synaptic and memory impairments in 4-month-old C57BL/6 mice. MiR-3968/UBE2K was validated as the downstream of circRIMS2. Elevated UBE2K induced synaptic dysfunction of AD through ubiquitinating K1082 on GluN2B. Silencing METTL3 or blocking the ubiquitination of K1082 on GluN2B with a short membrane-permeable peptide remarkably rescued synaptic dysfunction in AD mice. Conclusions In conclusion, our study demonstrated that m6A-modified circRIMS2 mediates the synaptic and memory impairments in AD by activating the UBE2K-dependent ubiquitination and degradation of GluN2B via sponging miR-3968, providing novel therapeutic strategies for AD.

We applied 24-h Holter monitoring to analyze the characteristics of arrhythmias and heart rate variability in Chinese patients with primary aldosteronism (PA) and compared them with age-, sex-, and blood pressure-matched primary hypertension (PH) patients. A total of 216 PA patients and 261 PH patients were enrolled. The nonstudy data were balanced using propensity score matching (PSM), and the risk variables for developing arrhythmias were then analyzed using logistic regression analysis. Before PSM, the proportion of PA patients with combined atrial premature beats and prolonged QT interval was higher than the corresponding proportion in the PH group. After PSM, the PA group had a larger percentage of transient atrial tachycardia and frequent atrial premature beats, and it had higher heart rate variability metrics. The proportion of unilateral PA combined with multiple ventricular premature beats was higher than that of bilateral PA. Older age, grade 3 hypertension, and hypokalemia were independent risk factors for the emergence of arrhythmias in PA patients. PA patients suffer from a greater prevalence of arrhythmias than well-matched PH patients.

Tartary buckwheat (Fagopyrum tataricum Gaertn.) is a coarse grain crop rich in flavonoids that are beneficial to human health because they function as anti-inflammatories and provide protection against cardiovascular disease and diabetes. Flavonoid biosynthesis is a complex process, and relatively little is known about the regulatory pathways involved in Tartary buckwheat. Here, we cloned and characterized the FtMYB163 gene from Tartary buckwheat, which encodes a member of the R2R3-MYB transcription factor family. Amino acid sequence and phylogenetic analysis indicate that FtMYB163 is a member of subgroup 7 (SG7) and closely related to FeMYBF1, which regulates flavonol synthesis in common buckwheat (F. esculentum). We demonstrated that FtMYB163 localizes to the nucleus and has transcriptional activity. Expression levels of FtMYB163 in the roots, stems, leaves, flowers, and seeds of F. tataricum were positively correlated with the total flavonoid contents of these tissues. Overexpression of FtMYB163 in transgenic Arabidopsis enhanced the expression of several genes involved in early flavonoid biosynthesis (AtCHS, AtCHI, AtF3H, and AtFLS) and significantly increased the accumulation of several flavonoids, including naringenin chalcone, naringenin-7-O-glucoside, eriodictyol, and eight flavonol compounds. Our findings demonstrate that FtMYB163 positively regulates flavonol biosynthesis by changing the expression of several key genes in flavonoid biosynthetic pathways.

Different agronomic requirements, production conditions, and crop species result in varying row spacings. To address the issue of seedling damage caused by pressure when a fixed track width sprayer operates in different row spacings and enhance the accuracy of track width adjustment, this study designed a track width adjustment system for a sprayer based on the agronomic requirements for field management during the early and mid-stages of corn growth and the entire growth period of wheat in Henan Province, China. The designed track width adjustment system for the sprayer comprised transmission mechanisms, telescopic track width adjustment mechanisms, and an electro-hydraulic control system. The control system achieved a precise track width adjustment by controlling the movement of the hydraulic cylinders through electrical signals, forming a closed-loop adjustment system with the aid of sensors. Four control schemes are proposed: classical PID, integral separated PID, fuzzy adaptive PID, and integral separated fuzzy PID. Simulation experiments were conducted using MATLAB to compare these schemes. The results indicated that the integral separated fuzzy PID exhibited the fastest response and highest steady-state accuracy. The performance of the track width adjustment system was validated through field experiments. The results demonstrate that the stability coefficient of variation for the track width adjustment was 3.04%, which is below the 10% threshold required by agricultural machinery standards. Additionally, the average error of the track width adjustment was 13.42 mm, indicating high precision and effectively reducing seedling compression damage during plant protection operations.

Microbial community composition, function, and viability are important for biofilm-based sewage treatment technologies. Most studies of microbial communities mainly rely on the total deoxyribonucleic acid (DNA) extracted from the biofilm. However, nucleotide materials released from dead microorganisms may interfere with the analysis of viable microorganisms and their metabolic potential. In this study, we developed a protocol to assess viability as well as viable community composition and function in biofilm in a sewage treatment system using propidium monoazide (PMA) coupled with real-time quantitative polymerase chain reaction (qPCR) and metagenomic technology. The optimal removal of PMA from non-viable cells was achieved by a PMA concentration of 4 μM, incubation in darkness for 5 min, and exposure for 5 min. Simultaneously, the detection limit can reach a viable bacteria proportion of 1%, within the detection concentration range of 102–108 CFU/mL (colony forming unit/mL), showing its effectiveness in removing interference from dead cells. Under the optimal conditions, the result of PMA–metagenomic sequencing revealed that 6.72% to 8.18% of non-viable microorganisms were influenced and the composition and relative abundance of the dominant genera were changed. Overall, this study established a fast, sensitive, and highly specific biofilm viability detection method, which could provide technical support for accurately deciphering the structural composition and function of viable microbial communities in sewage treatment biofilms.

Abstract Background Primary bilateral macronodular adrenal hyperplasia (PMAH) combined with infection by an opportunistic pathogen is complicated. Clinical evidence on managing PMAH patients with infections by opportunistic pathogens is insufficient. Case presentation A 66-year-old male was admitted with bilateral adrenal masses and was diagnosed with PMAH. Fever and disturbance of consciousness appeared after laparoscopic left adrenalectomy. Cryptococcal meningitis was confirmed by cerebrospinal fluid (CSF) culture. The exacerbation of his medical condition was suspected to result from immune reconstitution inflammatory syndrome (IRIS), and he had been treated with antifungal therapy and glucocorticoid replacement, but he responded poorly and eventually died of multiorgan failure. We summarized the clinical observations of 12 Cushing's syndrome (CS) patients infected by Cryptococcus. Seven out of nine patients who were treated for cryptococcus infection before receiving CS survived, while three patients treated for cryptococcus infection after CS treatment developed signs of IRIS and eventually died. Conclusion Cushing's syndrome, complicated with cryptococcal infection, has a high mortality rate, mainly when IRIS emerges. Carefully identifying the presence of the suspected infection, and controlling cryptococcal infection before removing the culprit adrenals could be the rational choice.

