Characterization and discrimination of the taste and aroma of Tibetan Qingke baijiu using electronic tongue, electronic nose and gas chromatography-mass spectrometry.

Consumers rely on flavor characteristics to distinguish different types of Qingke Baijiu (QKBJ). Clarifying QKBJ's traits enhances its recognition and long-term growth. Thus, this study analyzed eight QKBJ samples from different regions of Tibet (Lhasa, Sannan, Shigatse, and Qamdo) using GC-MS, electronic nose and electronic tongue. The radar charts of the electronic tongue and electronic nose revealed highly similar profiles for all eight samples. Fifteen common compounds were found in all samples, with the main alcohol compounds being 3-Methyl-1-butanol, 1-hexanol, isobutanol, 1-butanol, 1-nonanol, and phenylethyl alcohol, imparting fruity, floral, and herbal aromas. However, the Sannan samples had higher total alcohol content than total ester content, emphasizing bitterness. Lhasa1 exhibited the most prominent sweetness, Lhasa2 the most noticeable sourness, and Qamdo the most pronounced umami. Lhasa3 and Lhasa4 had total acid content second only to total ester content. Tyd had the highest alkanes, while Lhasa had most aldehydes among samples.

Exploiting tertiary lymphoid structures gene signature to evaluate tumor microenvironment infiltration and immunotherapy response in colorectal cancer.

Background: Tertiary lymphoid structures (TLS) is a particular component of tumor microenvironment (TME). However, its biological mechanisms in colorectal cancer (CRC) have not yet been understood. We desired to reveal the TLS gene signature in CRC and evaluate its role in prognosis and immunotherapy response. Methods: The data was sourced from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Based on TLS-related genes (TRGs), the TLS related subclusters were identified through unsupervised clustering. The TME between subclusters were evaluated by CIBERSORT and xCell. Subsequently, developing a risk model and conducting external validation. Integrating risk score and clinical characteristics to create a comprehensive nomogram. Further analyses were conducted to screen TLS-related hub genes and explore the relationship between hub genes, TME, and biological processes, using random forest analysis, enrichment and variation analysis, and competing endogenous RNA (ceRNA) network analysis. Multiple immunofluorescence (mIF) and immunohistochemistry (IHC) were employed to characterize the existence of TLS and the expression of hub gene. Results: Two subclusters that enriched or depleted in TLS were identified. The two subclusters had distinct prognoses, clinical characteristics, and tumor immune infiltration. We established a TLS-related prognostic risk model including 14 genes and validated its predictive power in two external datasets. The model's AUC values for 1-, 3-, and 5-year overall survival (OS) were 0.704, 0.737, and 0.746. The low-risk group had a superior survival rate, more abundant infiltration of immune cells, lower tumor immune dysfunction and exclusion (TIDE) score, and exhibited better immunotherapy efficacy. In addition, we selected the top important features within the model: VSIG4, SELL and PRRX1. Enrichment analysis showed that the hub genes significantly affected signaling pathways related to TLS and tumor progression. The ceRNA network: PRRX1-miRNA (hsa-miR-20a-5p, hsa-miR-485-5p) -lncRNA has been discovered. Finally, IHC and mIF results confirmed that the expression level of PRRX1 was markedly elevated in the TLS- CRC group. Conclusion: We conducted a study to thoroughly describe TLS gene signature in CRC. The TLS-related risk model was applicable for prognostic prediction and assessment of immunotherapy efficacy. The TLS-hub gene PRRX1, which had the potential to function as an immunomodulatory factor of TLS, could be a therapeutic target for CRC.

Population-wide impact of a pragmatic program to identify and manage individuals at high-risk of cardiovascular disease: a cluster randomized trial in 120 villages from Northern China.

