Portable one-step effervescence tablet-based microextraction combined with smartphone digital image colorimetry: Toward field and rapid detection of trace nickel ion.

In this study, the one-step switchable hydrophilic solvent (SHS)-based effervescence tablet microextraction (ETME) was coupled with smartphone digital image colorimetry (SDIC) for the field detection of nickel ion (Ni2+) for the first time. Both extractant and CO2 were generated in situ when the novel SHS-based effervescence tablet was placed in the sample solution. The complexant 1-(2-pyridinylazo)-2-naphthaleno (PAN) dissolved from the effervescence tablet to form a stable complex with Ni2+, and the extractant was uniformly dispersed in the sample solution under the action of CO2 and fully in contact with Ni-PAN, which enabled efficient extraction of Ni2+. The color changes of the extraction phase were captured by smartphone, then a quantitative relationship between the concentrations of Ni2+ and color intensity of images captured using a smartphone was established by customized applet WASDIC, which realized quantitative analysis of Ni2+ in different samples. Under optimal conditions, the enhancement factor (EF) of the proposed method was 65.1, the limit of detection (LOD) and limit of quantification (LOQ) were 1.69 and 5.64 µg L-1, respectively. The developed method was successfully applied to the detection of trace Ni2+ in the environmental samples and natural medicines. And the applicability of the method for use in field analysis was validated.

The S100 family is a prognostic biomarker and correlated with immune cell infiltration in pan-cancer.

BACKGROUND: The S100 protein family is a group of small molecular EF-hand calcium-binding proteins that play critical roles in various biological processes, including promotion of growth, metastasis and immune evasion of tumor. However, the potential roles of S100 protein family expression in tumor microenvironment (TME) cell infiltration in pan-cancer remain elusive. METHODS: Herein, we conducted a comprehensive assessment of the expression patterns of the S100 protein family in pan-cancer, meticulously examining their correlation with characteristics of TME cell infiltration. The S100 score was constructed to quantify S100 family expression patterns of individual tumors. RESULTS: The S100 family was a potent risk factor in many cancers. Clustering analysis based on the transcriptome patterns of S100 protein family identified two cancer clusters with distinct immunophenotypes and clinical characteristics. Cluster A, with lower S100 expression, exhibited lower immune infiltration, whereas, Cluster B, with higher S100 expression, featured higher immune infiltration. Interestingly, Cluster B had a poorer prognosis, likely due to an immune-excluded phenotype resulting from stromal activation. The analysis revealed robust enrichment of the TGFb and EMT pathways in the cohort exhibiting high S100 score, alongside a positive correlation between the S100 score and Treg levels, suggesting the manifestation of an immune-excluded phenotype in this group. Moreover, S100 families were associated with the prognosis of 22 different cancers and a noteworthy association was observed between high S100 score and an unfavorable response to anti-PD-1/L1 immunotherapy. Consistent findings across two independent immunotherapy cohorts substantiated the advantageous therapeutic outcomes and clinical benefits in patients displaying lower S100score. CONCLUSION: Our analysis demonstrated the role of S100 family in formation of TME diversity and complexity, enabling deeper cognition of TME infiltration characterization and the development of personalized immunotherapy strategies targeting S100 family for unique tumor types.

Correlation between anti-müllerian hormone in polycystic ovarian syndrome with metformin: a systematic review and meta-analysis.

