miR-193b-3p and miR-346 Exert Antihypertensive Effects in the Rostral Ventrolateral Medulla.

BACKGROUND: Rostral ventrolateral medulla (RVLM) neuron hyperactivity raises sympathetic outflow, causing hypertension. MicroRNAs (miRNAs) contribute to diverse biological processes, but their influence on RVLM neuronal excitability and blood pressure (BP) remains widely unexplored. METHODS AND RESULTS: The RVLM miRNA profiles in spontaneously hypertensive rats were unveiled using RNA sequencing. Potential effects of these miRNAs in reducing neuronal excitability and BP and underlying mechanisms were investigated through various experiments. Six hundred thirty-seven miRNAs were identified, and reduced levels of miR-193b-3p and miR-346 were observed in the RVLM of spontaneously hypertensive rats. Increased miR-193b-3p and miR-346 expression in RVLM lowered neuronal excitability, sympathetic outflow, and BP in spontaneously hypertensive rats. In contrast, suppressing miR-193b-3p and miR-346 expression in RVLM increased neuronal excitability, sympathetic outflow, and BP in Wistar Kyoto and Sprague-Dawley rats. Cdc42 guanine nucleotide exchange factor (Arhgef9) was recognized as a target of miR-193b-3p. Overexpressing miR-193b-3p caused an evident decrease in Arhgef9 expression, resulting in the inhibition of neuronal apoptosis. By contrast, its downregulation produced the opposite effects. Importantly, the decrease in neuronal excitability, sympathetic outflow, and BP observed in spontaneously hypertensive rats due to miR-193b-3p overexpression was greatly counteracted by Arhgef9 upregulation. CONCLUSIONS: miR-193b-3p and miR-346 are newly identified factors in RVLM that hinder hypertension progression, and the miR-193b-3p/Arhgef9/apoptosis pathway presents a potential mechanism, highlighting the potential of targeting miRNAs for hypertension prevention.

Quorum sensing mediated response mechanism of anammox consortia to anionic surfactant: Molecular simulation and molecular evidence.

The widespread use of surfactants raise challenges to biological wastewater treatment. Anaerobic ammonium oxidation (anammox) process has the potential to treat wastewater containing anionic surfactants, but the response of anammox consortia at the molecular level under long-term exposure is unclear. Using high-throughput sequencing and gene quantification, combined with molecular docking, the effect of sodium dodecyl sulfonate (SDS) on anammox consortia were investigated. Levels of reactive oxygen species (ROS) might be lower than the threshold of oxidative damage, while the increase of lactate dehydrogenase (LDH) represented the cell membrane damage. Decreased abundance of functional genes (hdh, hzsA and nirS) indicated the decrease of the anammox bacterial abundance. Trace amounts of N-acyl homoserine lactone (AHL, C6-HSL, C8-HSL and C12-HSL) contained in influent could induce endogenous quorum sensing (QS), which could regulate the correlation between functional bacteria to optimize the microbial community and strengthen the resistance of anammox consortia to SDS. In addition, the proliferation of disinfectant resistance genes might increase the environmental pathogenicity of sewage discharge. This work highlights the potential response mechanism of anammox consortium to surfactants and provides a universal microbial-friendly bioenhancement strategy based on QS.

Bioinformatics gene analysis for potential biomarkers and therapeutic targets of Parkinson's disease based on neutrophil extracellular traps.

