Small Transjugular Intrahepatic Portosystemic Shunt Plus Variceal Embolization for Gastric Varices: A Multicenter Cohort Study.

BACKGROUND & AIMS: The effect of transjugular intrahepatic portosystemic shunt (TIPS) plus variceal embolization for treating gastric varices (GVs) remains controversial. This nationwide multicenter cohort study aimed to evaluate whether adding variceal embolization to a small diameter (8-mm) TIPS could reduce the rebleeding incidence in patients with different types of GVs. METHODS: This retrospective cohort study involved 629 patients who underwent 8-mm TIPS for gastric varices at 7 medical centers. The primary endpoint was all-cause rebleeding, and the secondary endpoints included overt hepatic encephalopathy (OHE) and all-cause mortality. RESULTS: A total of 629 patients were included. Among them, 429 (68.2%) had gastroesophageal varices type 1 (GOV1), 145 (23.1%) had gastroesophageal varices type 2 (GOV2), and 55 (8.7%) had isolated gastric varices type 1 (IGV1). In the entire cohort, adjunctive embolization reduced rebleeding (6.2% vs 13.6%; P = .005) and OHE (31.0% vs 39.4%; P = .02) compared with TIPS alone. However, no significant differences were found in mortality (12.0% vs 9.7%; P = .42). In patients with GOV2 and IGV1, TIPS plus variceal embolization reduced both rebleeding (GOV2: 7.8% vs 25.1%; P = .01; IGV1: 5.6% vs 30.8%; P = .03) and OHE (GOV2: 31.8% vs 51.5%; P = .008; IGV1: 11.6% vs 38.5%; P = .04). However, in patients with GOV1, adjunctive embolization did not reduce rebleeding (5.9% vs 8.7%; P = .37) or OHE (33.1% vs 35.3%; P = .60). CONCLUSIONS: Compared with TIPS alone, 8-mm TIPS plus variceal embolization reduced rebleeding and OHE in patients with GOV2 and IGV1. These findings suggest that patients with GOV2 and IGV1, rather than GOV1, could benefit from embolization with TIPS.

Composition and diversity of soil microbial communities change by introducing Phallus impudicus into a Gastrodia elata Bl.-based soil.

BACKGROUND: The Gastrodia elata Bl. is an orchid, and its growth demands the presence of Armillaria species. The strong competitiveness of Armillaria species has always been a concern of major threat to other soil organisms, thus disrupting the equilibrium of soil biodiversity. Introducing other species to where G. elata was cultivated, could possibly alleviate the problems associated with the disequilibrium of soil microenvironment; however, their impacts on the soil microbial communities and the underlying mechanisms remain unclear. To reveal the changes of microbial groups associated with soil chemical properties responding to different cultivation species, the chemical property measurements coupled with the next-generation pyrosequencing analyses were applied with soil samples collected from fallow land, cultivation of G. elata and Phallus impudicus, respectively. RESULTS: The cultivation of G. elata induced significant increases (p < 0.05) in soil pH and NO3-N content compared with fallow land, whereas subsequent cultivation of P. impudicus reversed these G. elata-induced increases and was also found to significantly increase (p < 0.05) the content of soil NH4+-N and AP. The alpha diversities of soil microbial communities were significantly increased (p < 0.01) by cultivation of G. elata and P. impudicus as indicated with Chao1 estimator and Shannon index. The structure and composition of soil microbial communities differed responding to different cultivation species. In particular, the relative abundances of Bacillus, norank_o_Gaiellales, Mortierella and unclassified_k_Fungi were significantly increased (p < 0.05), while the abundances of potentially beneficial genera such as Acidibacter, Acidothermus, Cryptococcus, and Penicillium etc., were significantly decreased (p < 0.05) by cultivation of G. elata. It's interesting to find that cultivation of P. impudicus increased the abundances of these genera that G. elata decreased before, which contributed to the difference of composition and structure. The results of CCA and heatmap indicated that the changes of soil microbial communities had strong correlations with soil nutrients. Specifically, among 28 genera presented, 50% and 42.9% demonstrated significant correlations with soil pH and NO3-N in response to cultivation of G. elata and P. impudicus. CONCLUSIONS: Our findings suggested that the cultivation of P. impudicus might have potential benefits as result of affecting soil microorganisms coupled with changes in soil nutrient profile.