OBJECTIVE: This study aims to examine the short-term effects of oral metformin (MET) on serum anti-müllerian hormone (AMH) levels and to verify its impact on AMH concentrations in women with polycystic ovary syndrome (PCOS). METHODS: The literature search, extending from January 2000 to April 2023, was conducted using databases such as PubMed, Embase, and the Cochrane Central, resulting in the inclusion of 20 studies. These selected studies, evaluated for quality using the Newcastle-Ottawa Scale, investigated changes in AMH levels before and after treatment, with durations ranging from less than three months to over six months. The reported outcomes were quantified as standardized mean differences (SMD) with 95% confidence intervals (CI). This comprehensive systematic review and meta-analysis was registered with the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42023420705. The statistical analyses were performed using Review Manager 5.4.1. RESULTS: ① The study incorporated 20 articles, consisting of 12 prospective studies, 7 randomized controlled trials (RCT), and 1 cross-sectional study. ② Serum AMH levels in patients with PCOS diminish subsequent to the oral administration of MET. ③ Across the spectrum of studies analyzed, a pronounced degree of heterogeneity is evident, potentially ascribed to differential parameters including body mass index (BMI), daily pharmacological dosages, the temporal extent of treatment regimens, criteria of PCOS, and detection Methods. ④ The impact of MET on AMH levels exhibits a dose-responsive trend, with escalating doses of MET being associated with progressively greater declines in AMH concentrations in the patient population. ⑤ For women with PCOS receiving MET therapy, a minimum treatment duration of three months may be necessary to observe a reduction in serum AMH levels. CONCLUSIONS: The results of this meta-analysis indicate that MET treatment exerts a suppressive effect on serum AMH levels in women with PCOS. It appears that a treatment duration of at least three months is required to achieve a significant decrease in AMH concentrations. Furthermore, the influence of MET on AMH is dose-dependent, with higher doses correlating with more pronounced reductions in AMH levels among the patients studied.

Lin28 affects the proliferation and osteogenic differentiation of human dental pulp stem cells by directly inhibiting let-7b maturation.

OBJECTIVE: Activation of Lin28 gene under certain conditions promotes tissue damage repair. However, it remains unknown whether conditional expression of Lin28 facilitates the recovery of damaged pulp tissue. In the study, we focus on exploring the effects and possible regulatory mechanisms of Lin28 on the proliferation and differentiation of human dental pulp stem cells (hDPSCs). MATERIALS AND METHODS: We adopted techniques such as the ethynyl-2'-deoxyuridine (EdU) incorporation assay, RNA-protein immunoprecipitation (RIP) analysis, and luciferase assays to study the regulation of hDPSCs by Lin28. Furthermore, gain-of-function and loss-of-function analyses were also used in explored factors regulating hDPSCs activation. RESULTS: The results show that Lin28 inhibited osteogenic differentiation by directly targets pre-let-7b. Through bioinformatics sequencing and dual luciferase experiments we learned that let-7b directly targets the IGF2BP2 3'UTR. Silencing of IGF2BP2 showed a similar biological effect as overexpression of let-7b. Overexpression of IGF2BP2 counteracted the differentiation-promoting effects produced by let-7b overexpression. DISCUSSION/CONCLUSIONS: In conclusion, the RNA-binding protein Lin28 regulates osteogenic differentiation of hDPSCs by inhibiting let-7 miRNA maturation. And mature let-7b directly regulated the expression of IGF2BP2 by targeting the 3'UTR region of IGF2BP2 mRNA thus further inhibiting the differentiation of hDPSCs.

A comprehensive review on the inherent and enhanced antifouling mechanisms of hydrogels and their applications.

Biofouling remains a persistent challenge within the domains of biomedicine, tissue engineering, marine industry, and membrane separation processes. Multifunctional hydrogels have garnered substantial attention due to their complex three-dimensional architecture, hydrophilicity, biocompatibility, and flexibility. These hydrogels have shown notable advances across various engineering disciplines. The antifouling efficacy of hydrogels typically covers a range of strategies to mitigate or inhibit the adhesion of particulate matter, biological entities, or extraneous pollutants onto their external or internal surfaces. This review provides a comprehensive review of the antifouling properties and applications of hydrogels. We first focus on elucidating the fundamental principles for the inherent resistance of hydrogels to fouling. This is followed by a comprehensive investigation of the methods employed to enhance the antifouling properties enabled by the hydrogels' composition, network structure, conductivity, photothermal properties, release of reactive oxygen species (ROS), and incorporation of silicon and fluorine compounds. Additionally, we explore the emerging prospects of antifouling hydrogels to alleviate the severe challenges posed by surface contamination, membrane separation and wound dressings. The inclusion of detailed mechanistic insights and the judicious selection of antifouling hydrogels are geared toward identifying extant gaps that must be bridged to meet practical requisites while concurrently addressing long-term antifouling applications.