Introduction: Neutrophil extracellular traps (NETs) provide key innate immune mechanisms, and studies have shown innate immunity and adaptive immunity are directly linked to Parkinson's disease (PD) pathology. However, limited research has been conducted on NETs in the context of PD. Methods: A differential analysis was implemented to acquire differentially expressed genes (DEGs) between PD and control as well as between high- and low-score groups determined by a gene set variation analysis (GSVA). Then, the genes within the critical module, obtained through a weighted gene co-expression network analysis (WGCNA), were intersected with the DEGs to identify the overlapping genes. Then, five kinds of algorithms in the protein-protein interaction (PPI) were performed to identify potential biomarkers. Subsequently, a nomogram for forecasting PD probability was created. An enrichment analysis and an immune infiltration analysis were performed on the identified biomarkers. qRT-PCR was performed to validate the expression trends of three biomarkers. Results: We revealed 798 DEGs between PD and control groups as well as 168 DEGs between high- and low-score groups obtained by differential analyses. The pink module containing 926 genes was identified as the critical module. According to the intersection of these gene sets, a total of 43 overlapping genes were screened out. Furthermore, GPR78, CADM3, and CACNA1E were confirmed as biomarkers. Moreover, we found that biomarkers mainly participated in pathways, such as the 'hydrogen peroxide catabolic process', and 'cell cycle'; five kinds of differential immune cells between PD and control groups were identified. Finally, the qRT-PCR analysis demonstrated the up-regulation of GPR78, CADM3, and CACNA1E in the PD group. Discussion: Our study authenticated GPR78, CADM3, and CACNA1E as the biomarkers associated with PD. These findings provide an original reference for the diagnosis and treatment of PD.

Effectiveness of Targeted Nursing Measures to Relieve Swollen Limb Pain after Extremity Fracture.

Objective: The objective of this study is to evaluate the effectiveness of targeted nursing measures in relieving swollen limb pain after extremity fractures. The term "targeted nursing measures" refers to specific nursing interventions and care strategies that are designed to address the issue of swollen limb pain in patients with extremity fractures. Methods: Patients with extremity fractures treated in our hospital between January 2020 and December 2021 were recruited for eligibility assessment, and 100 patients were eventually included and assigned alternately at the time of admission to receive routine care, namely standard nursing interventions commonly provided to individuals with extremity fractures (These interventions included preoperative assessment, vital sign monitoring, postoperative status monitoring, local ice application, elevation of the affected limb, functional exercise, pain relief measures, postoperative nutrition, medication administration, and general health instruction) (routine group) or targeted care, namely care measures tailored to address swollen limb pain. (These targeted care measures included health education regarding the causes of limb fractures, precautions, causes of swollen limb pain after fractures, and treatment methods, decongestion care, ice compresses to promote vasoconstriction and reduce pain and swelling, psychological counseling to relieve negative emotions, and targeted rehabilitation training supervision) (targeted group), with 50 patients in each group. Outcome measures included swelling, pain, emotional state, and nursing satisfaction. Results: Targeted care resulted in better mitigation of swelling versus routine care (P < .05). Patients with targeted care had significantly lower visual analog scale (VAS) scores, self-rating anxiety scale (SAS) scores, and Hamilton depression scale (HAMD) scores, and higher Connor-Davidson resilience scale (CD-RISC) scores versus those with routine care (P < .05). Targeted care was associated with significantly higher nursing satisfaction versus routine care (P < .05). Conclusion: Targeted care rapidly relieves the degree of swelling and pain of patients with extremity fractures and ameliorates their emotional state, thereby promoting health recovery and effectively improving patient satisfaction.

Development and validation of a nomogram to predicting the efficacy of PD-1/PD-L1 inhibitors in patients with nasopharyngeal carcinoma.

PURPOSE: With the treatment of nasopharyngeal carcinoma (NPC) by PD-1/PD-L1 inhibitors used widely in clinic, it becomes very necessary to anticipate whether patients would benefit from it. We aimed to develop a nomogram to evaluate the efficacy of anti-PD-1/PD-L1 in NPC patients. METHODS: Totally 160 NPC patients were enrolled in the study. Patients were measured before the first PD-1/PD-L1 inhibitors treatment and after 8-12 weeks of immunotherapy by radiological examinations to estimate the effect. The least absolute shrinkage and selection operator (LASSO) logistic regression was used to screen hematological markers and establish a predictive model. The nomogram was internally validated by bootstrap resampling and externally validated. Performance of the model was evaluated using concordance index, calibration curve, decision curve analysis and receiver operation characteristic curve. RESULTS: Patients involved were randomly split into training cohort ang validation cohort. Based on Lasso logistic regression, systemic immune-inflammation index (SII) and ALT to AST ratio (LSR) were selected to establish a predictive model. The C-index of training cohort and validating cohort was 0.745 and 0.760. The calibration curves and decision curves showed the precise predictive ability of this nomogram. The benefit of the model showed in decision curve was better than TNM stage. The area under the curve (AUC) value of training cohort and validation cohort was 0.745 and 0.878, respectively. CONCLUSION: The predictive model helped evaluating efficacy with high accuracy in NPC patients treated with PD-1/PD-L1 inhibitors.