The vertical distribution of phytoplankton plays a crucial role in shaping the dynamics and structure of aquatic communities. In highly dynamic reservoir systems, water level fluctuations significantly affect the physiochemical conditions and the phytoplankton community. However, the specific effects on the vertical characteristics of phytoplankton between the mainstream and the tributary bay of the reservoir remain unstudied. This study investigated the vertical aspects of phytoplankton density, biomass, α and β diversity through monthly sampling over two years in the mainstream (Chang Jiang, CJ) and a tributary bay (Xiang Xi, XX) of the Three Gorges Reservoir in China. Phytoplankton density and biomass were significantly higher in XX, indicating an increased risk of algal blooms in the tributary. The phytoplankton community in CJ showed more stable species-environment relationships, a lower Shannon index and a higher evenness index, suggesting a relatively simple structure and a more uniform distribution of phytoplankton among different water layers. Conversely, XX showed greater differences between water layers (higher β diversity), with significant negative correlations with water level and positive correlations with DO difference, dissolved silica (DSi) difference, and stratification. Peak phytoplankton density and biomass, as well as high β diversity in XX, occurred during periods of decreased water levels with strong stratification in spring and summer. A structural equation model complemented by path analysis revealed that a decrease in water level could increase β diversity either directly through internal processes with extended residence time or indirectly by modifying stratification and the vertical distribution of DSi in XX. Therefore, a proposed water quality management strategy for XX was to increase the water level or reduce β diversity by implementing artificial mixing during stratification periods. Overall, this study lies in its comprehensive investigation of the vertical characteristics of the phytoplankton community in both the mainstream and the tributary bay of the Three Gorges Reservoir, elucidating the significant impact of water level fluctuations and providing insights for targeted water quality management strategies in the tributary bay to mitigate potential ecological impacts.

ABSTRACTModifications on viral RNAs (vRNAs), either genomic RNAs or RNA transcripts, have complex effects on the viral life cycle and cellular responses to viral infection. The advent of Oxford Nanopore Technologies Direct RNA Sequencing provides a new strategy for studying RNA modifications. To this end, multiple computational tools have been developed, but a systemic evaluation of their performance in mapping vRNA modifications is lacking. Here, 10 computational tools were tested using the Sindbis virus (SINV) RNAs isolated from infected mammalian (BHK-21) or mosquito (C6/36) cells, with in vitro-transcribed RNAs serving as modification-free control. Three single-mode approaches were shown to be inapplicable in the viral context, and three out of seven comparative methods required cutoff adjustments to reduce false-positive predictions. Utilizing optimized cutoffs, an integrated analysis of comparative tools suggested that the intersected predictions of Tombo_com and xPore were significantly enriched compared with the background. Consequently, a pipeline integrating Tombo_com and xPore was proposed for vRNA modification detection; the performance of which was supported by N6-methyladenosine prediction in severe acute respiratory syndrome coronavirus 2 RNAs using publicly available data. When applied to SINV RNAs, this pipeline revealed more intensive modifications in subgenomic RNAs than in genomic RNAs. Modified uridines were frequently identified, exhibiting substantive overlapping between vRNAs generated in different cell lines. On the other hand, the interpretation of other modifications remained unclear, underlining the limitations of the current computational tools despite their notable potential.IMPORTANCEComputational approaches utilizing Oxford Nanopore Technologies Direct RNA Sequencing data were almost exclusively designed to map eukaryotic epitranscriptomes. Therefore, extra caution must be exercised when using these tools to detect vRNA modifications, as in most cases, vRNA modification profiles should be regarded as unknown epitranscriptomes without prior knowledge. Here, we comprehensively evaluated the performance of 10 computational tools in detecting vRNA modification sites. All tested single-mode methods failed to differentiate native and in vitro-transcribed samples. Using optimized cutoff values, seven tested comparative tools generated very different predictions. An integrated analysis showed significant enrichment of Tombo_com and xPore predictions against the background. A pipeline for vRNA modification detection was proposed accordingly and applied to Sindbis virus RNAs. In conclusion, our study underscores the need for the careful application of computational tools to analyze viral epitranscriptomics. It also offers insights into alphaviral RNA modifications, although further validation is required.

Cadmium (Cd) is a naturally occurring toxic heavy metal that adversely affects plant germination, growth, and development. While the effects of Cd have been described on many crop species including rice, maize, wheat and barley, few studies are available on cadmium’s effect on Tartary buckwheat which is a traditional grain in China. We examined nine genotypes and found that 30 µM of Cd reduced the root length in seedlings by between 4 and 44% and decreased the total biomass by 7 to 31%, compared with Cd-free controls. We identified a significant genotypic variation in sensitivity to Cd stress. Cd treatment decreased the total root length and the emergence and growth of lateral roots, and these changes were significantly greater in the Cd-sensitive genotypes than in tolerant genotypes. Cd resulted in greater wilting and discoloration in sensitive genotypes than in tolerant genotypes and caused more damage to the structure of root and leaf cells. Cd accumulated in the roots and shoots, but the concentrations in the sensitive genotypes were significantly greater than in the more tolerant genotypes. Cd treatment affected nutrient uptake, and the changes in the sensitive genotypes were greater than those in the tolerant genotypes, which could maintain their concentrations closer to the control levels. The induction of SOD, POD, and CAT activities in the roots and shoots was significantly greater in the tolerant genotypes than in the sensitive genotypes. We demonstrated that Cd stress reduced root and shoot growth, decreased plant biomass, disrupted nutrient uptake, altered cell structure, and managed Cd-induced oxidative stress differently in the sensitive and tolerant genotypes of Tartary buckwheat.

The effect of combination therapies in many cancers has often been shown to be superior to that of monotherapies. This success is commonly attributed to drug synergies. Combinations of two (or more) drugs in xenograft tumor growth inhibition (TGI) studies are typically designed at fixed doses for each compound. The available methods for assessing synergy in such study designs are based on combination indices (CI) and model-based analyses. The former methods are suitable for screening exercises but are difficult to verify in in vivo studies, while the latter incorporate drug synergy in semi-mechanistic frameworks describing disease progression and drug action but are unsuitable for screening. In the current study, we proposed the empirical radius additivity (Rad-add) score, a novel CI for synergy detection in fixed-dose xenograft TGI combination studies. The Rad-add score approximates model-based analysis performed using the semi-mechanistic constant-radius growth TGI model. The Rad-add score was compared with response additivity, defined as the addition of the two response values, and the bliss independence model in combination studies derived from the Novartis PDX dataset. The results showed that the bliss independence and response additivity models predicted synergistic interactions with high and low probabilities, respectively. The Rad-add score predicted synergistic probabilities that appeared to be between those predicted with response additivity and the Bliss model. We believe that the Rad-add score is particularly suitable for assessing synergy in the context of xenograft combination TGI studies, as it combines the advantages of CI approaches suitable for screening exercises with those of semi-mechanistic TGI models based on a mechanistic understanding of tumor growth.

Abstract Introduction Although aerobic physical exercise may improve osteoporosis during ageing, the underlying mechanism of the favorable effects remains unclear. The aim of this study was to examine the localized and generalized proinflammatory indicators and the adaptive skeletal responses to treadmill training in aged rats to explore the potential mechanisms by which treadmill training impacts bone deterioration in a natural aged rat model. Materials and methods A total of 24 Sprague Dawley (SD) rats were included in this study. Sixteen of all these animals were twenty-four months natural aged male SD rats, which were distributed into two groups (n = 8/group): AC group with sham treadmill training, and AT group with 8 weeks treadmill training. The remaining 8 were six months male SD rats matched subline and supplier, which were used as the adult control group with sham treadmill training (YC group, n = 8). The serum, bone marrow, fresh femur, tibia, and lumbar spine were harvested for molecular biological analysis, bone mineral density (BMD) testing, and micro-CT analysis after 8 weeks of treadmill training. Results After 8 weeks of intervention, the results showed that treadmill training increased BMD and inhibited deterioration of bone microarchitecture of hind limb bones. Further analysis showed that treadmill training increased serum P1CP concentration and decreased serum CTX-1level. Interestingly, treadmill training down-regulated the protein expressions of proinflammatory indicators, including NLRP3, proCaspase1, cleaved Caspase1, IL-1β, and GSDMD-N, and the mRNA levels of NLRP3, Caspase1, and IL-1β of the bone marrow. In addition, treadmill training also inhibited serum TNF-α and IL-1β concentration. However, 8 weeks of treadmill training did not increase BMD and bone microarchitecture in the lumbar spine. Conclusion Treadmill training mitigates the ageing-induced bone loss and reverses the deterioration of bone microarchitecture in hind limbs probably through inhibiting NLRP3/Caspase1/IL-1β signaling to attenuate low-grade inflammation and improve the inflammatory bone microenvironment.