USP29 activation mediated by FUBP1 promotes AURKB stability and oncogenic functions in gastric cancer.

BACKGROUND: Gastric cancer is a highly prevalent cancer type and the underlying molecular mechanisms are not fully understood. Ubiquitin-specific peptidase (USP) 29 has been suggested to regulate cell fate in several types of cancer, but its potential role in gastric carcinogenesis remains unclear. METHODS: The expression of USP29 in normal and gastric cancer tissues was analyzed by bioinformatics analysis, immunohistochemistry and immunoblot. Gene overexpression, CRISPR-Cas9 technology, RNAi, and Usp29 knockout mice were used to investigate the roles of USP29 in cell culture, xenograft, and benzo[a]pyrene (BaP)-induced gastric carcinogenesis models. We then delineated the underlying mechanisms using mass spectrometry, co-immunoprecipitation (Co-IP), immunoblot, ubiquitination assay, chromatin immunoprecipitation (ChIP), quantitative real-time PCR (qRT-PCR), and luciferase assays. RESULTS: In this study, we found that USP29 expression was significantly upregulated in gastric cancers and associated with poor patient survival. Ectopic expression of USP29 promoted, while depletion suppressed the tumor growth in vitro and in vivo mouse model. Mechanistically, transcription factor far upstream element binding protein 1 (FUBP1) directly activates USP29 gene transcription, which then interacts with and stabilizes aurora kinase B (AURKB) by suppressing K48-linked polyubiquitination, constituting a FUBP1-USP29-AURKB regulatory axis that medicates the oncogenic role of USP29. Importantly, systemic knockout of Usp29 in mice not only significantly decreased the BaP-induced carcinogenesis but also suppressed the Aurkb level in forestomach tissues. CONCLUSIONS: These findings uncovered a novel FUBP1-USP29-AURKB regulatory axis that may play important roles in gastric carcinogenesis and tumor progression, and suggested that USP29 may become a promising drug target for cancer therapy.

Chiral Pyclen-Based Heptadentate Chelates as Highly Stable MRI Contrast Agents.

In recent years, pyclen-based complexes have attracted a great deal of interest as magnetic resonance imaging (MRI) contrast agents (CAs) and luminescent materials, as well as radiopharmaceuticals. Remarkably, gadopiclenol, a Gd(III) bishydrated complex featuring a pyclen-based heptadentate ligand, received approval as a novel contrast agent for clinical MRI application in 2022. To maximize stability and efficiency, two novel chiral pyclen-based chelators and their complexes were developed in this study. Gd-X-PCTA-2 showed significant enhancements in both thermodynamic and kinetic stabilities compared to those of the achiral parent derivative Gd-PCTA. 1H NMRD profiles reveal that both chiral gadolinium complexes (Gd-X-PCTA-1 and Gd-X-PCTA-2) have a higher relaxivity than Gd-PCTA, while variable-temperature 17O NMR studies show that the two inner-sphere water molecules have distinct residence times τMa and τMb. Furthermore, in vivo imaging demonstrates that Gd-X-PCTA-2 enhances the signal in the heart and kidneys of the mice, and the chiral Gd complexes exhibit the ability to distinguish between tumors and normal tissues in a 4T1 mouse model more efficiently than that of the clinical agent gadobutrol. Biodistribution studies show that Gd-PCTA and Gd-X-PCTA-2 are primarily cleared by a renal pathway, with 24 h residues of Gd-X-PCTA-2 in the liver and kidney being lower than those of Gd-PCTA.

Titanium Nitride Nanorods Array-Decorated Graphite Felt as Highly Efficient Negative Electrode for Iron-Chromium Redox Flow Battery.