Circulating tumor cells shielded with extracellular vesicle-derived CD45 evade T cell attack to enable metastasis.

Circulating tumor cells (CTCs) are precursors of distant metastasis in a subset of cancer patients. A better understanding of CTCs heterogeneity and how these CTCs survive during hematogenous dissemination could lay the foundation for therapeutic prevention of cancer metastasis. It remains elusive how CTCs evade immune surveillance and elimination by immune cells. In this study, we unequivocally identified a subpopulation of CTCs shielded with extracellular vesicle (EVs)-derived CD45 (termed as CD45+ CTCs) that resisted T cell attack. A higher percentage of CD45+ CTCs was found to be closely correlated with higher incidence of metastasis and worse prognosis in cancer patients. Moreover, CD45+ tumor cells orchestrated an immunosuppressive milieu and CD45+ CTCs exhibited remarkably stronger metastatic potential than CD45- CTCs in vivo. Mechanistically, CD45 expressing on tumor surfaces was shown to form intercellular CD45-CD45 homophilic interactions with CD45 on T cells, thereby preventing CD45 exclusion from TCR-pMHC synapse and leading to diminished TCR signaling transduction and suppressed immune response. Together, these results pointed to an underappreciated capability of EVs-derived CD45-dressed CTCs in immune evasion and metastasis, providing a rationale for targeting EVs-derived CD45 internalization by CTCs to prevent cancer metastasis.

SGLT2-independent effects of canagliflozin on NHE3 and mitochondrial complex I activity inhibit proximal tubule fluid transport and albumin uptake.

Beyond glycemic control, SGLT2 inhibitors (SGLT2is) have protective effects on cardiorenal function. Renoprotection has been suggested to involve inhibition of NHE3 leading to reduced ATP-dependent tubular workload and mitochondrial oxygen consumption. NHE3 activity is also important for regulation of endosomal pH, but the effects of SGLT2i on endocytosis are unknown. We used a highly differentiated cell culture model of proximal tubule (PT) cells to determine the direct effects of SGLT2i on Na+-dependent fluid transport and endocytic uptake in this nephron segment. Strikingly, canagliflozin but not empagliflozin reduced fluid transport across cell monolayers and dramatically inhibited endocytic uptake of albumin. These effects were independent of glucose and occurred at clinically relevant concentrations of drug. Canagliflozin acutely inhibited surface NHE3 activity, consistent with a direct effect, but did not affect endosomal pH or NHE3 phosphorylation. In addition, canagliflozin rapidly and selectively inhibited mitochondrial complex I activity. Inhibition of mitochondrial complex I by metformin recapitulated the effects of canagliflozin on endocytosis and fluid transport, whereas modulation of downstream effectors AMPK and mTOR did not. Mice given a single dose of canagliflozin excreted twice as much urine over 24 h compared with empagliflozin-treated mice despite similar water intake. We conclude that canagliflozin selectively suppresses Na+-dependent fluid transport and albumin uptake in PT cells via direct inhibition of NHE3 and of mitochondrial function upstream of the AMPK/mTOR axis. These additional targets of canagliflozin contribute significantly to reduced PT Na+-dependent fluid transport in vivo.NEW & NOTEWORTHY Reduced NHE3-mediated Na+ transport has been suggested to underlie the cardiorenal protection provided by SGLT2 inhibitors. We found that canagliflozin, but not empagliflozin, reduced NHE3-dependent fluid transport and endocytic uptake in cultured proximal tubule cells. These effects were independent of SGLT2 activity and resulted from inhibition of mitochondrial complex I and NHE3. Studies in mice are consistent with greater effects of canagliflozin versus empagliflozin on fluid transport. Our data suggest that these selective effects of canagliflozin contribute to reduced Na+-dependent transport in proximal tubule cells.