To solve the issue of unsatisfactory recruitment of mesenchymal stem cells (MSCs) around implant in osteoporotic fractures, we fabricated a ROS-responsive system on titanium surface through hydroxyapatite coating and biomolecule grafting. The porous hydroxyapatite and phosphorylated osteogenic growth peptides (p-OGP) were introduced onto titanium surface to synergistically improve osteogenic differentiation of MSCs. After the p-OGP-promoted expression of osteogenic related proteins, the calcium and phosphate ions were released through the degradation of hydroxyapatite and integrated into bone tissues to boost the mineralization of bone matrix. The ROS-triggered release of DNA aptamer (Apt) 19S in the osteoporotic microenvironment guides MSC migration to implant site due to its high affinity with alkaline phosphatase on the membrane of MSCs. Once MSCs reached the implant interface, their osteogenic differentiation potential was enhanced by p-OGP and hydroxyapatite to promote bone regeneration. The study here provided a simple and novel strategy to prepare functional titanium implants for osteoporotic bone fracture repair.

Key Clinical Message A 31‐year‐old female with a diagnosis of bipolar disorder developed black hairy tongue after alprazolam therapy. Her symptom resolved 10 days after the cessation of alprazolam. Abstract Alprazolam is a widely used antidepressant and antianxiety drug. Mild to moderate side effect of alprazolam was commonly seen, including lethargy, dizziness, headache, dry mouth, nausea, fatigue, constipation, and blurred vision. In this case, we reported a patient developed black hairy tongue after alprazolam intake, and her symptom resolved after 10‐day discontinuation of alprazolam. This rare adverse event should be of concern to clinicians. This is the first paper to report an alprazolam‐induced BHT. This rare side effect of alprazolam should be concern of clinicians; we hope our report will promote the understand of BHT and acknowledge clinicians of this rare side effect of alprazolam.

Background: Allergen immunotherapy is the only etiological treatment for allergic rhinitis. Objective: To analyze the efficacy, safety, and mechanism of subcutaneous immunotherapy (SCIT). Methods: The efficacy, safety, and serum immunological changes of 3 modes of subcutaneous immunotherapy were compared. Peripheral blood mononuclear cells (PBMC) transcriptome changes were obtained on the Illumina sequencing platforms. We confirmed differentially expressed genes (DEGs) by quantitative real-time polymerase chain reaction (PCR). The DEGs were analyzed by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) networks. The correlation between the common DEGs and clinical indicators was analyzed by Origin 2022. Results: The 3 SCITs were all effective after 1 year. The Combined Symptom and Medication Score (CSMS) and Visual Analog Score (VAS) in rush immunotherapy (RIT) are lowest after 24 and 48 weeks of treatment among the 3 groups. After treatment, the levels of sIgE, sIgE/tIgE, Th2 cytokines, Th17 cytokines, and percentage of peripheral eosinophils (EOS%) decreased significantly (P＜0.05), while the levels of Th1 type cytokines did not change significantly. Transcriptome analysis identified 24, 24, and 91 DEGs at W3 and 42, 52, 175 DEGs at W7 in conventional immunotherapy (CIT), cluster immunotherapy (CLIT), and RIT groups, respectively. The pathways and functions involved in SCIT include secretion of Th1/2 cytokines, immune cell differentiation. Unlike CIT and CLIT, DEGs are also involved in T cell tolerance induction, T cell anergy, and lymphocyte anergy in RIT. CXCR1, CXCR2, and IER3 had a specific effect on reflecting the improvement of symptoms in allergic rhinitis patients with SCIT. Conclusion: The clinical efficacy of RIT appeared earlier than CIT and CLIT. Clinicians can use the highly conserved gene expression profile to evaluate responses to immunotherapy.

BackgroundAlthough previous sporadic studies have reported the associations between a few autoimmune diseases and nasal polyps, these studies have limitations such as conflicting results, small sample sizes, and low levels of evidence.MethodsSeveral autoimmune diseases were selected as exposures while the nasal polyps were selected as outcomes. Bidirectional univariable Mendelian randomization and multivariable Mendelian randomization analyses were performed after rigorous screening of instrumental variables. Then mediation analyses were conducted to further investigate the underlying mechanisms.ResultsFor the first time, we investigated the causal relationships between nine autoimmune diseases and nasal polyps in different genders and found: (1) there was a causal association between adult-onset Still's disease and nasal polyps; (2) sarcoidosis, ulcerative colitis, type 1 diabetes, and Crohn’s disease had no significant associations with nasal polyps; (3) celiac disease showed a suggestive positive association with female nasal polyps, whereas juvenile arthritis and multiple sclerosis showed suggestive positive associations with male nasal polyps. By contrast, arthropathic psoriasis showed a suggestive negative association with nasal polyps. In addition to these nine diseases, previous controversial issues were further investigated: (1) there was a causal relationship between rheumatoid arthritis and nasal polyps, which was partially mediated by “BAFF-R for IgD+ B cells”; (2) ankylosing spondylitis showed suggestive positive associations with the female but not the male nasal polyps. Besides, we validated that there was no causal effect of autoimmune hyperthyroidism on nasal polyps.ConclusionSpecific conclusions regarding the causal effects of multiple autoimmune diseases on nasal polyps are the same as above. By comparing results between different genders, we have initially observed the sex bimodality in the causal effects between autoimmune diseases and nasal polyps, with those on male nasal polyps being stronger than those on female nasal polyps. Our study lays a solid foundation for further research in the future, not only helping identify individuals susceptible to nasal polyps early but also improving our understanding of the immunopathogenesis of these heterogeneous diseases.