Iron-chromium redox flow batteries have attracted widespread attention because of their low cost. However, the performance of these batteries is still lower than that of vanadium redox flow batteries due to the poor electrochemical activity of Cr3+ /Cr2+ redox couples on graphite felt electrodes. Herein, binder-free TiN nanorods array-decorated 3D graphite felt composite electrode-is demonstrated. The dendrite-like TiN nanorods array increases the specific surface area of the electrode. The nitrogen and oxygen elements on the surface provide more adsorption sites and electrochemically active sites for Cr3+ /Cr2+ . The contact resistance of the composite electrode is effectively reduced and its homogeneity and stability are improved by avoiding the use of a binder and mixing process. A battery prepared using the TiN nanorods array-decorated 3D graphite felt electrode has enabled the maximum power density to be 427 mW·cm-2 , which is 74.0% higher than a battery assembled with TiN nanoparticles bonded to graphite felt. At a current density of 80 mA·cm-2 , the TiN nanorods battery exhibits the highest coulombic efficiency of 93.0%, voltage efficiency of 90.4%, and energy efficiency of 84.1%. Moreover, the battery efficiency and composite electrode structure remains stable during a redox flow battery cycle test.

Optical bistability modulation based on graphene sandwich structure with topological interface modes.

In this paper, we have investigated optical bistability modulation of transmitted beam that can be achieved by graphene sandwich structure with topological interface modes at terahertz frequency. Graphene with strong nonlinear optical effect was combined with sandwich photonic crystal to form a new sandwich structure with topological interface modes. The light-limiting properties of the topological interface modes, as well as its high unidirectionality and high transmission efficiency, all contribute positively to the reduction of the optical bistability threshold. In addition, the topological interface modes can effectively ensure the stability of the two steady state switching in the case of external interference. Moreover, optical bistability is closely related to the incident angle, the Fermi energy, the relaxation time, and the number of layers of graphene. Through parameter optimization, optical bistability with threshold of 105 V/m can be obtained, which has reached or is close to the range of the weak field.

Nonlinear optical bistability based on epsilon-near-zero mode in near-infrared band.

We propose a simple thin-layer structure based on epsilon-near-zero mode field enhancement to achieve optical bistability in the near-infrared band. The high transmittance provided by the thin-layer structure and the electric field energy limited in the ultra-thin epsilon-near-zero material means that the interaction between the input light and the epsilon-near-zero material can be greatly enhanced, creating favorable conditions for the realization of optical bistability in near-infrared band. The optical bistability hysteresis curve is closely related to the incident angle of light and the thickness of epsilon-near-zero material. This structure is relatively simple and easy to prepare, so we believe that this scheme will have a positive effect on the practicality of optical bistability devices in all-optical devices and networks.

Hepatic hydrothorax does not increase the risk of death after transjugular intrahepatic portosystemic shunt in cirrhosis patients.

OBJECTIVES: Hepatic hydrothorax (HH) is a predictor of poor survival in cirrhosis patients. However, whether HH increases the mortality risk of cirrhosis patients treated with transjugular intrahepatic portosystemic shunt (TIPS) is unknown. Our objective was to evaluate the influence of HH on the survival of cirrhosis patients after TIPS. METHODS: Cirrhosis patients with portal hypertension complications were selected from a prospective database of consecutive patients treated with TIPS in Xijing Hospital from January 2015 to June 2021. Cirrhosis patients with HH were treated as the experimental group. A control group of cirrhosis patients without HH was created using propensity score matching. Survival after TIPS and the related risk factors were analysed. RESULTS: There were 1292 cirrhosis patients with portal hypertension complications treated with TIPS, among whom 255 patients had HH. Compared with patients without HH, patients with HH had worse liver function (MELD, 12 vs. 10, p < 0.001), but no difference in survival after TIPS was observed. After propensity score matching, 243 patients with HH and 243 patients without HH were enrolled. There was no difference in cumulative survival between patients with and without HH. Cox regression analysis showed that HH was not associated with survival after TIPS, and main portal vein thrombosis (> 50%) was a prognostic factor of long-term survival after TIPS in cirrhosis patients (hazard ratio, 1.386; 95% CI, 1.030-1.865, p = 0.031). CONCLUSION: Hepatic hydrothorax does not increase the risk of death after TIPS in cirrhosis patients. KEY POINTS: • Hepatic hydrothorax is a decompensated event of cirrhosis and increases the risk of death. • Hepatic hydrothorax is associated with worse liver function. • Hepatic hydrothorax does not increase the mortality of cirrhosis treated with TIPS.