Fe3+-induced coordination cross-linking gallic acid-carboxymethyl cellulose self-healing hydrogel.

Self-healing hydrogel is a promising soft material for applications in wound dressings, drug delivery, tissue engineering, biomimetic electronic skin, and wearable electronic devices. However, it is a challenge to fabricate the self-healing hydrogels without external stimuli. Inspired by mussel, the metal-catechol complexes were introduced into the hydrogel systems to prepare the mussel-inspired hydrogels by regulating the gelation kinetics of Fe3+ crosslinkers with gallic acid (GA) in this research. The amine-functionalized carboxymethyl cellulose (CMC) was grafted with GA and then chelated with Fe3+ to form a multi-response system. The crosslinking of carboxymethyl cellulose-ethylenediamine-gallic acid (CEG) hydrogel was controlled by adjusting the pH to affect the iron coordination chemistry, which could enhance the self-healing properties and mechanical strength of hydrogels. In addition, the CEG hydrogel exhibited great antibacterial and antioxidant properties. And the CEG hydrogel could strongly adhere to the skin tissue. The adhesion strength of CEG hydrogel on pigskin was 11.44 kPa, which is higher than that of commercial wound dressings (∼5 kPa). Moreover, the thixotropy of the CEG hydrogel was confirmed with rheological test. In summary, it has great potential in the application field of wound dressing.

OsALKBH9-mediated m6A demethylation regulates tapetal PCD and pollen exine accumulation in rice.

The N6-methyladenosine (m6A) mRNA modification is crucial for plant development and stress responses. In rice, the male sterility resulting from the deficiency of OsFIP37, a core component of m6A methyltransferase complex, emphasizes the significant role of m6A in male fertility. m6A is reversible and can be removed by m6A demethylases. However, whether mRNA m6A demethylase regulates male fertility in rice has remained unknown. Here, we identify the mRNA m6A demethylase OsALKBH9 and demonstrate its involvement in male fertility regulation. Knockout of OsALKBH9 causes male sterility, dependent on its m6A demethylation activity. Cytological analysis reveals defective tapetal programmed cell death (PCD) and excessive accumulation of microspores exine in Osalkbh9-1. Transcriptome analysis of anthers shows up-regulation of genes involved in tapetum development, sporopollenin synthesis, and transport pathways in Osalkbh9-1. Additionally, we demonstrate that OsALKBH9 demethylates the m6A modification in TDR and GAMYB transcripts, which affects the stability of these mRNAs and ultimately leads to excessive accumulation of pollen exine. Our findings highlight the precise control of mRNA m6A modification and reveal the pivotal roles played by OsALKBH9-mediated m6A demethylation in tapetal PCD and pollen exine accumulation in rice.

Granulation characteristics of anammox sludge in response to different signal-molecule-stimulants; mediated through programmed cell death.

During the anammox process, mitigation of biomass washout to increase sludge retention is an important parameter of process efficiency. Signal molecular stimulants (SMS) initiate the sludge granulations controlled by programmed cell death (PCD) of microorganisms. In this study, the aerobic granular sludge (AGS), cell fragments, extracellular polymeric substances (EPS), and AGS process effluent were tested as SMS to identify their effect on anammox granulation. The results showed that the addition of SMS increased the nitrogen removal efficiency to varying degrees, whereas the addition of AGS process supernatant, as SMS, increased the ammonia removal efficiency up to 96%. The addition of SMS was also found to increase EPS production and contributed to sludge granulation. In this process, the proportion of PCD increased and both Gaiella and Denitratisoma abundance increased from 3.54% to 5.59%, and from 1.8% to 3.42%, respectively. In conclusion, PCD was found important to increase anaerobic ammonia oxidation performance through the granulation mechanism.

Isotopic insights and integrated analysis for heavy metal levels, ecological risks, and source apportionment in river sediments of the Qinghai-Tibet Plateau.