Innovative freeze-drying technique in the fabrication of dissolving microneedle patch: Enhancing transdermal drug delivery efficiency.

Microneedle patch (MNP) has become a hot research topic in the field of transdermal drug delivery due to its ability to overcome the stratum corneum barrier. Among the various types of microneedles, dissolving microneedles represent one of the most promising transdermal delivery methods. However, the most used method for preparing dissolving microneedles, namely microfabrication, suffers from issues such as long drying time, susceptibility to humidity, and large batch-to-batch variability, which limit the development of dissolving microneedles. In this study, we report for the first time a method for preparing dissolving microneedles using freeze-drying technology. We screened substrates suitable for freeze-dried microneedle patch (FD-MNP) and used coating technology to enhance the mechanical strength of FD-MNP, allowing them to meet the requirements for skin penetration. We successfully prepared FD-MNP using hyaluronic acid as the substrate and insulin as the model drug. Scanning electron microscopy revealed that the microneedles had a porous structure. After coating, the mechanical strength of the microneedles was 0.61 N/Needle, and skin penetration rate was 97%, with a penetration depth of 215 µm. The tips of the FD-MNP dissolved completely within approximately 60 s after skin penetration, which is much faster than conventional MNP (180 s). In vitro transdermal experiments showed that the FD-MNP shortened the lag time for transdermal delivery of rhodamine 123 and insulin compared to conventional MNP, indicating a faster transdermal delivery rate. Pharmacological experiments showed that the FD-MNP lowered mouse blood glucose levels more effectively than conventional MNP, with a relative pharmacological availability of 96.59 ± 2.84%, higher than that of conventional MNP (84.34 ± 3.87%), P = 0.0095. After storage under 40℃ for two months, the insulin content within the FD-MNP remained high at 95.27 ± 4.46%, which was much higher than that of conventional MNP (58.73 ± 3.71%), P < 0.0001. In conclusion, freeze-drying technology is a highly valuable method for preparing dissolving microneedles with potential applications in transdermal drug delivery.

Investigation of natural deep eutectic solvent for the extraction of crude polysaccharide from Polygonatum kingianum and influence of metal elements on its immunomodulatory effects.

In this study, natural deep eutectic solvent (NADES) was used to extract Polygonatum kingianum crude polysaccharide (PKCP) and response surface methodology (RSM) was designed to optimize the extraction procedure. The immunomodulatory effect of PKCP and the influence of metal elements on its immunomodulatory effect were further discussed. The optimum conditions for PKCP extraction were obtained by RSM optimization: NADES were synthesized with a 1:2 choline chloride-glycerol molar ratio, then extracted at a liquid-solid ratio of 16.6 mL g-1 and water content of 31.2 % for 60 min at 60 °C. This method was used for the extraction of PKCP, and the extraction efficiency was 29.69 %, which was 2.5 times greater than the conventional method of water extraction. In the concentration range of 200-800 µg mL-1, PKCP could activate macrophages, promoting NO secretion and mRNA expression of interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS) in a dose-dependent way. NO secretion and cytokine expression were not affected when the metal elements were spiked to the equivalent of the metal elements contained in Polygonatum kingianum. When the content of metal elements was higher, the secretion of NO and the gene expression of iNOS were both decreased, which may affect the immunomodulatory effect of Polygonatum kingianum.

Tactile stimulation promotes the recovery of motor function in rats with cerebral ischaemia.