Enhanced antidepressant effects of BDNF-quercetin alginate nanogels for depression therapy.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) with neuronic development and function is a promising therapeutic agent for treating depressive disorder, according to the neurotrophin hypothesis. However, the delivery of BDNF into the brain is not easy as these large protein molecules cannot efficiently cross the blood-brain barrier (BBB) and easily suffer oxidative damage in vivo. Therefore, the quercetin-based alginate nanogels (quercetin nanogels) loaded with BDNF have been developed, which could efficiently bypass the BBB via the nose-to-brain pathway and protect BDNF from oxidative damage, providing an effective route for the therapy of depressive disorders by intranasal delivery. RESULTS: Quercetin nanogels exhibited uniform size distribution, excellent biocompatibility, and potent antioxidant and anti-inflammatory activities. Quercetin nanogels in the thermosensitive gel achieved sustained and controlled release of BDNF with non-Fick's diffusion, exhibited rapid brain distribution, and achieved nearly 50-fold enhanced bioavailability compared to oral quercetin. Quercetin nanogels as a therapeutic drug delivery carrier exerted antidepressant effects on reserpine-induced rats, effectively delivered BDNF to reverse despair behavior in stress-induced mice, and exhibited antidepressant effects on chronic mild unpredictable stimulation (CUMS) rats. These antidepressant effects of BDNF-Quercetin nanogels for CUMS rats are associated with the regulation of the glutamatergic system, PI3K-Akt, and BDNF-TrkB signaling pathway. CONCLUSIONS: In this study, we provide a promising strategy for brain delivery of BDNF for treating depressive disorders, effectively achieved through combining quercetin nanogels and intranasal administration.

Enolase, a cadmium resistance related protein from hyperaccumulator plant Phytolacca americana, increase the tolerance of Escherichia coli to cadmium stress.

Phytolacca americana is a Cd hyperaccumulator plant that accumulates significant amounts of Cd in leaves, making it a valuable phytoremediation plant species. Our previous research found enolase (ENO) may play an important part in P. americana to cope with Cd stress. As a multifunctional enzyme, ENO was involved not only in glycolysis but also in the response of plants to various environmental stresses. However, there are few studies on the function of PaENO (P. americana enolase) in coping with Cd stress. In this study, the PaENO gene was isolated from P. americana, and the expression level of PaENO gene significantly increased after Cd treatment. The enzymatic activity analysis showed PaENO had typical ENO activity, and the 42-position serine was essential to the enzymatic activity of PaENO. The Cd resistance assay indicated the expression of PaENO remarkably enhanced the resistance of E. coli to Cd, which was achieved by reducing the Cd content in E. coli. Moreover, both the expression of inactive PaENO and PaMBP-1 (alternative translation product of PaENO) can improve the tolerance of E. coli to Cd. The results indicated PaENO may be alternatively translated into the transcription factor PaMBP-1 to participate in the response of P. americana to Cd stress.

The expression of the Cd resistance related protein PaENO can significantly increase the tolerance of E. coli to Cd, which was achieved by reducing the content of Cd in E. coli cells, and was independent of the enzymatic activity of PaENO. Moreover, PaENO may be alternatively translated into the transcription factor PaMBP-1 to participate in the response of P. americana to Cd stress.

Phosphorus recovery from sewage sludge ash (SSA): An integrated technical, environmental and economic assessment of wet-chemical and thermochemical methods.

Incineration is a promising disposal method for sewage sludge (SS), enriching more than 90% of phosphorus (P) in the influent into the powdered product, sewage sludge ash (SSA), which is convenient for further P recovery. Due to insufficient bioavailable P and enriched heavy metals (HMs) in SSA, it is limited to be used directly as fertilizer. Hence, this paper provides an overview of P transformation in SS incineration, characterization of SSA components, and wet-chemical and thermochemical processes for P recovery with a comprehensive technical, economic, and environmental assessment. P extraction and purification is an important technical step to achieve P recovery from SSA, where the key to all technologies is how to achieve efficient separation of P and HMs at a low economic and environmental cost. It can be clear seen from the review that the economics of P recovery from SSA are often weak due to many factors. For example, the cost of wet-chemical methods is approximately 5∼6 €/kg P, while the cost of recovering P by thermochemical methods is about 2∼3 €/kg P, which is slightly higher than the current P fertilizer (1 €/kg P). So, for now, legislation is significant for promoting P recovery from SSA. In this regard, the relevant experience in Europe is worth learning from countries that have not yet carried out P recovery from SSA, and to develop appropriate policies and legislation according to their own national conditions.