The research was carried out to examine the pollution characteristics, ecological risk, and origins of seven heavy metals (Hg, As, Pb, Cu, Cd, Zn, and Ni) in 51 sediment samples gathered from 8 rivers located on the Qinghai-Tibet Plateau (QTP) in China. The contents of Hg and Cd were 5.0 and 1.1 times higher than their background values, respectively. The mean levels of other measured heavy metals were below those found naturally in the local soil. The enrichment factor showed that the study area exhibited significantly enriched Hg with 70.6% sampling sites. The Cd contents at 19.6% of sampling sites were moderately enriched. The other sampling sites were at a less enriched level. The sediments of all the rivers had a medium level of potential ecological risk. Hg was the major ecological risk factor in all sampling sites, followed by Cd. The findings from the positive matrix factorization (PMF) analysis shown agricultural activities, industrial activities, traffic emissions, and parent material were the major sources. The upper, middle, and low reaches of the Quanji river had different Hg isotope compositions, while sediments near the middle reaches were similar to the δ202Hg of the industrial source. At the upstream sampling sites, the Hg isotope content was very close to the background level. The results of this research can establish a strong scientific sound to improve the safety of the natural circumstances of rivers on the QTP.

Multi-omics provide insights into the regulation of DNA methylation in pear fruit metabolism.

BACKGROUND: Extensive research has been conducted on fruit development in crops, but the metabolic regulatory networks underlying perennial fruit trees remain poorly understood. To address this knowledge gap, we conduct a comprehensive analysis of the metabolome, proteome, transcriptome, DNA methylome, and small RNAome profiles of pear fruit flesh at 11 developing stages, spanning from fruitlet to ripening. Here, we systematically investigate the metabolic landscape and regulatory network involved. RESULTS: We generate an association database consisting of 439 metabolites and 14,399 genes to elucidate the gene regulatory network of pear flesh metabolism. Interestingly, we detect increased DNA methylation in the promoters of most genes within the database during pear flesh development. Application of a DNA methylation inhibitor to the developing fruit represses chlorophyll degradation in the pericarp and promotes xanthophyll, ß-carotene, and abscisic acid (ABA) accumulation in the flesh. We find the gradual increase in ABA production during pear flesh development is correlated with the expression of several carotenoid pathway genes and multiple transcription factors. Of these transcription factors, the zinc finger protein PbZFP1 is identified as a positive mediator of ABA biosynthesis in pear flesh. Most ABA pathway genes and transcription factors are modified by DNA methylation in the promoters, although some are induced by the DNA methylation inhibitor. These results suggest that DNA methylation inhibits ABA accumulation, which may delay fruit ripening. CONCLUSION: Our findings provide insights into epigenetic regulation of metabolic regulatory networks during pear flesh development, particularly with regard to DNA methylation.

Small-molecule agents for cancer immunotherapy.

Cancer immunotherapy, exemplified by the remarkable clinical benefits of the immune checkpoint blockade and chimeric antigen receptor T-cell therapy, is revolutionizing cancer therapy. They induce long-term tumor regression and overall survival benefit in many types of cancer. With the advances in our knowledge about the tumor immune microenvironment, remarkable progress has been made in the development of small-molecule drugs for immunotherapy. Small molecules targeting PRR-associated pathways, immune checkpoints, oncogenic signaling, metabolic pathways, cytokine/chemokine signaling, and immune-related kinases have been extensively investigated. Monotherapy of small-molecule immunotherapeutic drugs and their combinations with other antitumor modalities are under active clinical investigations to overcome immune tolerance and circumvent immune checkpoint inhibitor resistance. Here, we review the latest development of small-molecule agents for cancer immunotherapy by targeting defined pathways and highlighting their progress in recent clinical investigations.

A Two-Stage Noise-Tolerant Paradigm for Label Corrupted Person Re-Identification.