Objectives: To explore the population-wide impacts of an evidence-based high-risk strategy for prevention of cardiovascular diseases in resource-poor populations. Methods: A cluster randomized controlled trial was conducted among 120 villages in rural China, with 60 on intervention and 60 on usual care as controls, for 2 years. The intervention emphasized training village doctors to identify high-risk individuals and administering standardized treatments focusing on hypertension management. A random sample of 20 men aged ≥50 years and 20 women aged ≥60 years was drawn from each village before randomization for the baseline survey, and another independent random sample with the same age and sex distribution was drawn at 2 years for the post-intervention survey. The primary outcome was the population mean systolic blood pressure (SBP). Secondary outcomes included the proportions of patients who received regular primary care, antihypertensive medications, aspirin, or lifestyle advice. Results: A total of 5,654 high cardiovascular risk individuals were identified and managed by village doctors in intervention villages for 15 months on average, with mean SBP lowered by 19.8 mmHg and the proportion with blood pressure under control increased from 22.1% to 72.7%. The primary analysis of the two independent samples (5,050 and 4,887 participants each) showed that population-wide mean SBP in intervention villages did not differ from that in control villages at 2 years (mean difference = 1.0 mmHg, 95% CI: -2.19, 4.26; P = 0.528), though almost all secondary outcomes concerning primary care indicators significantly increased in intervention villages. Conclusions: In our study, the pragmatic cardiovascular risk management program targeting on high-risk individuals significantly improved the quality of primary care. However, its impact on population blood pressure level and the burden of hypertension-related diseases appeared very limited. Clinical Trial Registration: ClinicalTrial.gov identifier, NCT01259700.

Research Advances in the Roles of N6-Methyladenosine Modification in Ovarian Cancer.

Ovarian cancer (OC) is the most lethal gynecological tumor, characterized by its insidious and frequently recurring metastatic progression. Owing to limited early screening methods, over 70% of OC cases are diagnosed at advanced stages, typically stage III or IV. Recently, N6-methyladenosine (m6A) modification has emerged as a hotspot of epigenetic research, representing a significant endogenous RNA modification in higher eukaryotes. Numerous studies have reported that m6A-related regulatory factors play pivotal roles in tumor development through diverse mechanisms. Moreover, recent studies have indicated the aberrant expression of multiple regulatory factors in OC. Therefore, this paper comprehensively reviews research advancements concerning m6A in OC, aiming to elucidate the regulatory mechanism of m6A-associated regulators on pivotal aspects, such as proliferation, invasion, metastasis, and drug resistance, in OC. Furthermore, it discusses the potential of m6A-associated regulators as early diagnostic markers and therapeutic targets, thus contributing to the diagnosis and treatment of OC.

Ovarian cancer (OC) presents a formidable challenge in the medical field, often detected at advanced stages, necessitating urgent exploration of diagnostic and therapeutic avenues. This review delves into the intricate role of N6-methyladenosine (m6A) RNA modification in OC, a dynamic epigenetic process increasingly recognized for its regulatory role in cancer biology. Highlighting recent advancements, the review sheds light on how m6A-related factors influence crucial aspects of OC progression, including tumor growth, metastasis, and resistance to treatment. Specifically, m6A methyltransferases, binding proteins, and demethylases exert multifaceted effects on OC progression, influencing the expression of pivotal oncogenes and tumor suppressors. While promising, translating these insights into effective therapies requires further investigation. By comprehensively understanding the influence of m6A on OC, there lies hope for developing improved diagnostic techniques and novel treatment strategies to combat this complex disease.

M6A-mediated hsa_circ_0061179 inhibits DNA damage in ovarian cancer cells via miR-143-3p/TIMELESS.

Ovarian cancer (OC) is among the most common and deadly solid malignancies in women. Despite many advances in OC research, the incidence of OC continues to rise, and its pathogenesis remains largely unknown. Herein, we elucidated the function of hsa_circ_0061179 in OC. The levels of hsa_circ_0061179, miR-143-3p, TIMELESS, and DNA damage repair-related proteins in OC or normal ovarian tissues and cells were measured using real-time quantitative polymerase chain reaction and immunoblotting. The biological effects of hsa_circ_0061179 and miR-143-3p on proliferation, clone formation, DNA damage, and apoptosis of OC cells were detected by the cell counting kit-8 assay, 5-methylethyl-2'-deoxyuridine, flow cytometry, the comet assay, and immunofluorescence staining combined with the confocal microscopy. The interaction among hsa_circ_0061179, miR-143-3p, and TIMELESS was validated by the luciferase reporter assay. Mice tumor xenograft models were used to evaluate the influence of hsa_circ_0061179 on OC growth in vivo. We found that human OC biospecimens expressed higher levels of hsa_circ_0061179 and lower levels of miR-143-3p. Hsa_circ_0061179 was found to bind with miR-143-3p, which directly targets TIMELESS. Hsa_circ_0061179 knockdown or miR-143-3p overexpression suppressed the proliferation and clone formation of OC cells and increased DNA damage and apoptosis of OC cells via the miR-143-3p/TIMELESS axis. Furthermore, we demonstrated that METTL3 could direct the formation of has_circ_0061179 through a specific m6A modification site. YTHDC1 facilitated the cytoplasmic transfer of has_circ_0061179 by directly binding to the modified m6A site. Our findings suggest that hsa_circ_0061179 acts as the sponge of miR-143-3p to activate TIMELESS signaling and inhibits DNA damage and apoptosis in OC cells.