[Cloning and functional verification of PhAEP gene, a key enzyme for biosynthesis of heterophyllin A in Pseudostellaria heterophylla].

This paper aimed to study the role of asparagine endopeptidase(AEP) gene in the biosynthesis mechanism of cyclic peptide compounds in Pseudostellaria heterophylla. The transcriptome database of P. heterophylla was systematically mined and screened, and an AEP gene, tentatively named PhAEP, was successfully cloned. The heterologous function verification by Nicotiana benthamiana showed that the expression of the gene played a role in the biosynthesis of heterophyllin A in P. heterophylla. Bioinformatics analysis showed that the cDNA of PhAEP was 1 488 bp in length, encoding 495 amino acids with a molecular weight of 54.72 kDa. The phylogenetic tree showed that the amino acid sequence encoded by PhAEP was highly similar to that of Butelase-1 in Clitoria ternatea, reaching 80%. The sequence homology and cyclase active site analysis revealed that the PhAEP enzyme may specifically hydrolyse the C-terminal Asn/Asp(Asx) site of the core peptide in the HA linear precursor peptide of P. heterophylla, thereby participating in the ring formation of the linear precursor peptide. The results of real-time quantitative polymerase chain reaction(RT-qPCR) showed that the expression level of PhAEP was the highest in fruits, followed by in roots, and the lowest in leaves. The heterophyllin A of P. heterophylla was detected in N. benthamiana that co-expressed PrePhHA and PhAEP genes instantaneously. In this study, the PhAEP gene, a key enzyme in the biosynthesis of heterophyllin A in P. heterophylla, has been successfully cloned, which lays a foundation for further analysis of the molecular mechanism of PhAEP enzyme in the biosynthesis of heterophyllin A in P. heterophylla and has important significance for the study of synthetic biology of cyclic peptide compounds in P. heterophylla.

Robust Heterostructures in Two-Dimensional Perovskites by Threshold-Dominating Anion Exchange.

Heterostructures play an irreplaceable role in high-performance optoelectronic devices. However, the preparation of robust perovskite heterostructures is challenging due to spontaneous interdiffusion of halogen anions. Herein, a vapor-phase anion exchange method universally suitable for the preparation of robust 2D Ruddlesden-Popper perovskite (RPP) heterostructures is developed. A variety of heterostructures are fabricated based on exfoliated RPP microplates (MPs). Depending on the specific organic cations, the heterostructures can be either sharp and uniform, or broad and gradient, suggesting a new anion diffusion behavior different from that in 3D perovskites. Further experimental studies reveal that the lateral transport of anions follows a threshold-dominating mechanism, while the vertical transport can be partially or completely suppressed by organic cations. Subsequently, quantitative investigation of anion diffusion in 2D perovskites is conducted. The lateral diffusion coefficient of halogen anions is calculated to be 6 to 7 orders of magnitude larger than the vertical coefficient, consistent with the observed highly anisotropic anion diffusion. In addition, it is shown that the anion exchange threshold can also enhance the thermodynamic stability of the heterostructures at elevated temperature. These results provide a general method to fabricate robust lateral RPP heterostructures, and offer important insights into anion behavior in low-dimensional perovskites.

Optical bistability modulation based on the photonic crystal Fabry-Perot cavity with graphene.

We investigate the low-threshold optical bistability of transmitted beams at the terahertz range based on the photonic crystal Fabry-Perot cavity with graphene. Graphene with strong nonlinear conductivity is placed in the middle of the Fabry-Perot cavity and the resonance of the cavity plays a positive role in promoting the low-threshold optical bistability. The optical bistability curve is closely related to the incident angle of light, the parameters of graphene, and the structural parameters of the Fabry-Perot cavity. Through parameter optimization, optical bistability with threshold of 105 V/m can be obtained, which has reached or is close to the range of the weak field.

Preliminary application of three-dimensional printing in congenital uterine anomalies based on three-dimensional transvaginal ultrasonographic data.