Supervised person re-identification (Re-ID) approaches are sensitive to label corrupted data, which is inevitable and generally ignored in the field of person Re-ID. In this paper, we propose a two-stage noise-tolerant paradigm (TSNT) for labeling corrupted person Re-ID. Specifically, at stage one, we present a self-refining strategy to separately train each network in TSNT by concentrating more on pure samples. These pure samples are progressively refurbished via mining the consistency between annotations and predictions. To enhance the tolerance of TSNT to noisy labels, at stage two, we employ a co-training strategy to collaboratively supervise the learning of the two networks. Concretely, a rectified cross-entropy loss is proposed to learn the mutual information from the peer network by assigning large weights to the refurbished reliable samples. Moreover, a noise-robust triplet loss is formulated for further improving the robustness of TSNT by increasing inter-class distances and reducing intra-class distances in the label-corrupted dataset, where a constraint condition for reliability discrimination is carefully designed to select reliable triplets. Extensive experiments demonstrate the superiority of TSNT, for instance, on the Market1501 dataset, our paradigm achieves 90.3% rank-1 accuracy (6.2% improvement over the state-of-the-art method) under noise ratio 20%.

The transcription factor PbbHLH164 is destabilized by PbRAD23C/D.1 and mediates ethylene biosynthesis during pear fruit ripening.

The phytohormone ethylene plays an important role in climacteric fruit ripening. However, the knowledge on molecular regulation of ethylene biosynthesis remains limited in pear fruit. Herein, a new basic helix-loop-helix transcription factor, PbbHLH164, was identified based on the transcriptome analysis of different developing and ripening fruits of two pear cultivars 'Sucui No. 1' and 'Cuiguan'. PbbHLH164 was more highly expressed in ripening fruit than in developing fruit and positively correlated with ethylene production in both cultivars. PbbHLH164 could directly bind to the promoter of 1-aminocyclopropane-1-carboxylate synthase, PbACS1b, to enhance the expression, leading to the increase of ethylene production and the acceleration of fruit ripening. Interestingly, PbbHLH164 physically interacted with an ubiquitin-like/ubiquitin-associated protein PbRAD23C/D.1, and the interaction of PbbHLH164 with PbRAD23C/D.1 attenuated the function of PbbHLH164 in enhancing the activity of the PbACS1b promoter. Notably, PbRAD23C/D.1 was involved in the degradation of PbbHLH164, and this degradation was inhibited by an ubiquitin proteasome inhibitor MG132. Different from PbbHLH164, PbRAD23C/D.1 was more highly expressed in developing fruit than in ripening fruit of both cultivars. These results suggest that the increase of ethylene production during pear fruit ripening results from the up-regulated expression of PbbHLH164 and the down-regulated expression of PbRAD23C/D.1. This information provided new insights into the molecular regulation of ethylene biosynthesis during fruit ripening.

Refined secondary Bjerknes force equation for double bubbles with pulsation, translation, and deformation.

The secondary Bjerknes force (SBF) is the time-averaged interaction between two bubbles driven in a sound field. We derived a refined formula for the interaction force, incorporating the radial vibration and translational and deformational motions of the bubble. The coupling of pulsation, translation, and deformation enhances the interaction between bubbles but also weakens their stability, making it easier for bubbles to merge or break during motion. The effects of the coupling mode on the magnitude and direction of SBFs coupled with pulsation, translation, and deformation were numerically analyzed and studied. Under certain sound-field conditions, the SBF increased with increasing pressure amplitude, initial radius, and initial velocity, while decreased as the distance increased. In addition, the SBF irregularly increased with increasing frequency.

3D bioprinting of GelMA with enhanced extrusion printability through coupling sacrificial carrageenan.

The potential of 3D bioprinting in tissue engineering and regenerative medicine is enormous, but its implementation is hindered by the reliance on high-strength materials, which restricts the use of low-viscosity, biocompatible materials. Therefore, a major challenge for incorporating 3D bioprinting into tissue engineering is to develop a novel bioprinting platform that can reversibly provide high biological activity materials with a structural support. This study presents a room temperature printing system based on GelMA combined with carrageenan to address this challenge. By leveraging the wide temperature stability range and lubricating properties of carrageenan the room temperature stability of GelMA could be enhanced, as well as creating a solid ink to improve the performance of solid GelMA. Additionally, by utilizing the solubility of carrageenan at 37 °C, it becomes possible to prepare a porous GelMA structure while mimicking the unique extracellular matrix properties of osteocytes through residual carrageenan content and amplifying BMSCs' osteogenesis potential to some extent. Overall, this study provides an innovative technical platform for incorporating a low-viscosity ink into 3D bioprinting and resolves the long-standing contradiction between material printing performance and biocompatibility in bioprinting technology.