Nitrogen-doped carbon dots as fluorescent probes for sensitive and selective determination of Fe3.

At present, the contamination of water resources by heavy metal ions has posed a significant threat to human survival. Therefore, it is particularly critical to develop low-cost, easy-to-use, and highly efficient heavy metal detection technologies. In this work, a fast and cost-effective fluorescent probe for nitrogen-doped carbon dots (N-CDs) was prepared using one-step hydrothermal method with citric acid (CA) as carbon source, and melamine as nitrogen source. The structural and optical characterizations of the resulting N-CDs were investigated in details. The results showed that the quantum yield of the prepared fluorescent probe was as high as 45 %, and an average fluorescence lifetime was about 7.80 ns. N-CDs have excellent water solubility and dispersibility, with an average size of 2.58 nm. N-CDs exhibited excellent specific responsiveness to Fe3+ and can be used as an effective method for detecting Fe3+ at low-concentrations (the concentrations of N-CDs as low as 0.24 µg/mL) using fluorescent probes. The linear response of the fluorescent probe N-CDs to Fe3+ was formed in the concentration range of 20-80 µM, and the detection limit was 3.18 µM. In addition, in the actual water samples analysis, the recovery rate reached 97.05-100.58 %. The prepared of N-CDs provide available Fe3+ fluorescent probes in the environment.

Study of association of leptin with leukocyte telomere length in a Chinese rural population.

BACKGROUND: Previous studies have demonstrated the relationship between adipocyte factors, insulin resistance, and other indicators with telomere length. However, these studies did not consider the influence of changes in different indicators on telomere length over time. Therefore, the aim of this study is to elucidate the impact of changes in adipocyte factors, HOMA-IR, and other indicators on the dynamic variation of telomere length. METHODS: The data were from a cohort study conducted in Ningxia, China. A total of 1624 subjects were analyzed. Adipokines and relative leukocyte telomere length (RLTL) were measured, and changes in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), Homeostatic Model Assessment for ß-Cell Function (HOMA-ß), and Quantitative Insulin Sensitivity Check Index (QUICKI) were calculated. Generalized linear models evaluated associations between changes in adipokines and RLTL changes. Furthermore, univariate analyses examined the effects of changes in adipokines and insulin resistance indicators on ΔRLTL. RESULTS: The research findings indicate that females generally have shorter telomeres compared to males. In comparison to the low-level group of Δleptin (LEP), the high-level group of ΔLEP shows a negative correlation with ΔRLTL (B=-1.32, 95% CI (-2.38, -0.27)). Even after multivariable adjustments, this relationship persists (B=-1.31, 95% CI (-2.24, -0.23)). Further analysis reveals that after adjusting for ΔHOMA-IR, ΔHOMA-ß, and ΔQUICKI, the high-level group of ΔLEP still exhibits a significant negative correlation with ΔRLTL (B=-1.37, 95% CI (-2.43, -0.31)). However, the interaction effects between ΔHOMA-IR, ΔHOMA-ß, ΔQUICKI, and ΔLEP do not affect ΔRLTL. CONCLUSIONS: Elevated levels of leptin were significantly correlated with shortened telomere length. This suggests that increased leptin levels may impact overall individual health by affecting telomere length, underscoring the importance of measures to reduce leptin levels to mitigate the onset and progression of related diseases.

Punicalagin attenuates hyperuricemia via restoring hyperuricemia-induced renal and intestinal dysfunctions.