OBJECTIVES: Tactile stimulation (TS) can promote neurogenesis and motor function recovery in rats with hypoxic-ischaemic brain injury, but the underlying mechanism is not clear. This study aimed to assess the effects of TS on neurological function in rats after cerebral ischaemia and explore the underlying mechanism. METHODS: Adult SD rats were randomly divided into a sham operation (SHAM) group, middle cerebral artery occlusion with tactile stimulation (TS-MCAO) group and middle cerebral artery occlusion with sedentary intervention (SED-MCAO) group. Twenty-four hours after MCAO, rats in the TS-MCAO group received TS for 20 min/d 5 d/w for 4 weeks. Cerebral blood flow (CBF), changes in body weight, behavioural scores, the infarct volume, corticospinal tract integrity, and neurochemical changes were measured, and Golgi-Cox staining, transmission electron microscopy and Western blotting were performed. RESULTS: CBF recovery was improved in the TS-MCAO group compared with the SED-MCAO group. Body weight and behavioural scores in the TS-MCAO group significantly changed after 28 days of intervention. After 14 and 28 days of intervention, the infarct volume decreased significantly, the ratios of fractional anisotropy increased and the ratios of apparent diffusion coefficient decreased, the ratios of Nacetylaspartate (NAA)/creatine (Cr) and glutamate (Glu)/ Cr increased. After 28 days of intervention, the complexity and density of dendrites, the number of synapses and the expression of synaptic plasticity-related proteins increased in the peri-infarct cortex. CONCLUSION: TS can improve motor performance in rats with cerebral ischaemia and the improvement is correlated with synaptic plasticity. This finding would be helpful to provide a rehabilitation program for patients following stroke.

A novel deep eutectic solvent modified magnetic covalent organic framework for the selective separation and determination of trace copper ion in medicinal plants and environmental samples.

BACKGROUND: Pretreatment techniques should be introduced before metal ion determination because there is very low content of heavy metals in Chinese medicinal plants and environmental samples. Magnetic dispersive micro solid phase extraction (MDMSPE) has been widely used for the separation and adsorption of heavy metal pollutants in medicinal plants and environmental samples. However, the majority of MDMSPE adsorbents have certain drawbacks, including low selectivity, poor anti-interference ability, and small adsorption capacity. Therefore, modifying currently available adsorption materials has gained attention in research. RESULTS: In this study, a novel adsorbent MCOF-DES based on a magnetic covalent organic framework (MCOF) modified by a new deep eutectic solvent (DES) was synthesized for the first time and used as an adsorbent of MDMSPE. The MDMSPE was combined with inductively coupled plasma optical emission spectrometry (ICP-OES) for selective separation, enrichment, and accurate determination of trace copper ion (Cu2+) in medicinal plants and environmental samples. Various characterization results show the successful preparation of new MCOF-DES. Under the optimal conditions, the enrichment factor (EF) of Cu2+ was 30, the limit of detection (LOD) was 0.16 µg L-1, and the limit of quantitation (LOQ) was 0.54 µg L-1. The results for the determination of Cu2+ were highly consistent with those of inductively coupled plasma mass spectrometry (ICP-MS), which verified the accuracy and reliability of the method. SIGNIFICANCE: The established method based on a new adsorption material MCOF-DES has achieved the selective separation and determination of trace Cu2+ in medicinal and edible homologous medicinal materials (Phyllanthus emblica Linn.) and environmental samples (soil and water), which provides a promising, selective, and sensitive approach for the determination of trace Cu2+ in other real samples.

Brain microvascular endothelial cell-derived exosomes transmitting circ_0000495 promote microglial M1-polarization and endothelial cell injury under hypoxia condition.

Human brain microvascular endothelial cells (HBMVECs) and microglia play critical roles in regulating cerebral homeostasis during ischemic stroke. However, the role of HBMVECs-derived exosomes in microglia polarization after stroke remains unknown. We isolated exosomes (Exos) from oxygen glucose deprivation (OGD)-exposed HBMVECs, before added them into microglia. Microglia polarization markers were tested using RT-qPCR or flow cytometry. Inflammatory cytokines were measured with ELISA. Endothelial cell damage was assessed by cell viability, apoptosis, apoptosis-related proteins, oxidative stress, and angiogenic activity using CCK-8, flow cytometry, western blot, ELISA, and endothelial tube formation assay, respectively. We also established middle cerebral artery occlusion (MCAO) mice model to examine the function of circ_0000495 on stroke in vivo. Our study found that HBMVECs-Exos reduced M2 markers (IL-10, CD163, and CD206), increased M1 markers (TNF-α, IL-1ß, and IL-12), CD86-positive cells, and inflammatory cytokines (TNF-α and IL-1ß), indicating the promotion of microglial M1-polarization. Microglial M1-polarization induced by HBMVECs-Exos reduced viability and promoted apoptosis and oxidative stress, revealing the aggravation of endothelial cell damage. However, circ_0000495 silencing inhibited HBMVECs-Exos-induced alterations. Mechanistically, circ_0000495 adsorbed miR-579-3p to upregulate toll-like receptor 4 (TLR4) in microglia; miR-579-3p suppressed HBMVECs-Exos-induced alterations via declining TLR4; furthermore, Yin Yang 1 (YY1) transcriptionally activated circ_0000495 in HBMVECs. Importantly, circ_0000495 aggravated ischemic brain injury in vivo via activating TLR4/nuclear factor-κB (NF-κB) pathway. Collectively, OGD-treated HBMVECs-Exos transmitted circ_0000495 to regulate miR-579-3p/TLR4/NF-κB axis in microglia, thereby facilitating microglial M1-polarization and endothelial cell damage.