Weakly Supervised Tracklet Association Learning With Video Labels for Person Re-Identification.

Supervised person re-identification (re-id) methods require expensive manual labeling costs. Although unsupervised re-id methods can reduce the requirement of the labeled datasets, the performance of these methods is lower than the supervised alternatives. Recently, some weakly supervised learning-based person re-id methods have been proposed, which is a balance between supervised and unsupervised learning. Nevertheless, most of these models require another auxiliary fully supervised datasets or ignore the interference of noisy tracklets. To address this problem, in this work, we formulate a weakly supervised tracklet association learning (WS-TAL) model only leveraging the video labels. Specifically, we first propose an intra-bag tracklet discrimination learning (ITDL) term. It can capture the associations between person identities and images by assigning pseudo labels to each person image in a bag. And then, the discriminative feature for each person is learned by utilizing the obtained associations after filtering the noisy tracklets. Based on that, a cross-bag tracklet association learning (CTAL) term is presented to explore the potential tracklet associations between bags by mining reliable positive tracklet pairs and hard negative pairs. Finally, these two complementary terms are jointly optimized to train our re-id model. Extensive experiments on the weakly labeled datasets demonstrate that WS-TAL achieves 88.1% and 90.3% rank-1 accuracy on the MARS and DukeMTMC-VideoReID datasets respectively. The performance of our model surpasses the state-of-the-art weakly supervised models by a large margin, even outperforms some fully supervised re-id models.

Insights into the effects of fixation methods on the sensory quality of straight-shaped green tea and dynamic changes of key taste metabolites by widely targeted metabolomic analysis.

Fresh leaves of Echa 1 were fixed by roller, steam/hot air and light-wave, and the effects of the three fixation methods on the chemical characteristics of straight-shaped green teas (GTs) were studied by widely targeted metabolomic analysis. 1001 non-volatile substances was identified, from which 97 differential metabolites were selected by the criteria of variable importance in projection (VIP) > 1, p < 0.05, and |log2(fold change)| > 1. Correlation analysis indicated that 14 taste-active metabolites were the major contributors to the taste differences between differently processed GTs. High-temperature fixation induces protein oxidation or degradation, γ-glutamyl peptide transpeptidation, degradation of flavonoid glycosides and epimerization of cis-catechins, resulting in the accumulation of amino acids, peptides, flavonoids and trans-catechins, which have flavor characteristics such as umami, sweetness, kokumi, bitterness and astringency, thereby affecting the overall taste of GTs. These findings provided a scientific basis for the directional processing technology of high-quality green tea.

Mineralocorticoid receptor-independent activation of ENaC in bile duct ligated mice.

Sodium and fluid retention in liver disease is classically thought to result from reduced effective circulating volume and stimulation of the renin-angiotensin-aldosterone system (RAAS). Aldosterone dives Na+ retention by activating the mineralocorticoid receptor and promoting the maturation and apical surface expression of the epithelial Na+ channel (ENaC), found in the aldosterone-sensitive distal nephron. However, evidence of fluid retention without RAAS activation suggests the involvement of additional mechanisms. Liver disease can greatly increase plasma and urinary bile acid concentrations and have been shown to activate ENaC in vitro. We hypothesize that elevated bile acids in liver disease activate ENaC and drive fluid retention independent of RAAS. We therefore increased circulating bile acids in mice through bile duct ligation (BDL) and measured effects on urine and body composition, while using spironolactone to antagonize the mineralocorticoid receptor. We found BDL lowered blood [K+] and hematocrit, and increased benzamil-sensitive natriuresis compared to sham, consistent with ENaC activation. BDL mice also gained significantly more body water. Blocking ENaC reversed fluid gains in BDL mice but had no effect in shams. In isolated collecting ducts from rabbits, taurocholic acid stimulated net Na+ absorption but had no effect on K+ secretion or flow-dependent ion fluxes. Our results provide experimental evidence for a novel aldosterone-independent mechanism for sodium and fluid retention in liver disease which may provide additional therapeutic options for liver disease patients.