INTRODUCTION: It is estimated that 90% of hyperuricemia cases are attributed to the inability to excrete uric acid (UA). The two main organs in charge of excreting UA are the kidney (70%) and intestine (30%). Previous studies have reported that punicalagin (PU) could protect against kidney and intestinal damages, which makes it a potential candidate for alleviating hyperuricemia. However, the effects and deeper action mechanisms of PU for managing hyperuricemia are still unknown. OBJECTIVE: To investigate the effect and action mechanisms of PU for ameliorating hyperuricemia. METHODS: The effects and action mechanisms of PU on hyperuricemia were assessed using a hyperuricemia mice model. Phenotypic parameters, metabolomics analysis, and 16S rRNA sequencing were applied to explore the effect and fundamental action mechanisms inside the kidney and intestine of PU for improving hyperuricemia. RESULTS: PU administration significantly decreased elevated serum uric acid (SUA) levels in hyperuricemia mice, and effectively alleviated the kidney and intestinal damage caused by hyperuricemia. In the kidney, PU down-regulated the expression of UA resorption protein URAT1 and GLUT9, while up-regulating the expression of UA excretion protein ABCG2 and OAT1 as mediated via the activation of MAKP/NF-κB in hyperuricemia mice. Additionally, PU attenuated renal glycometabolism disorder, which contributed to improving kidney dysfunction and inflammation. Similarly, PU increased UA excretion protein expression via inhibiting MAKP/NF-κB activation in the intestine of hyperuricemia mice. Furthermore, PU restored gut microbiota dysbiosis in hyperuricemia mice. CONCLUSION: This research revealed the ameliorating impacts of PU on hyperuricemia by restoring kidney and intestine damage in hyperuricemia mice, and to be considered for the development of nutraceuticals used as UA-lowering agent.

RNA three-dimensional structure drives the sequence organization of potato spindle tuber viroid quasispecies.

RNA viruses and viroids exist and evolve as quasispecies due to error-prone replication. Quasispecies consist of a few dominant master sequences alongside numerous variants that contribute to genetic diversity. Upon environmental changes, certain variants within quasispecies have the potential to become the dominant sequences, leading to the emergence of novel infectious strains. However, the emergence of new infectious variants remains unpredictable. Using mutant pools prepared by saturation mutagenesis of selected stem and loop regions, our study of potato spindle tuber viroid (PSTVd) demonstrates that mutants forming local three-dimensional (3D) structures similar to the wild type (WT) are more likely to accumulate in PSTVd quasispecies. The selection mechanisms underlying this biased accumulation are likely associated with cell-to-cell movement and long-distance trafficking. Moreover, certain trafficking-defective PSTVd mutants can be spread by functional sister genomes in the quasispecies. Our study reveals that the RNA 3D structure of stems and loops constrains the evolution of viroid quasispecies. Mutants with a structure similar to WT have a higher likelihood of being maintained within the quasispecies and can potentially give rise to novel infectious variants. These findings emphasize the potential of targeting RNA 3D structure as a more robust approach to defend against viroid infections.

Fe-based cyclically catalyzing double free radical nanogenerator for tumor-targeted chemodynamic therapy.

The prosperity of chemodynamic therapy provides a new strategy for tumor treatment. However, the lack of reactive oxygen species and the specific reductive tumor microenvironment have limited the further development of chemodynamic therapy. Herein, we reported a Fe-based cyclically catalyzing double free radical system for tumor therapy by catalyzing exogenous potassium persulfate (K2S2O8) and endogenous hydrogen peroxide (H2O2). Sufficient amounts of Fe3+ and S2O82- were delivered to tumor sites via tumor-targeted hyaluronic acid (HA) encapsulated mesoporous silica nanoparticles (MSNs) and released under the dual stimulation of acid and hyaluronidase (HAase) in the tumor microenvironment. Fe3+ was reduced to Fe2+ by the reducing agents of loaded tannic acid (TA) and intracellular glutathione (GSH), and Fe2+ was subsequently reacted with S2O82- and endogenous H2O2 to produce two types of ROS (˙OH and SO4-˙), showing an excellent anti-tumor effect. This process not only supplied Fe2+ for the catalysis of active substances, but also reduced the concentration of reduced substances in cells, which was conducive to the existence of free radicals for the efficient killing of tumor cells. Therefore, this iron-based catalysis of exogenous and exogenous active substances to realize a dual-radical oncotherapy nanosystem would provide a new perspective for chemodynamic therapy.

Light3DHS: A lightweight 3D hippocampus segmentation method using multiscale convolution attention and vision transformer.