Biodiversity and ecosystem functioning (BEF) relationships are important research issues in the context of biodiversity loss. However, most studies only explored BEF relationships using species richness as a proxy for biodiversity without considering the effects of species evenness and importance of functional diversity on ecosystem functioning. In the present study, we explored multiple relationships among in-stream environmental variables, species diversity (species richness and species evenness), functional diversity (functional richness, functional evenness and Rao’s quadratic entropy index) and biomass of benthic diatom communities from a Chinese mountainous river network. We tested two hypotheses: (1) species richness and evenness affect community biomass independently, and (2) species diversity directly affects community biomass and also indirectly affects community biomass by influencing functional diversity. We found that benthic diatom diversity and biomass were influenced by wetted width, conductivity, and pH. Species richness and evenness had positive and negative effects on community biomass, respectively; while, the effect of richness (with a pathway coefficient of 0.39) was stronger than that of evenness (−0.28). However, we have not found an interaction pathway between species richness and species evenness in structural equation models, indicating that the two effects on community biomass were independent of each other. Both functional richness and Rao’s quadratic entropy index had positive effects on community biomass, although effects of other variables blurred the relationship between functional richness and community biomass in structural equation modeling. Besides direct effects, species diversity also indirectly affected community biomass through influencing Rao’s quadratic entropy index, with direct effects (0.27) were more than twice stronger than indirect effects (0.12). Our findings imply that the selection effect played a dominant role in the relationship between diatom diversity and biomass, indicated by the negative species evenness and biomass relationship; meanwhile, the complementarity effect was also important. The inclusion of more diversity indices to explore the biodiversity-biomass relationship would help to provide a deeper and more comprehensive understanding of this relationship and its driving mechanisms. We suggest carrying out more studies on BEF relationships in streams and rivers to support protection practices for sustaining biodiversity and their ecosystem functions in natural lotic ecosystems.

In this study, we evaluated the ecological water quality of the entire Three Gorges Reservoir (TGR) and further examined the relationship with changes in watershed land covers. Using the phytoplankton functional group-based Q index, we found that the ecological water quality in the mainstream (previously known as the Yangtze River) of TGR is good, with 84% of sites in the status above good. While the poor ecological water quality was generally observed in the backwater regions of TGR’s tributaries, with 79% of sites below the good status. Further investigating the potential impacts of the changes in land covers within the watershed on the tributary ecological water quality, we found that the percentage of urban and farmland areas had a significant (p < 0.05) negative correlation with the Q index-based ecological water quality of the tributary bays, and the forest cover had a marginally significant (p = 0.058) positive correlation with the ecological water quality. As a comparison, total nitrogen and total phosphorus in the tributary backwater regions of TGR had no reasonable correlation with the land covers within the watershed. Our study highlights that watershed management can enhance the ecological water quality in the backwater regions of TGR’s tributaries, but it likely to be a long-term process. This implies considerations of other rapid measures, such as the water level regulation approach, should also be considered in reservoir management. Our study underscores the importance of ecological water quality assessment in reservoir management and provides insights into the impacts of changes in watershed land covers on ecological water quality in backwater regions of TGR’s tributaries.

The effect of biodiversity on ecosystem productivity has been a controversial issue in ecological research. The species richness–productivity relationship is highly variable in natural ecosystems, with a positive relationship being one of the most commonly observed relationships. Previous regional studies from terrestrial ecosystems have demonstrated that environmental gradients can regulate the species richness–productivity relationship. However, how this relationship varies in freshwater ecosystems across spatial environment gradients remains unclear. In this study, we propose that the species richness–productivity relationship can be modulated by the water depth. Here, we surveyed the submerged macrophyte community structure by establishing 24 transects and 642 quadrats in Erhai Lake, Yunnan Plateau, China. Our findings highlight that the species richness–productivity relationship gradually changed from slightly positive to strongly positive as the environment became more light-limited with the increasing water depth, supporting the stress-gradient hypothesis. The results from this study provide new insights into the biodiversity–ecosystem functioning relationships and in managing lake macrophyte communities and productivity.

Improper management of aquatic environments substantially restricts the development of the aquaculture industry. The industrialisation of the crayfish Procambarus clarkii, for example, is currently being limited by poor water quality. Research suggests that microalgal biotechnology has a great potential for water quality regulation. However, the ecological effects of microalgal applications on aquatic communities in aquaculture systems remain largely unknown. In the present study, 5 L Scenedesmus acuminatus GT-2 culture (biomass 120 g L-1) was added to an approximately 1,000 m2 rice-crayfish culture to examine the response of aquatic ecosystems to microalgal application. The total nitrogen content decreased significantly as a result of microalgal addition. Moreover, the microalgal addition changed the bacterial community structure directionally and produced more nitrate reducing and aerobic bacteria. The effect of microalgal addition on plankton community structure was not obvious, except for a significant difference in Spirogyra growth which was inhibited by 81.0% under microalgal addition. Furthermore, the network of microorganisms in culture systems with the added microalga had higher interconnectivity and was more complex, which indicating microalgal application enhance the stability of aquaculture systems. The application of microalgae was found to have the greatest effect on the 6th day of the experiment, as supported by both environmental and biological evidence. These findings can provide valuable guidance for the practical application of microalgae in aquaculture systems.

Abstract Background Mood disorder, impulsivity and aggression are common in drug users compared to healthy controls. However, no study has focused on the difference in various types of drug users. Therefore, the objective of this study was to explore the differences in depression, anxiety, impulsivity, and aggression among methamphetamine, heroin and polysubstance users and to further explore the risk factors for severe depression in the three groups. Methods Drug users over 18 years old who met the DSM-V diagnostic criteria for substance -related disorders were included in the study. All participants completed a general questionnaire, the Zung Self-Rating Depression Scale (SDS), the Zung Self-Rating Anxiety Scale (SAS), Barratt impulsiveness Scale Version 11 (BIS-11), and the Buss-Perry Aggression Questionnaire (BPAQ). One-way ANOVAs or Chi-square tests were used to test the differences among the groups, correlation analysis was used to test the relationship between drug use and other parameters, and multiple logistic regression was conducted to assess the risk factors for severe depression. Results A total of 1,486 participants were included, comprising 86.3% males with a mean age of 38.97 years. There was a significant difference in the percentage of severe depression and SDS scores among the three groups, but no significant difference was found in SAS, BIS-11 and BPAQ scores. Using methamphetamines, hostility and anxiety were risk factors for developing severe depression in all the participants and anxiety remained constant in the other three groups. Moreover, methamphetamine use was 2.16 and 3.35 times more likely to cause severe depression than heroin and polysubstance use, respectively. The initial age of substance use was negatively correlated with BPAQ, SAS, and SDS scores, whereas the drug use duration and addiction duration were positively correlated. Conclusions In this study, we found that the highest prevalence of severe depression was in participants using methamphetamines and that using methamphetamines, hostility, and anxiety were risk factors for developing severe depression. This result addressed an important gap in our knowledge of the different characteristics of depression, anxiety, impulsivity and aggression in various types of substance users and provides clinicians and policy-makers with directions for intervention and preventing relapse.

The article briefly describes the importance of furrowing depth stability for seed germination and growth under precision seeding conditions. By analyzing the application status of furrowing depth control technology of the planter globally, the research method, technical characteristics, and development of furrowing depth stability control technology are reviewed from three key aspects, namely, profiling adjustment device, furrowing depth detection technology, and automatic control system. In this paper, (1) two types of profiling adjustments, active and passive, are described based on the difference in the downforce adjustment method; (2) three furrowing depth detection methods are described based on different sensors; (3) and three ways of regulating the furrowing depth system are summarized based on the different ways of evaluating the stability of furrowing depth. In addition, the characteristics and application requirements of global furrow depth control technology are summarized. It is proposed that the future planter should be developed in the direction of automatic navigation, automatic monitoring and evaluation of seeding quality, variable seeding, high-speed seeding, and other intelligent precision seeding techniques. The summary and outlook of this paper aim to promote the overall development of furrowing depth control technology.