BACKGROUND: The three-dimensional (3D) printing technology has remarkable potential as an auxiliary tool for representing anatomical structures, facilitating diagnosis and therapy, and enhancing training and teaching in the medical field. As the most available diagnostic tool and it is routinely used as the first approach in diagnosis of the uterine anomalies, 3D transvaginal ultrasonography (3D-TVS) has been proposed as non-invasive "gold standard" approach for these malformations due to high diagnostic accuracy. Despite holding promise of manufacturing 3D printed models based on 3D-TVS data, relevant reports about 3D-TVS derived gynecological 3D printing haven't been reported to the best of our knowledge. We found an opportunity to explore the feasibility of building 3D printed models for the abnormal uterus based on the data acquired by 3D-TVS. METHODS: The women suspected with congenital uterine anomalies (CUAs) were enrolled in the study. The diagnose of CUAs were made by 3D-TVS scanning and further confirmed under the hysteroscopy examination. One volunteer with normal uterus was enrolled as control. All subjects underwent 3D-TVS scanning for 3D printing data collection. Acquired images were stored and extracted as DICOM files, then processed by professional software to portray and model the boundary of the uterine inner and outer walls separately. After the computer 3D models were constructed, the data were saved and output as STL files for further surface restoration and smoothing. The colors of endometrium and uterine body were specified, respectively, in the print preview mode. Then the uncured photosensitive resin was cleaned and polished to obtain a smooth and transparent solid model after printed models were cooled down. RESULTS: 3D printing models of normal uterus, incomplete septate uterus, complete septate uterus, uterus didelphys and unicornuate uterus were produced on ultrasonographic data of 3D-TVS. CONCLUSIONS: Our research and practice made the first try in modeling CUAs successfully based on ultrasonographic data entirely, verifying that it's a feasible way to build 3D printed models of high-quality through 3D-TVS scanning.

Denoising for 3D Point Cloud Based on Regularization of a Statistical Low-Dimensional Manifold.

A point cloud obtained by stereo matching algorithm or three-dimensional (3D) scanner generally contains much complex noise, which will affect the accuracy of subsequent surface reconstruction or visualization processing. To eliminate the complex noise, a new regularization algorithm for denoising was proposed. In view of the fact that 3D point clouds have low-dimensional structures, a statistical low-dimensional manifold (SLDM) model was established. By regularizing its dimensions, the denoising problem of the point cloud was expressed as an optimization problem based on the geometric constraints of the regularization term of the manifold. A low-dimensional smooth manifold model was constructed by discrete sampling, and solved by means of a statistical method and an alternating iterative method. The performance of the denoising algorithm was quantitatively evaluated from three aspects, i.e., the signal-to-noise ratio (SNR), mean square error (MSE) and structural similarity (SSIM). Analysis and comparison of performance showed that compared with the algebraic point-set surface (APSS), non-local denoising (NLD) and feature graph learning (FGL) algorithms, the mean SNR of the point cloud denoised using the proposed method increased by 1.22 DB, 1.81 DB and 1.20 DB, respectively, its mean MSE decreased by 0.096, 0.086 and 0.076, respectively, and its mean SSIM decreased by 0.023, 0.022 and 0.020, respectively, which shows that the proposed method is more effective in eliminating Gaussian noise and Laplace noise in common point clouds. The application cases showed that the proposed algorithm can retain the geometric feature information of point clouds while eliminating complex noise.

New Insights into TRP Ion Channels in Stem Cells.

Transient receptor potential (TRP) ion channels are cationic permeable proteins located on the plasma membrane. TRPs are cellular sensors for perceiving diverse physical and/or chemical stimuli; thus, serving various critical physiological functions, including chemo-sensation, hearing, homeostasis, mechano-sensation, pain, taste, thermoregulation, vision, and even carcinogenesis. Dysregulated TRPs are found to be linked to many human hereditary diseases. Recent studies indicate that TRP ion channels are not only involved in sensory functions but are also implicated in regulating the biological characteristics of stem cells. In the present review, we summarize the expressions and functions of TRP ion channels in stem cells, including cancer stem cells. It offers an overview of the current understanding of TRP ion channels in stem cells.

Activation of TRPV4 Induces Exocytosis and Ferroptosis in Human Melanoma Cells.