Forebrain excitatory neuron-specific loss of Brpf1 attenuates excitatory synaptic transmission and impairs spatial and fear memory.

Bromodomain and plant homeodomain (PHD) finger containing protein 1 (Brpf1) is an activator and scaffold protein of a multiunit complex that includes other components involving lysine acetyltransferase (KAT) 6A/6B/7. Brpf1, KAT6A, and KAT6B mutations were identified as the causal genes of neurodevelopmental disorders leading to intellectual disability. Our previous work revealed strong and specific expression of Brpf1 in both the postnatal and adult forebrain, especially the hippocampus, which has essential roles in learning and memory. Here, we hypothesized that Brpf1 plays critical roles in the function of forebrain excitatory neurons, and that its deficiency leads to learning and memory deficits. To test this, we knocked out Brpf1 in forebrain excitatory neurons using CaMKIIa-Cre. We found that Brpf1 deficiency reduced the frequency of miniature excitatory postsynaptic currents and downregulated the expression of genes Pcdhgb1, Slc16a7, Robo3, and Rho, which are related to neural development, synapse function, and memory, thereby damaging spatial and fear memory in mice. These findings help explain the mechanisms of intellectual impairment in patients with BRPF1 mutation.

Impact of quantitative safety targets on road fatality reduction: an empirical support toward governance plan.

Introduction: The role of quantitative target setting has become an important topic in debates on the improvement of road safety performance. Specifically, there are questions regarding the relationship between quantitative safety targets and their actual effects. Although previous studies have provided important insights into this subject, their empirical findings have largely been equivocal, and research on this topic remains inadequate. Methods: Based on panel data representing 20 years of observations from 34 OECD member states, we employed nonlinear and linear panel models to investigate whether and how the attributes of quantitative road safety targets (i.e., target ambition and duration) influence their success (i.e., target completion status and rate). Results: The results indicate that a quantitative target with a higher level of ambition is associated with a lower likelihood and rate of completion, whereas there is no support for a connection between target duration and final completion rate. This suggests that an excessively ambitious target does not necessarily result in better road safety performance and is detrimental to achieving expected fatality reductions. Conclusion: From an empirical perspective, this study revealed a potential interaction effect between quantitative road safety targets and practical fatality reduction performance, providing government officials and policymakers with essential references for future practices on target setting and governance planning in regard to public health.

Tissue-specific knockout in Drosophila neuromuscular system reveals ESCRT's role in formation of synapse-derived extracellular vesicles.

Tissue-specific gene knockout by CRISPR/Cas9 is a powerful approach for characterizing gene functions in animal development. However, this approach has been successfully applied in only a small number of Drosophila tissues. The Drosophila motor nervous system is an excellent model system for studying the biology of neuromuscular junction (NMJ). To expand tissue-specific CRISPR to the Drosophila motor system, here we present a CRISPR-mediated tissue-restricted mutagenesis (CRISPR-TRiM) toolkit for knocking out genes in motoneurons, muscles, and glial cells. We validated the efficacy of this toolkit by knocking out known genes in each tissue, demonstrated its orthogonal use with the Gal4/UAS binary expression system, and showed simultaneous knockout of multiple redundant genes. Using these tools, we discovered an essential role for SNARE pathways in NMJ maintenance. Furthermore, we demonstrate that the canonical ESCRT pathway suppresses NMJ bouton growth by downregulating the retrograde Gbb signaling. Lastly, we found that axon termini of motoneurons rely on ESCRT-mediated intra-axonal membrane trafficking to lease extracellular vesicles at the NMJ.