Abstract Background Elymus breviaristatus and Elymus sinosubmuticus are perennial herbs, not only morphologically similar but also sympatric distribution. The genome composition of E. sinosubmuticus has not been reported, and the relationship between E. sinosubmuticus and E. breviaristatus is still controversial. We performed artificial hybridization, genomic in situ hybridization, and phylogenetic analyses to clarify whether the two taxa were the same species. Results The high frequency bivalent (with an average of 20.62 bivalents per cell) at metaphase I of pollen mother cells of the artificial hybrids of E. breviaristatus (StYH) × E. sinosubmuticus was observed. It illustrated that E. sinosubmuticus was closely related to E. breviaristatus. Based on genomic in situ hybridization results, we confirmed that E. sinosubmuticus was an allohexaploid, and the genomic constitution was StYH. Phylogenetic analysis results also supported that this species contained St, Y, and H genomes. In their F1 hybrids, pollen activity was 53.90%, and the seed setting rate was 22.46%. Those indicated that the relationship between E. sinosubmuticus and E. breviaristatus is intersubspecific rather than interspecific, and it is reasonable to treated E. sinosubmuticus as the subspecies of E. breviaristatus. Conclusions In all, the genomic constitutions of E. sinosubmuticus and E. breviaristatus were StYH, and they are species in the genus Campeiostachys. Because E. breviaristatus was treated as Campeistachys breviaristata, Elymus sinosubmuticus should be renamed Campeiostachys breviaristata (Keng) Y. H. Zhou, H. Q. Zhang et C. R. Yang subsp. sinosubmuticus (S. L. Chen) Y. H. Zhou, H. Q. Zhang et L. Tan.

ABSTRACT Most alphaviruses are transmitted by mosquito vectors and infect a wide range of vertebrate hosts, with a few exceptions. Eilat virus (EILV) in this genus is characterized by a host range restricted to mosquitoes. Its chimeric viruses have been developed as safe and effective vaccine candidates and diagnostic tools. Here, we investigated the interactions between these insect-specific viruses (ISVs) and mosquito cells, unveiling their potential roles in determining vector competence and arbovirus transmission. By RNA sequencing, we found that these ISVs profoundly modified host cell gene expression profiles. Two EILV-based chimeras, consisting of EILV’s nonstructural genes and the structural genes of Chikungunya virus (CHIKV) or Venezuelan equine encephalitis virus (VEEV), namely, EILV/CHIKV (E/C) and EILV/VEEV (E/V), induced more intensive transcriptome regulation than parental EILV and activated different antiviral mechanisms in host cells. We demonstrated that E/C robustly promoted antimicrobial peptide production and E/V strongly upregulated the RNA interference pathway components. This also highlighted the intrinsic divergences between CHIKV and VEEV, representatives of the Old World and New World alphaviruses. In contrast, EILV triggered a limited antiviral response. We further showed that initial chimera infections efficiently inhibited subsequent pathogenic alphavirus replication, especially in the case of E/V infection, which almost prevented VEEV and Sindbis virus (SINV) superinfections. Altogether our study provided valuable information on developing ISVs as biological control agents. IMPORTANCE Mosquito-borne alphaviruses can cause emerging and reemerging infectious diseases, posing a considerable threat to human and animal health worldwide. However, no specific antivirals or commercial vaccines are currently available. Therefore, it is vital to develop biological control measures to contain virus transmission. Insect-specific EILV and its chimeras are supposed to induce superinfection exclusion owing to the close phylogenetical relationship with pathogenic alphaviruses. These viruses might also, like bacterial symbionts, modulate mosquito hosts’ vector competence for arboviruses. However, little is known about the responses of mosquitoes or mosquito cells to ISV infections. Here, we found that EILV barely elicited antiviral defenses in host cells, while its chimeras, namely, E/C and E/V, potentiated the responses via different mechanisms. Furthermore, we showed that initial chimera infections could largely inhibit subsequent pathogenic alphavirus infections. Taken together, our study proposed insect-specific chimeras as a promising candidate for developing biological control measures against pathogenic alphaviruses.

Abstract Background The correct identification of pills is very important to ensure the safe administration of drugs to patients. Here, we use three current mainstream object detection models, namely RetinaNet, Single Shot Multi-Box Detector (SSD), and You Only Look Once v3(YOLO v3), to identify pills and compare the associated performance. Methods In this paper, we introduce the basic principles of three object detection models. We trained each algorithm on a pill image dataset and analyzed the performance of the three models to determine the best pill recognition model. The models were then used to detect difficult samples and we compared the results. Results The mean average precision (MAP) of RetinaNet reached 82.89%, but the frames per second (FPS) is only one third of YOLO v3, which makes it difficult to achieve real-time performance. SSD does not perform as well on the indicators of MAP and FPS. Although the MAP of YOLO v3 is slightly lower than the others (80.69%), it has a significant advantage in terms of detection speed. YOLO v3 also performed better when tasked with hard sample detection, and therefore the model is more suitable for deployment in hospital equipment. Conclusion Our study reveals that object detection can be applied for real-time pill identification in a hospital pharmacy, and YOLO v3 exhibits an advantage in detection speed while maintaining a satisfactory MAP.

BackgroundDepression and anxiety are major psychological issues among patients with tuberculosis (TB) owing to chronic and complex treatments, have been reported to be closely correlated with immune and inflammation. However, the association of peripheral immune-inflammatory characteristics with depression/anxiety symptoms in in-patients with TB has rarely been reported.MethodsA cross-sectional study of 338 in-patients with TB from 3 hospitals in China were enrolled to investigate their depression and anxiety status by using the nine-item Patient Health Questionnaire (PHQ-9) and seven-item Generalized Anxiety Disorder Scale (GAD-7). Participants were divided into groups based on their PHQ-9 and GAD-7 scores, and differences in demography and immune-inflammatory characteristics were studied. Logistic analysis was performed to explore factors related to depression and anxiety symptoms.ResultsDepression and anxiety prevalence among patients with TB was 47.9 and 42.6%, respectively. Furthermore, 38.5% of patients reported a comorbidity of depression and anxiety symptoms. The counts of CD3, CD4, CD8, and lymphocytes decreased, whereas those of neutrophils, platelets, and peripheral blood cells and their derived indices increased among TB patients with depression or anxiety in comparison with those without symptoms (p < 0.05). In addition, increasing age, lower income (monthly income ≤ 3,000 yuan), divorced or widowed, drug resistance, and higher systemic immune inflammation index (SII) were significantly associated with depression or anxiety symptoms (p < 0.05).ConclusionApproximately half of the patients with TB suffered from depression or/and anxiety symptoms. Patients with depression or anxiety present worse cell immune status and stronger inflammatory responses compared to those without symptoms. We emphasized the importance of paying attention to the dysfunction of immune-inflammation process of TB patients with depression or anxiety symptoms. Especially, SII has a potential application value in guiding the evaluation of TB-related depression or anxiety owing to its easily accessibility and being economical.