The morphological analysis and volume measurement of the hippocampus are crucial to the study of many brain diseases. Therefore, an accurate hippocampal segmentation method is beneficial for the development of clinical research in brain diseases. U-Net and its variants have become prevalent in hippocampus segmentation of Magnetic Resonance Imaging (MRI) due to their effectiveness, and the architecture based on Transformer has also received some attention. However, some existing methods focus too much on the shape and volume of the hippocampus rather than its spatial information, and the extracted information is independent of each other, ignoring the correlation between local and global features. In addition, many methods cannot be effectively applied to practical medical image segmentation due to many parameters and high computational complexity. To this end, we combined the advantages of CNNs and ViTs (Vision Transformer) and proposed a simple and lightweight model: Light3DHS for the segmentation of the 3D hippocampus. In order to obtain richer local contextual features, the encoder first utilizes a multi-scale convolutional attention module (MCA) to learn the spatial information of the hippocampus. Considering the importance of local features and global semantics for 3D segmentation, we used a lightweight ViT to learn high-level features of scale invariance and further fuse local-to-global representation. To evaluate the effectiveness of encoder feature representation, we designed three decoders of different complexity to generate segmentation maps. Experiments on three common hippocampal datasets demonstrate that the network achieves more accurate hippocampus segmentation with fewer parameters. Light3DHS performs better than other state-of-the-art algorithms.

Feeding Appropriate Nutrients during the Adult Stage to Promote the Growth and Development of Carposina sasakii Offspring.

Nutrients consumed during the adult stage are a key factor affecting the growth, development, and reproduction of insect offspring and thus could play an important role in insect population research. However, there is absence of conclusive evidence regarding the direct effects of parental (F0) nutritional status on offspring (F1) fitness in insects. Carposina sasakii Matsumura is a serious, widespread fruit-boring pest that negatively impacts orchards and the agricultural economy across East Asia. In this study, life history data of F1 directly descended from F0C. sasakii fed with seven different nutrients (water as control, 5 g·L-1 honey solution, 10 g·L-1 honey solution, 5 g·L-1 sucrose solution, 10 g·L-1 sucrose solution, 15 g·L-1 sucrose solution, and 20 g·L-1 sucrose solution) were collected under laboratory conditions. The growth and development indices, age-stage specific survival rate, age-stage specific fecundity, age-stage specific life expectancy, age-stage specific reproductive value, and population parameters of these offspring were analyzed according to the age-stage, two-sex life table theory. The results showed that the nutritional status of F0 differentially affects the growth, development, and reproduction of F1. The F1 offspring of F0 adult C. sasakii fed with 10 g·L-1 sucrose had significantly higher life table parameters than those of other treatments (intrinsic rate of increase, r = 0.0615 ± 0.0076; finite rate of increase, λ = 1.0634 ± 0.0081; net reproductive rate, R0 = 12.61 ± 3.57); thus, 10 g·L-1 sucrose was more suitable for raising C. sasakii in the laboratory than other treatments. This study not only provides clear evidence for the implications of altering F0 nutritional conditions on the fitness of F1 in insects, but also lays the foundation for the implementation of feeding technologies within the context of a well-conceived laboratory rearing strategy for C. sasakii.

Arbuscular Mycorrhizal Fungi-Mediated Modulation of Physiological, Biochemical, and Secondary Metabolite Responses in Hemp (Cannabis sativa L.) under Salt and Drought Stress.

The increasing impact of global climate change has resulted in adversity stresses, like salt and drought, gradually becoming the main factors that limit crop growth. Hemp, which contains numerous medicinal active components and multiple bioactive functions, is widely used in the agricultural, industrial, and medical fields, hence promoting the rapid development of related industries. Arbuscular mycorrhizal fungi (AMF) can establish a symbiotic relationship with 80% of vascular plants. This symbiosis promotes host plant growth, regulates plant physiology and biochemistry, facilitates secondary metabolite synthesis, and enhances resistance to abiotic stresses. However, the effects of salt stress, drought stress, and AMF interaction in hemp are not well understood. In this study, to investigate this, we performed a study where we cultured hemp that was either inoculated or uninoculated with Funneliformis mosseae and determined changes in effective colonization rate, growth, soluble substances, photosynthesis, fluorescence, ions, and secondary metabolites by cultivating hemp under different concentrations of NaCl (0 mM, 100 mM, and 200 mM) and different soil moisture content (45%, 25%, and 15%). The results showed that salt, drought stress, or salt-drought interaction stress all inhibited colonization rate after stress, plant growth, mainly due to ion toxicity and oxidative damage. Inoculation with F. mosseae effectively alleviated plant growth inhibition under 100 mM NaCl salt stress, drought stress, and salt-drought interaction stress conditions. It also improved osmoregulation, photosynthetic properties, fluorescence properties, and ion homeostasis, and promoted the accumulation of secondary metabolites. However, under 200 mM NaCl salt stress conditions, inoculation with F. mosseae negatively affected plant physiology, biochemistry, and secondary metabolite synthesis, although it did alleviate growth inhibition. The results demonstrate that there are different effects of salt-drought interaction stress versus single stress (salt or drought stress) on plant growth physiology. In addition, we provide new insights about the positive effects of AMF on host plants under such stress conditions and the effects of AMF on plants under high salt stress.