TRPV4 (transient receptor potential vanilloid 4), a calcium permeable TRP ion channel, is known to play a key role in endocytosis. However, whether it contributes to exocytosis remains unclear. Here, we report that activation of TRPV4 induced massive exocytosis in both melanoma A375 cell and heterologous expression systems. We show here that, upon application of TRPV4-specific agonists, prominent vesicle priming from endoplasmic reticulum (ER) was observed, followed by morphological changes of mitochondrial crista may lead to cell ferroptosis. We further identified interactions between TRPV4 and folding/vesicle trafficking proteins, which were triggered by calcium entry through activated TRPV4. This interplay, in turn, enhanced TRPV4-mediated activation of folding and vesicle trafficking proteins to promote exocytosis. Our study revealed a signaling mechanism underlying stimulus-triggered exocytosis in melanoma and highlighted the role of cellular sensor TRPV4 ion channel in mediating ferroptosis.

[Effect of Social Support on Multimorbidity and Related Outcomes of Middle-Aged and Older Adults in China].

Objective: To analyze the current status of social support for middle-aged and older adults with multimorbidity and to explore the correlation between different dimensions of social support and multimorbidity and the related outcomes on the basis of China Health and Retirement Longitudinal Study (CHARLS) 2015 survey data so as to reveal the complex social background of multimorbidity and the impact of social support on multimorbidity. Methods: A total of 9168 valid samples, with an average age of 59.60 years, were included in the study. Using the social support-related variables of the respondents, we conducted factor analysis and constructed regression models of common factors of social support and multimorbidity-related outcomes, intending to analyze the impact of common factors of social support on multimorbidity in the middle-aged and older adults. Results: The multimorbidity of middle-aged and older adults in China was related to multiple factors of social support, and the differences were statistically significant. Logistic regression showed that social support in the form of activity/recreational facilities and medical resources was a protective factor of multimorbidity, that family emotional support and economic support had a positive effect on life satisfaction of comorbid patients, and that social support in the form of education, social life and housing conditions was negatively correlated with catastrophic medical expenditure of the comorbid population ( P<0.05). Conclusion: Social support for middle-aged and older adults in China is unevenly distributed. Social support in the form of activity/recreational facilities and medical resources may reduce the risks of multimorbidity among middle-aged and older adults. Good family economic and emotional support can improve the life satisfaction of middle-aged and older adults with multimorbidity. Social support in the form of education, social life and housing conditions may reduce the risk of catastrophic medical expenditure in middle-aged and older adults with multimorbidity.

[Identification of miR160 family and their target genes in Rehmannia glutinosa in response to endophytic fungus GG22 infection].

This study aims to reveal the possible role of miR160 family in Rehmannia glutinosa in response to the infection of endophytic fungus Fusarium oxysporum GG22. Specifically, miR160 precursors and mature miR160 were retrieved from the small RNA database yielded by high-throughput sequencing. RNAfold was used to analyze the precursor structure, and DNAMAN and MEGA to analyze conservation and evolution of miR160 precursors and mature miR160. The target genes of miR160 were predicted and annotated, and the interaction was analyzed. Based on degradome sequencing, the target genes were further identified. The results showed that miR160 precursors had intact stem-loop structures. The precursor and mature sequences were conserved, particularly the 3 rd-16 th bases of the 5'-terminal. According to the phylogenetic tree, R. glutinosa had close evolutionary relationship with Arabidopsis thaliana, Oryza sativa, Salvia miltiorrhiza, and Sesamum indicum. A total of 22 target genes of miR160 were predicted and most of them were auxin response factor(ARF) genes. The target genes were involved in the Gene Ontology(GO) terms of biological processes, cellular components, and molecular functions. According to the degradome sequencing results, four target genes of miR160 were ARF(ARF18, ARF22) genes. R. glutinosa regulated its growth in response to the infection of endophytic fungus by changing the expression of miR160 and the target genes. qRT-PCR result of the differentially expressed rgl-miR160a and rgl-miR160a-3p was consistent with the sequencing result. This study clarifies the molecular mechanism of R. glutinosa in response to GG22 stress, laying a theoretical basis for the improvement and future research of R. glutinosa.