The biodiversity-stability relationship is a fundamental subject of ecological research. Considerable evidence demonstrates that biodiversity can either increase or decrease stability. Most relevant research mainly focuses on grassland and forest ecosystems. The biodiversity-stability relationship in aquatic ecosystems and the underlying mechanisms remain poorly understood. To fill the gap, we conducted a year-long study on the phytoplankton of reservoir ecosystems in the Xiangxi Bay of Three Gorges Reservoir (TGR) to test the following hypotheses: (H1) phytoplankton species richness and functional diversity directly reduce phytoplankton community stability in reservoir ecosystems; (H2) nutrient enrichment and water temperature increasing directly reduce phytoplankton community stability; and (H3) nutrients and water temperature indirectly reduce phytoplankton community stability via biodiversity. The structural equation model (SEM) found that functional diversity (community-weighted means of traits and functional divergence) had significant negative correlations with phytoplankton community stability (p < 0.05), while the species diversity had no significant correlation with phytoplankton community stability (p > 0.05). This finding partially supported the hypothesis H1, which suggested that the functional diversity had a closer tie with stability than the species diversity. SEM did not find any direct effect of environmental factors on phytoplankton community stability, which rejected our hypothesis H2. Instead, SEM found that water temperature and phosphate decreased phytoplankton community stability by increasing the first principal component of the community-weighted means of traits (CWM_PC1), which supported hypothesis H3. Further analysis showed that the increased water temperature and phosphate concentration can promote “r-strategists” species (larger CWM_PC1), which are less resistant to environmental disturbances, therefore decreasing the phytoplankton community stability. Our study highlights the importance of functional diversity in maintaining the relationship between biodiversity and stability in the phytoplankton community, which may provide a mechanistic understanding of the biodiversity-stability relationships in aquatic ecosystems.

Diabetic retinopathy (DR) is increasingly becoming a main complication of diabetes, and is difficult to cure. In our research, network pharmacology analysis suggested that both compound Danshen dripping pills (CDDP) and bezafibrate (BZF) have potential protective effects against DR and the two drugs may act synergistically. The pharmacological effects of the coadministration of CDDP and BZF were elucidated in db/db mice, which simulate DR. Fluorescein fundus angiography showed that coadministration attenuated vascular leakage. Optical coherence tomography and hematoxylin and eosin staining showed that coadministration improved retinal thickness better than CDDP monotherapy. In addition, cell fluorescence images of reactive oxygen species revealed that coadministration of CDDP and BZF had more potent effects against oxidative stress than CDDP monotherapy. Metabolomics analysis showed that coadministration reduced the ratio of oxidized glutathione to reduced glutathione further than CDDP monotherapy. Coadministration of CDDP and BZF may provide additional protective effects by resisting vascular leakage, increasing retinal thickness, and inhibiting inflammation and oxidative stress in DR.

BackgroundInsomnia is the most common comorbidity in children with autism spectrum disorder (ASD) and seriously affects their rehabilitation and prognosis. Thus, an intervention targeting insomnia in ASD seems warranted. Repetitive transcranial magnetic stimulation (rTMS), a potentially effective treatment for improving sleep quality and optimizing sleep structure, has already been demonstrated to alleviate insomnia symptoms and sleep disturbance in different neurological and neuropsychiatric conditions. This trial aims to investigate the effects of rTMS on insomnia in patients with ASD.MethodThis study is designed to be a double-blind, randomized, and sham-controlled trial with a target sample size of 30 participants (aged 3–13 years) diagnosed with ASD comorbid with insomnia. The intervention phase will comprise 20 sessions of rTMS or sham rTMS applied over the right dorsolateral prefrontal cortex (DLPFC) within four consecutive weeks. The effect of rTMS on insomnia and other symptoms of ASD will be investigated through home-PSG (two consecutive overnights), sleep diary, CSHQ, CARS, ABC, SRS, RBS-R, and metabolomics analysis at baseline and posttreatment. A follow-up assessment 1 month after the intervention will examine the long-term effects.DiscussionThe results of this study may address an important knowledge gap and may provide evidence for the use of rTMS to treat insomnia in ASD. Furthermore, it will elucidate the potential mechanism and link between sleep disorders and clinical symptoms.Clinical trial registrationThe study is ongoing and has been registered at the Chinese Clinical Trial Registry (ChiCTR2100049266) on 28/07/2021.

BackgroundReminiscence therapy mitigates psychological issues and improves the quality of life of cancer survivors. However, its role in elderly patients with hepatocellular carcinoma (HCC) is unclear. Thus, we aimed to detect the effect of reminiscence therapy on anxiety, depression, and the quality of life of elderly patients with HCC.MethodsIn total, 106 elderly patients with HCC after resection were randomized in a 1:1 ratio to the reminiscence therapy group (N = 54) and control care group (N = 52) and then received intervention for 12 months. Anxiety and depression were evaluated by the Hospital Anxiety and Depression Scale (HADS) at baseline [Month (M) 0], 3 months (M3), 6 months (M6), 9 months (M9), and 12 months (M12). Meanwhile, quality of life was assessed using the European Organization for Research and Treatment of Cancer quality of life Questionnaire—Core 30 (QLQ-C30) at M0, M6, and M12.ResultsThe HADS for anxiety score at M9 (6.8 ± 2.3 vs. 7.8 ± 2.4, P = 0.039) and M12 (6.6 ± 2.4 vs. 7.8 ± 2.6, P = 0.013) and the anxiety proportion at M12 (27.8% vs. 46.2%, P = 0.050) were reduced in the reminiscence therapy group compared with those in the control care group. Moreover, the HADS for depression score declined at M9 (6.6 ± 2.0 vs. 7.5 ± 2.2, P = 0.025) and M12 (6.3 ± 2.3 vs. 7.7 ± 2.6, P = 0.005), but the proportion of those with depression was not different at each visit (P > 0.05) in the reminiscence therapy group compared with that of the control care group. In addition, the QLQ-C30 global health status score increased at M6 (71.3 ± 12.8 vs. 66.3 ± 12.9, P = 0.048) and M12 (74.5 ± 12.9 vs. 68.2 ± 13.3, P = 0.014) in the reminiscence therapy group compared to that in the control care group.ConclusionReminiscence therapy effectively mitigates anxiety and depression and improves the quality of life of elderly patients with HCC.

The social and environmental impacts of large dams are quantifiable and have been well documented, while small dams have often been presumed to be less environmentally damaging than large dams. The purpose of this study was to analyze longitudinal gradients in environmental, hydrodynamic variables and their impact on phytoplankton function, within a cascade of four reservoirs (XuanMiaoGuan, XMG; TianFuMiao, TFM; XiBeiKou, XBK; ShangJiaHe, SJH) and one reservoir bay (Huangbohe Bay, HBH), located from upstream to downstream in the Huangbo River, Hubei Province, China. Our results showed that water temperature, total nitrogen, and soluble silicate increased along the cascade reservoir system, while the concentration of dissolved oxygen and total phosphorus decreased. We identified 16 phytoplankton functional groups, and the predominant groups, including D (Synedra and Stephanodiscus hantzschii), E (Dinobryon divergens), Lo (Dinoflagellate: Peridinium bipes and Peridiniopsis), X2 (Chroomona), and Y (Cryptomonas), changed longitudinally from up to down in the cascade reservoirs. The number of dominant functional groups increased along the longitudinal gradient, indicating that the function of the phytoplankton community was more stable. Functional group D was the dominant phytoplankton functional group among the four reservoirs, and Lo group was dominant except SJH. The phytoplankton functional groups in the HBH have been completely changed due to the backwater jacking of the main stream of the Yangtze River. Euphotic depth, suspended solids, and nutrients were apparently the key factors driving variations in phytoplankton functional groups among the reservoirs. Notably, the patterns we observed were not all consistent with the cascading reservoir continuum concept (CRCC) that typically characterizes large rivers. Thus, our findings contribute to the further theoretical development of the CRCC, which may not apply widely to all cascade systems.