Viroid Replication, Movement, and the Host Factors Involved.

Viroids represent distinctive infectious agents composed solely of short, single-stranded, circular RNA molecules. In contrast to viruses, viroids do not encode for proteins and lack a protective coat protein. Despite their apparent simplicity, viroids have the capacity to induce diseases in plants. Currently, extensive research is being conducted on the replication cycle of viroids within both the Pospiviroidae and Avsunviroidae families, shedding light on the intricacies of the associated host factors. Utilizing the potato spindle tuber viroid as a model, investigations into the RNA structural motifs involved in viroid trafficking between different cell types have been thorough. Nevertheless, our understanding of the host factors responsible for the intra- and inter-cellular movement of viroids remains highly incomplete. This review consolidates our current knowledge of viroid replication and movement within both families, emphasizing the structural basis required and the identified host factors involved. Additionally, we explore potential host factors that may mediate the intra- and inter-cellular movement of viroids, addressing gaps in our understanding. Moreover, the potential application of viroids and the emergence of novel viroid-like cellular parasites are also discussed.

Ca2LaTaO6:Bi3+/Mn4+ Phosphors with High Brightness Far-Red Emitting and Luminescence Enhancement for Plant Growth LED Lights and Temperature Sensor.

Herein, Bi3+/Mn4+ doped Ca2LaTaO6 phosphors with a double-perovskite structure were successfully synthesized with solid-state reaction at high temperature. The photoluminescence (PL) performances were investigated in detail. The blue radiation (∼465 nm) from the Bi3+ ion and the red radiation (∼686 nm) originating from the Mn4+ ion were obtained under 313 nm excitation. Especially, the pathway of energy transfer (Bi3+ → Mn4+) contributes to enhance the red emission intensity (Mn4+: ∼686 nm) in Ca2LaTaO6:Bi3+/Mn4+ system. The PL mechanism of Ca2LaTaO6:Bi3+/Mn4+ was analyzed through luminescence lifetimes and PL spectra. Moreover, the emitting bands of Ca2LaTaO6:Bi3+/Mn4+ were primarily matched with the absorbing bands of carotenoids and phytochrome PFR on behalf of plant growth, so the phosphors were suitable for the design of a plant growth light under near-ultraviolet to blue excitation. At last, the optical temperature dependent performances of the Ca2LaTaO6:Bi3+/Mn4+ were analyzed with luminescence intensity ratio technology. The sample has presented excellent temperature measuring relative sensitivity (SR = 2.106% K-1). The results illustrated that the Ca2LaTaO6:Bi3+/Mn4+ phosphor also can be used to develop an optical temperature sensor.

Association between dietary antioxidant capacity and type 2 diabetes mellitus in Chinese adults: a population-based cross-sectional study.

BACKGROUND: Higher intakes of dietary antioxidants have been linked to a lower type 2 diabetes mellitus (T2DM) risk. However, few studies have comprehensively examined the overall dietary antioxidant capacity, assessed by dietary antioxidant quality scores (DAQS) and dietary total antioxidant capacity (DTAC), related to T2DM risk, especially in populations consuming relatively monotonous diets. This study aimed to evaluate the associations of DAQS, DTAC, and T2DM among rural Chinese adults. METHODS: Data from 12,467 participants from the Natural Population Cohort of Northwest China: Ningxia Project was analyzed. Dietary intake was assessed using a validated semi-quantitative food frequency questionnaire. DAQS were calculated based on vitamins A, C, and E, zinc (Zn), and selenium (Se) intake. DTAC was estimated using the ferric-reducing ability of plasma assay. Logistic regression models were used to evaluate the associations of DAQS and DTAC with T2DM risk. Restricted cubic splines were used to assess potential non-linear relationships between DTAC and T2DM. RESULTS: T2DM was observed in 1,238 (9.9%) participants. After adjusting for confounders, compared to the lowest tertiles (T1) of DAQS, the odds ratios (ORs) for T2DM were 1.03 (95% CI 0.82-1.30) in T2 and 0.85 (95% CI 0.68-1.06) in T3 (P = 0.010). Compared to T1, the ORs for T2DM in the highest T3 were 0.78 (95% CI 0.67-0.91, P-trend = 0.008) for vitamin A, 1.34 (95% CI 1.15-1.56, P-trend < 0.001) for vitamin E, 0.83 (95% CI 0.71-0.97, P-trend = 0.007) for Se, and 0.86 (95% CI 0.74-1.01, P-trend = 0.033) for Zn. Compared to the lowest quartile(Q1) of DTAC, the OR in the highest Q4 was 0.96 (95% CI 0.80-1.17, P-trend = 0.024) for T2DM. A non-linear relationship was observed between DATC and T2DM. CONCLUSION: Higher DAQS and DATC were associated with a lower T2DM risk, suggesting that consuming antioxidant-rich foods may reduce the T2DM risk.