Novel Coumarin Derivatives Inhibit the Quorum Sensing System and Iron Homeostasis as Antibacterial Synergists against Pseudomonas aeruginosa.

Pseudomonas aeruginosa (P. aeruginosa) is well-known to cause biofilm-associated drug resistance and infections that often lead to treatment failure. Herein, we reported a dual-acting antibiofilm strategy by inhibiting both the bacterial quorum sensing system and the iron uptake system. A series of coumarin derivatives were synthesized and evaluated, and compound 4t was identified as the most effective biofilm inhibitor (IC50 = 3.6 µM). Further mechanistic studies have confirmed that 4t not only inhibits the QS systems but also competes strongly with pyoverdine as an iron chelator, causing an iron deficiency in P. aeruginosa. Additionally, 4t significantly improved the synergistic antibacterial effects of ciprofloxacin and tobramycin by more than 200-1000-fold compared to the single-dose antibiotic treatments. Therefore, our study has shown that 4t is a potentially novel antibacterial synergist candidate to treat bacterial infections.

Colossal magnetoresistance in the multiple wave vector charge density wave regime of an antiferromagnetic Dirac semimetal.

Colossal negative magnetoresistance is a well-known phenomenon, notably observed in hole-doped ferromagnetic manganites. It remains a major research topic due to its potential in technological applications. In contrast, topological semimetals show large but positive magnetoresistance, originated from the high-mobility charge carriers. Here, we show that in the highly electron-doped region, the Dirac semimetal CeSbTe demonstrates similar properties as the manganites. CeSb0.11Te1.90 hosts multiple charge density wave modulation vectors and has a complex magnetic phase diagram. We confirm that this compound is an antiferromagnetic Dirac semimetal. Despite having a metallic Fermi surface, the electronic transport properties are semiconductor-like and deviate from known theoretical models. An external magnetic field induces a semiconductor metal-like transition, which results in a colossal negative magnetoresistance. Moreover, signatures of the coupling between the charge density wave and a spin modulation are observed in resistivity. This spin modulation also produces a giant anomalous Hall response.

A hierarchical porous aerohydrogel for enhanced water evaporation.

Natural solar-powered steam generation provides a promising strategy to deal with deteriorating water resources. However, the practical applications of this strategy are limited by the tedious manufacturing of structures at micro-nano levels to concentrate heat and transport water to heat-localized regions. Herein, this work reports the fabrication of hierarchically porous aerohydrogel with enhanced light absorption and thermal localization at the air-solid interface. This aerohydrogel steam generator is fabricated by a simple yet controllable micropore generation approach to assemble air and hydrogel into hierarchically porous gas-solid hybrids. The tunable micropore size in a wide range from 99±49µm to 316±58µm not only enables contrasting sunlight absorptance (0.2 - 2.5µm) by reducing the reflection of solar light but also harnesses water transportation to the heating region via a capillary force-driven liquid flow. Therefore, a solar-vapor conversion efficiency of 91.3% under one sun irradiation was achieved using this aerohydrogel evaporator, reaching a ready evaporation rate of 2.76kg m-2 h-1 and 3.71kg m-2 h-1 under one and two sun irradiations, respectively. Our work provides a versatile and scalable approach to engineering porous hydrogels for highly efficient steam generation and opens an avenue for other potential practical applications based on this aerohydrogel.

Genetic diversity and population structure of Polygonatum cyrtonema Hua in China using SSR markers.