Regarding the composting of rural waste, numerous studies either addressed the composting of a single waste component or were conducted at a laboratory/pilot scale. However, far less is known about the mixed composting effect of multi-component rural waste on a large scale. Here, we examined nutrient transformation, maturity degree of decomposition, and succession of microbial communities in large-scale (1,000 kg mixed waste) compost of multi-component wastes previously optimized by response models. The results showed that multi-component compost can achieve the requirement of maturity and exhibit a higher nutritional value in actual compost. It is worth noting that the mixed compost effectively removed pathogenic fungi, in which almost no pathogenic fungi were detected, and only two pathogenic bacteria regrown in the cooling and maturation stages. Structural equation models revealed that the maturity (germination index and the ratio of ammonium to nitrate) of the product was directly influenced by compost properties (electrical conductivity, pH, total organic carbon, moisture, temperature, and total nitrogen) compared with enzymes (cellulase, urease, and polyphenol oxidase) and microbial communities. Moreover, higher contents of total phosphorus, nitrate-nitrogen, and total potassium were conducive to improving compost maturity, whereas relatively lower values of moisture and pH were more advantageous. In addition, compost properties manifested a remarkable indirect effect on maturity by affecting the fungal community (Penicillium and Mycothermus). Collectively, this evidence implies that mixed compost of multi-component rural waste is feasible, and its efficacy can be applied in practical applications. This study provides a solution for the comprehensive treatment and utilization of rural waste.

BackgroundPrescription errors impact the safety and efficacy of therapy and are considered to have a higher impact on paediatric populations. Nevertheless, information in paediatrics is still lacking, particularly in primary care settings. There exists a need to investigate the prevalence and characteristics of prescription errors in paediatric outpatients to prevent such errors during the prescription stage.MethodsA cross-sectional study to evaluate paediatric prescription errors in multi-primary care settings was conducted between August 2019 and July 2021. Prescriptions documented within the electronic pre-prescription system were automatically reviewed by the system and then, potentially inappropriate prescriptions would be reconciled by remote pharmacists via a regional pharmacy information exchange network. The demographics of paediatric patients, prescription details, and types/rates of errors were assessed and used to identify associated factors for prescription using logistic regression.ResultsA total of 39,754 outpatient paediatric prescriptions in 13 community health care centres were reviewed, among which 1,724 prescriptions (4.3%) were enrolled in the study as they met the inclusion criteria. Dose errors were the most prevalent (27%), with the predominance of underdosing (69%). They were followed by errors in selection without specified indications (24.5%), incompatibility (12.4%), and frequency errors (9.9%). Among critical errors were drug duplication (8.7%), contraindication (.9%), and drug interaction (.8%) that directly affect the drug's safety and efficacy. Notably, error rates were highest in medications for respiratory system drugs (50.5%), antibiotics (27.3%), and Chinese traditional medicine (12.3%). Results of logistic regression revealed that specific drug classification (antitussives, expectorants and mucolytic agents, anti-infective agents), patient age (

Introduction The cognitive dysfunction associated with nitrous oxide abuse is gradually becoming a major global public health concern. Despite the increasing prevalence of nitrous oxide abuse, there are currently no authorised/approved treatment options. Hyperbaric oxygen therapy (HBOT) has been proven to be an efficient method to improve cognitive function. The current randomised, double-blinded, placebo-controlled trial will explore the effect of HBOT on cognitive dysfunction induced by nitrous oxide abuse.Methods and analysis Eighty participants who abuse nitrous oxide and have cognitive dysfunction, including memory decline, disorientation, attention deficits, slower reactions and learning disabilities, will be included in the trial. They will be randomly assigned to receive either HBOT or sham-HBOT 90–120 min once daily for 5 days per week for 2 weeks. The primary outcome will be the improvement in the total score of the MATRICS Consensus Cognitive Battery, which will measure comprehensive cognitive function between the two groups. Additionally, attention will be measured by integrated visual and auditory continuous performance tests, executive function will be measured by the Wisconsin card sorting test, intelligence will be measured by Raven’s standard progressive matrices and cognitive control will be measured by the Stroop colour word interference test.Ethics and dissemination This protocol was approved by the West China Hospital of Sichuan University Biomedical Research Ethics Committee. The report of the study will be disseminated via scientific forums including peer-reviewed publications and presentations at national and international conferences.Trial registration number Chinese Clinical Trial Registry (ChiCTR2100047111).

In China, more than 47 million toilets in rural areas have been upgraded since the nationwide sanitation program, popularly referred to as the “toilet revolution,” was launched in 2015. However, little is currently known about the environmental risks of manure, or rural residents’ satisfaction. Here, we have selected 50 rural residents from 10 provinces and focused on two types of toilets to evaluate the environmental and social impacts of improving toilets in rural areas. The monitoring results showed that human excrement was mainly alkaline, and the concentrations of total nitrogen and phosphorus in the composting toilets ranged from 259.21 to 330.46 mg/kg and from 2.71 to 3.71 mg/kg, respectively, while their contents in septic tank effluents were generally 381.31–2040.84 mg/L and 10.41–80.46 mg/L, respectively. The pH and EC values exceeded the soil background value in individual regions, and the harmless effect of the two types of toilets did not fully meet the standard requirements, indicating that toilet manure, albeit possessed certain resource utilization potential, guard against the risk of pollution. Additionally, based on a fuzzy comprehensive evaluation model, it was found that the comprehensive evaluation score of Jiangsu Province is the highest, that of Gansu Province is the lowest, and the overall score is “high in the southeast and low in the northwest.” This study provides basic data and references for establishing a scientific and feasible evaluation system of rural toilet retrofitting and strengthens government guidance and training related to toilet retrofitting.

Considering the dispersion of the material properties and load,the collaborative analysis of the air-cooled turbine blade low-cycle fatigue reliability was done using the distributed collaborative response surface method. The deterministic analysis of the turbine blade was completed by the finite elements software. The total strain amplitude and mean stress response surface was established using the artificial neural network and the material life response surface using the linear hetero-variance regression method. The blade life response surface was established by collaborating with the two response surfaces. The low-cycle fatigue reliability analysis of the blade was completed using the Monte-Carlo method. Comparing with the traditional response surface method,the distributed collaborative response surface method is more accurate.

Image enhancement and restoration is among the most investigated topics in the field of underwater machine vision. The objective image quality assessment is a fundamental part of optimizing underwater enhancement and restoration technologies. However, most no-reference (NR) metrics are not specifically designed for underwater image quality assessment. Moreover, since the reference (undegraded) images are not available in underwater scenes, the classical full-reference (FR) metrics cannot be used to evaluate underwater image enhancement and restoration methods. In this paper, we first design an underwater image synthesis algorithm (UISA), in which depending on the real-world underwater image, we can produce a synthetic underwater image from an outdoor ground-truth image. Based on this strategy, we establish a new large-scale benchmark that contains ground-truth images and synthetic underwater images of the same scene, called synthetic underwater image dataset (SUID). Our SUID is constructed on the basis of the underwater image formation model (IFM) and characteristics of underwater optical propagation, possessing solid reliability and feasibility. The proposed SUID creates possibility for a FR evaluation of existing technologies for underwater image enhancement and restoration, which is illustrated by performing extensive experiments and quantitative analysis. The SUID is available online at: http://dx.doi.org/10.21227/agdr-y109.