Knockout of SlDCL2b attenuates the resistance of tomato to potato spindle tuber viroid infection.

RNA interference, or RNA silencing, is an important defence mechanism against viroid infection in plants. Plants encode multiple DICER-LIKE (DCL) proteins that are key components of the RNA silencing pathway. However, the roles of different DCLs in defence responses against viroid infection remain unclear. Here, we determined the function of tomato DCL2b (SlDCL2b) in defence responses against potato spindle tuber viroid (PSTVd) infection using SlDCL2b loss-of-function tomato mutant plants. Compared with wild-type plants, mutant plants were more susceptible to PSTVd infection, developing more severe symptoms earlier and accumulating higher levels of PSTVd RNAs. Moreover, we verified the feedback mechanism for the regulation of SlDCL2b expression by miR6026. Functional blocking of tomato miR6026, by expressing its target mimics, can enhance resistance to PSTVd infection in tomato plants. These findings deepen the current understanding of RNAi-based resistance against viroid infection and provide a potentially new strategy for viroid control.

Neuromuscular organoids model spinal neuromuscular pathologies in C9orf72 amyotrophic lateral sclerosis.

Hexanucleotide repeat expansions in the C9orf72 gene are the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Due to the lack of trunk neuromuscular organoids (NMOs) from ALS patients' induced pluripotent stem cells (iPSCs), an organoid system was missing to model the trunk spinal neuromuscular neurodegeneration. With the C9orf72 ALS patient-derived iPSCs and isogenic controls, we used an NMO system containing trunk spinal cord neural and peripheral muscular tissues to show that the ALS NMOs could model peripheral defects in ALS, including contraction weakness, neural denervation, and loss of Schwann cells. The neurons and astrocytes in ALS NMOs manifested the RNA foci and dipeptide repeat proteins. Acute treatment with the unfolded protein response inhibitor GSK2606414 increased the glutamatergic muscular contraction 2-fold and reduced the dipeptide repeat protein aggregation and autophagy. This study provides an organoid system for spinal neuromuscular pathologies in ALS and its application for drug testing.

Machine Learning Accelerates De Novo Design of Antimicrobial Peptides.

Efficient and precise design of antimicrobial peptides (AMPs) is of great importance in the field of AMP development. Computing provides opportunities for peptide de novo design. In the present investigation, a new machine learning-based AMP prediction model, AP_Sin, was trained using 1160 AMP sequences and 1160 non-AMP sequences. The results showed that AP_Sin correctly classified 94.61% of AMPs on a comprehensive dataset, outperforming the mainstream and open-source models (Antimicrobial Peptide Scanner vr.2, iAMPpred and AMPlify) and being effective in identifying AMPs. In addition, a peptide sequence generator, AP_Gen, was devised based on the concept of recombining dominant amino acids and dipeptide compositions. After inputting the parameters of the 71 tridecapeptides from antimicrobial peptides database (APD3) into AP_Gen, a tridecapeptide bank consisting of de novo designed 17,496 tridecapeptide sequences were randomly generated, from which 2675 candidate AMP sequences were identified by AP_Sin. Chemical synthesis was performed on 180 randomly selected candidate AMP sequences, of which 18 showed high antimicrobial activities against a wide range of the tested pathogenic microorganisms, and 16 of which had a minimal inhibitory concentration of less than 10 µg/mL against at least one of the tested pathogenic microorganisms. The method established in this research accelerates the discovery of valuable candidate AMPs and provides a novel approach for de novo design of antimicrobial peptides.