Polygonatum cyrtonema Hua is a perennial herbaceous plant of the Polygonatum genus, belonging to the Liliaceae family, with significant medicinal and nutritional value. In China, this species is a traditional medicinal and edible herb with a long history of application and is widely appreciated by the people. However, as the demand for medicinal herbs continues to grow, excessive harvesting has led to the depletion of wild resources and the risk of genetic erosion. In addition, the chaotic cultivation of varieties and the lack of high quality germplasm resources have led to inconsistent quality of medical materials. Therefore, it is urgent to conduct genetic diversity evaluation of this species and establish a sound conservation plan. This study assessed the genetic diversity and population structure of 96 samples collected from seven regions in China using the simple sequence repeat (SSR) molecular marker technology. In this study, a total of 60 alleles (Na) were detected across the 10 polymorphic SSR markers used, with an average of 6.0 alleles generated per locus. The values of polymorphic information content (PIC) values ranged from 0.3396 to 0.8794, with an average value of 0.6430. The average value of the effective number of alleles (Ne) was 2.761, and the average value of the Shannon's information index (I) was 1.196. The population structure analysis indicates that the Polygonatum cyrtonema Hua germplasm can be classified into three subpopulations (JZ, QY, JD) at the molecular level, which corresponds to the previous subgroups identified based on individual plant phenotypic traits. Analysis of Molecular Variance (AMOVA) showed that 74% of the genetic variation was between individuals within populations in different regions. The phylogenetic analysis of the 96 germplasm samples divided them into three main populations. The QY and JD subpopulations are largely clustered together, which could be attributed to their mountainous distribution and the local climate environment. The genetic differentiation coefficient (Fst) value was low at 0.065, indicating relatively low population differentiation. The ratio of the genetic differentiation coefficient (Fst) between the JZ population and the other two populations (QY and JD) is much higher than the ratio between the QY and JD populations. Based on the clustering results and the ratio of the genetic differentiation coefficient (Fst), it can be inferred that the genetic relationship between the QY and JD subpopulations is closer, with a certain degree of genetic differentiation from the JZ subpopulation. This study supports the conservation of germplasm resources of Polygonatum cyrtonema Hua in China and provides new parental material for germplasm genetic improvement and breeding programs.

Design, Synthesis, and Antifungal Activities of Novel Carboxamides Derivatives Bearing a Chalcone Scaffold as Potential SDHIs.

In search for SDHIs fungicides, twenty-five novel carboxamides containing a chalcone scaffold were designed, synthesized, and evaluated for antifungal activities against five pathogenic fungi. The results showed that compound 5 k exhibited outstanding antifungal activity against R. solani with an EC50 value of 0.20 µg/mL, which was much better than that of commercial SDHIs Boscalid (EC50 =0.74 µg/mL). Moreover, compound 5 k also displayed promising antifungal activities against S. sclerotiorum, B. cinerea, and A. alternate (IC50 =2.53-4.06 µg/mL), indicating that 5 k had broad-spectrum antifungal activity. Additionally, in vivo antifungal activities results showed that 5 k could significantly inhibit the growth of R. solani in rice leaves with good protective efficacy (57.78 %) and curative efficacy (58.45 %) at 100 µg/mL, both of which were much better than those of Boscalid, indicating a promising application prospect. Moreover, SEM analysis showed that compound 5 k could remarkably disrupt the typical structure and morphology of R. solani hyphae. Further SDH enzyme inhibition assay and molecular docking study revealed that lead compound 5 k had a similar mechanism of action as commercial SDHI Boscalid. These results indicated that compound 5 k showed potential as a SDHIs fungicide and deserved further investigation.

LAMP2A, LAMP2B and LAMP2C: similar structures, divergent roles.