Underwater captured images often suffer from poor visibility caused by two major degradations: scattering and absorption. In this paper, we propose a hybrid framework for underwater image enhancement, which unifies underwater white balance and variational contrast and saturation enhancement. In our framework, the improved underwater white balance (UWB) algorithm is integrated with histogram stretching, aiming to better compensate the attenuation difference along the propagation path and remove undesired color castings. In addition, a variational contrast and saturation enhancement (VCSE) model is developed based on the enhanced result obtained from UWB. The advantages of VCSE model lie in the improvements of contrast and saturation as well as the elimination of hazy appearance induced by scattering. Moreover, we design a fast Gaussian pyramid-based algorithm to speed up the solving of VCSE model. The improvements achieved by our method include the more effective in color correction, haze removal and detail clarification. Extensive qualitative and quantitative assessments demonstrate that the proposed approach obtains high quality outcomes, which outperforms several state-of-the-art methods. Application tests further verify the effectiveness and broad application prospects of our proposed method.

In an integrated energy distribution system (IEDS), an energy hub has been introduced and deemed to be a suitable tool for managing and integrating multi-party energy forms. Due to different energies having diverse characteristics and being coupled with each other, it is difficult for an energy hub to implement the optimal scheduling of multiple energy sources. Therefore, an energy optimization management model is proposed based on the Stackelberg game, which considers the exergy conversion of multi-party energy sources in different operation modes. The problem is solved by the two-layer distributed optimization algorithm, in which the energy hub acts as the leader and is followed by the users. Furthermore, in order to alleviate the deception, malicious tampering, subpeption, and other secure risks in energy trading, blockchain is introduced into the energy hub and the concept of exergy coin (EC) is proposed. A credit-based blockchain framework and concurrent block building consensus process is explored to reduce the calculation cost and promote the exergy trading efficiency. Finally, the case study shows how the proposed method can effectively optimize energy scheduling and configure a more reasonable energy solution.

Introduction Obstructive sleep apnoea (OSA) is a highly prevalent disease that causing systemic hypertension. Furthermore, altitude-dependent hypobaric hypoxic condition and Tibetan ethnicity have been associated with systemic hypertension independent of OSA, therefore patients with OSA living at high altitude might be at profound risk to develop systemic hypertension. Acetazolamide has been shown to decrease blood pressure, improve arterial oxygenation and prevent high altitude periodic breathing in healthy volunteers ascending to high altitude and decrease blood pressure in patients with systemic hypertension at low altitude. However, the effect of acetazolamide on 24-hour blood pressure, sleep-disordered disturbance and daytime cognitive performance in patients with OSA permanently living at high altitude has not been studied.Methods and analysis This study protocol describes a randomised, placebo-controlled, double-blinded crossover trial. Highland residents of both sexes, aged 30–60 years, Tibetan ethnicity, living at an elevation of 3650 m and apnoea–hypopnoea index over 15/hour will be included. Participants will be randomly assigned to a 2×2 week treatment period starting with 750 mg/day acetazolamide followed by placebo treatment or vice versa, separated by a 1-week wash-out phase. Clinical assessments, 24-hour ambulatory blood pressure monitoring (ABPM), polysomnography (PSG), near-infrared spectroscopy, nocturnal fluid shift and cognitive performance will be assessed before and at the end of each treatment period. The primary outcome will be the difference in 24-hour mean blood pressure between acetazolamide therapy and placebo; secondary outcomes will be the difference in other 24-hour ABPM-derived parameters, PSG-derived parameters, cognitive performance and overnight change in different segments of fluid volume between acetazolamide therapy and placebo. Accounting for potential dropouts, 40 participants will be recruited.Ethics and dissemination The protocol was approved by the West China Hospital of Sichuan University Biomedical Research Ethics Committee. Recruitment will start in spring 2022. Dissemination of the results include presentations at conferences and publications in peer-reviewed journals.Trial registration number ChiCTR2100049304.

Abstract Some plants with low fertility are morphologically intermediate between Roegneria stricta and Roegneria turczaninovii, and were suspected to be natural hybrids between these species. In this study, karyotype analysis showed that natural hybrids and their putative parents were tetraploids (2n = 4x = 28). Meiotic pairing in natural hybrids is more irregular than its putative parents. Results of genomic in situ hybridization and fluorescence in situ hybridization indicate that natural hybrids contain the same genome as their putative parents. The nuclear gene DNA meiotic recombinase 1 (DMC1) and the chloroplast gene rps16 of natural hybrids and their putative parents were analyzed for evidence of hybridization. The results from molecular data supported by morphology and cytology demonstrated that the plants represent natural hybrids between R. stricta and R. turczaninovii. The study is important for understanding species evolution in the genus since it demonstrates for the first time the existence of populations of natural homoploid hybrids in Roegneria. The study also reports for the first time that the composition of the genomic formula of R. turczaninovii is StY, confirming that the current taxonomic status is correct.

IL-21/IL-21R was documented to participate in the regulation of multiple infection and inflammation. During Chlamydia muridarum (C. muridarum) respiratory infection, our previous study had revealed that the absence of this signal induced enhanced resistance to infection with higher protective Th1/Th17 immune responses. Here, we use the murine model of C. muridarum respiratory infection and IL-21R deficient mice to further identify a novel role of IL-21/IL-21R in neutrophilic inflammation. Resistant IL-21R-/- mice showed impaired neutrophil recruitment to the site of infection. In the absence of IL-21/IL-21R, pulmonary neutrophils also exhibited reduced activation status, including lower CD64 expression, MPO activity, and neutrophil-produced protein production. These results correlated well with the decrease of neutrophil-related chemokines (KC and MIP-2), inflammatory cytokines (IL-6, IL-1β, and TNF-α), and TLR/MyD88 pathway mediators (TLR2, TLR4, and MyD88) in infected lungs of IL-21R-/- mice than normal mice. Complementarily, decreased pulmonary neutrophil infiltration, activity, and levels of neutrophilic chemotactic factors and TLR/MyD88 signal in infected lungs can be corrected by rIL-21 administration. These results revealed that IL-21/IL-21R may aggravate the neutrophil inflammation through regulating TLR/MyD88 signal pathway during chlamydial respiratory infection.

Chlamydia trachomatis usually causes mucosal infections, bringing considerable morbidity and socioeconomic burden worldwide. We previously revealed that IL-27/IL-27R mediates protection against chlamydial invasion by promoting a protective Th1 response and suppressing neutrophilic inflammation. Here, we used the mouse model of Chlamydia muridarum (C. muridarum) respiratory infections to further investigate the impact of IL-27 signaling in the DCs-regulated immune response, since an elevated IL-27/IL-27R expression in DCs was identified following chlamydial infection. An adoptive transfer of Chlamydia muridarum-stimulated DCs to wild-type mice approach was subsequently used, and the donor-DCs-promoted resistance with a higher Th1 response against chlamydial infection was attenuated when DCs lacking IL-27R were used as donor cells. Flow cytometry analysis revealed the suppression of IL-27 signaling on DCs phenotypic maturation. A further functional maturation analysis of DCs revealed that IL-27 signaling restricted the protein and mRNA expression of IL-10 from DCs following infection. Thus, these findings suggest that IL-27 signaling could support the Th1 response via inhibiting IL-10 production in DCs, thus mediating the protective host defense against chlamydial respiratory infection.