LAMP2 (lysosomal associated membrane protein 2) is one of the major protein components of the lysosomal membrane. There currently exist three LAMP2 isoforms, LAMP2A, LAMP2B and LAMP2C, and they vary in distribution and function. LAMP2A serves as a receptor and channel for transporting cytosolic proteins in a process called chaperone-mediated autophagy (CMA). LAMP2B is required for autophagosome-lysosome fusion in cardiomyocytes and is one of the components of exosome membranes. LAMP2C is primarily implicated in a novel type of autophagy in which nucleic acids are taken up into lysosomes for degradation. In this review, the current evidence for the function of each LAMP2 isoform in various pathophysiological processes and human diseases, as well as their possible mechanisms, are comprehensively summarized. We discuss the evolutionary patterns of the three isoforms in vertebrates and provide technical guidance on investigating these isoforms. We are also concerned with the newly arising questions in this particular research area that remain unanswered. Advances in the functions of the three LAMP2 isoforms will uncover new links between lysosomal dysfunction, autophagy and human diseases.Abbreviation: ACSL4: acyl-CoA synthetase long-chain family member 4; AD: Alzheimer disease; Ag: antigens; APP: amyloid beta precursor protein; ATG14: autophagy related 14; AVSF: autophagic vacuoles with unique sarcolemmal features; BBC3/PUMA: BCL2 binding component 3; CCD: C-terminal coiled coil domain; CMA: chaperone-mediated autophagy; CVDs: cardiovascular diseases; DDIT4/REDD1: DNA damage inducible transcript 4; ECs: endothelial cells; ER: endoplasmic reticulum; ESCs: embryonic stem cells; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GBA/ß-glucocerebrosidase: glucosylceramidase beta; GSCs: glioblastoma stem cells; HCC: hepatocellular carcinoma; HD: Huntington disease; HSCs: hematopoietic stem cells; HSPA8/HSC70: heat shock protein family A (Hsp70) member 8; IL3: interleukin 3; IR: ischemia-reperfusion; LAMP2: lysosomal associated membrane protein 2; LDs: lipid droplets; LRRK2: leucine rich repeat kinase 2; MA: macroautophagy; MHC: major histocompatibility complex; MST1: macrophage stimulating 1; NAFLD: nonalcoholic fatty liver disease; NFE2L2/NRF2: NFE2 like bZIP transcription factor 2; NLRP3: NLR family pyrin domain containing 3; PARK7: Parkinsonism associated deglycase; PD: Parkinson disease; PEA15/PED: proliferation and apoptosis adaptor protein 15; PKM/PKM2: pyruvate kinase M1/2; RA: rheumatoid arthritis; RARA: retinoic acid receptor alpha; RCAN1: regulator of calcineurin 1; RCC: renal cell carcinoma; RDA: RNautophagy and DNautophagy; RNAi: RNA interference; RND3: Rho Family GTPase 3; SG-NOS3/eNOS: deleterious glutathionylated NOS3; SLE: systemic lupus erythematosus; TAMs: tumor-associated macrophages; TME: tumor microenvironment; UCHL1: ubiquitin C-terminal hydrolase L1; VAMP8: vesicle associated membrane protein 8.

Diagnostic performance of magnetic resonance imaging-based machine learning in Alzheimer's disease detection: a meta-analysis.

PURPOSE: Advanced machine learning (ML) algorithms can assist rapid medical image recognition and realize automatic, efficient, noninvasive, and convenient diagnosis. We aim to further evaluate the diagnostic performance of ML to distinguish patients with probable Alzheimer's disease (AD) from normal older adults based on structural magnetic resonance imaging (MRI). METHODS: The Medline, Embase, and Cochrane Library databases were searched for relevant literature published up until July 2021. We used the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool and Checklist for Artificial Intelligence in Medical Imaging (CLAIM) to evaluate all included studies' quality and potential bias. Random-effects models were used to calculate pooled sensitivity and specificity, and the Deeks' test was used to assess publication bias. RESULTS: We included 24 models based on different brain features extracted by ML algorithms in 19 papers. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curve for ML in detecting AD were 0.85 (95%CI 0.81-0.89), 0.88 (95%CI 0.84-0.91), 7.15 (95%CI 5.40-9.47), 0.17 (95%CI 0.12-0.22), 43.34 (95%CI 26.89-69.84), and 0.93 (95%CI 0.91-0.95). CONCLUSION: ML using structural MRI data performed well in diagnosing probable AD patients and normal elderly. However, more high-quality, large-scale prospective studies are needed to further enhance the reliability and generalizability of ML for clinical applications before it can be introduced into clinical practice.