Orexin B protects dopaminergic neurons from 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity associated with reduced extracellular signal-regulated kinase phosphorylation.

BACKGROUND: The loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) is a major pathological hallmark of Parkinson's disease (PD). Orexin B (OXB) has been reported to promote the growth of DA neurons. However, the roles of OXB in the degeneration of DA neurons still remained not fully clear. METHODS: An in vivo PD model was constructed by administrating 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. Pole test was performed to investigate the motor function of mice and the number of DA neurons was detected by immunofluorescence (IF). A PD cell model was established by treating SH-SY5Y cells with 1-methyl-4-phenylpyridinium (MPP+). OXB was added to the culture medium 2 h after MPP + treatment. Microscopic analysis was carried out to investigate the function of OXB in the cell model of PD 24 h after MPP + challenge. RNA-Seq analysis of the PD cell model was performed to explore the possible mechanisms. Western blot was used to detect the phosphorylation levels of extracellular signal-regulated kinase (ERK). RESULTS: OXB significantly decreased the DA neurons death caused by MPTP, alleviated MPP+-induced neurotoxicity in SH-SY5Y cells, and robustly enhanced the weight and motor ability of PD mice. Besides, RNA-Seq analysis demonstrated that the mitogen-activated protein kinase (MAPK) pathway was involved in the pathology of PD. Furthermore, MPP + led to increased levels of phosphorylation of ERK (p-ERK), OXB treatment significantly decreased the levels of p-ERK in MPP+-treated SH-SY5Y cells. CONCLUSIONS: This study demonstrated that OXB exerts a neuroprotective role associated with reduced ERK phosphorylation in the PD model. This suggests that OXB may have therapeutic potential for treatment of PD.

Circ_BLNK is a Unique Molecular Marker in Non-small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) patients are characterized by distant metastasis and poor prognosis. Growing evidence has implied that circular RNAs (circRNAs) are involved in multiple tumor progression, including NSCLC. The objective of the present study was to functionally dissect the role and mechanism of circ_BLNK in NSCLC development and progression. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of circ_BLNK, miR-942-5p, and forkhead box protein O1 (FOXO1) in NSCLC tissues and cells. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, 5-ethynyl-2'-deoxyuridine (EdU) assay and colony formation assay detected cell proliferation; the protein expression levels were tested by western blot assay; cell apoptosis was measured by flow cytometry, and transwell assay detected cell migration and invasion. The molecular targeting relationship was determined by dual-luciferase reporter assay. The effect of circ_BLNK overexpression on tumor growth was detected by in vivo experiments and immunohistochemistry. Circ_BLNK was dramatically decreased in NSCLC, and overexpression of circ_BLNK inhibited proliferation, migration, and invasion of NSCLC cells and promoted cell apoptosis. Circ_BLNK level was negatively correlated with miR-942-5p expression and positively correlated with FOXO1 expression. Moreover, circ_BLNK acted as a sponge for miR-942-5p, which targeted FOXO1. Rescue assays presented that miR-942-5p reversed the anticancer action of circ_BLNK in NSCLC. Besides that, miR-942-5p inhibition suppressed the oncogenic behaviors, which were attenuated by FOXO1 knockdown. Animal experiments exhibited that circ_BLNK upregulation repressed tumor growth in vivo. Our study demonstrated a novel regulatory mechanism that circ_BLNK/miR-942-5p/FOXO1 axis adjusted non-small cell lung cancer development.

Horizontal transmission of a multidrug-resistant IncN plasmid isolated from urban wastewater.

Wastewater treatment plants (WWTPs) are considered reservoirs of antibiotic resistance genes (ARGs). Given that plasmid-mediated horizontal gene transfer plays a critical role in disseminating ARGs in the environment, it is important to inspect the transfer potential of transmissible plasmids to have a better understanding of whether these mobile ARGs can be hosted by opportunistic pathogens and should be included in One Health's considerations. In this study, we used a fluorescent-reporter-gene based exogenous isolation approach to capture extended-spectrum beta-lactamases encoding mobile determinants from sewer microbiome samples that enter an urban water system (UWS) in Denmark. After screening and sequencing, we isolated a ∼73 Kbp IncN plasmid (pDK_DARWIN) that harboured and expressed multiple ARGs. Using a dual fluorescent reporter gene system, we showed that this plasmid can transfer into resident urban water communities. We demonstrated the transfer of pDK_DARWIN to microbiome members of both the sewer (in the upstream UWS compartment) and wastewater treatment (in the downstream UWS compartment) microbiomes. Sequence similarity search across curated plasmid repositories revealed that pDK_DARWIN derives from an IncN backbone harboured by environmental and nosocomial Enterobacterial isolates. Furthermore, we searched for pDK_DARWIN sequence matches in UWS metagenomes from three countries, revealing that this plasmid can be detected in all of them, with a higher relative abundance in hospital sewers compared to residential sewers. Overall, this study demonstrates that this IncN plasmid is prevalent across Europe and an efficient vector capable of disseminating multiple ARGs in the urban water systems.

MoS2-Thin Film Transistor Based Flexible 2T1C Driving Circuits for Active-Matrix Displays.

Two-dimensional (2D) semiconductors offer great potential as high-performance materials for thin film transistors (TFTs) in displays. Their thin, stable, and flexible nature, along with excellent electrical properties, makes them suitable for flexible displays. However, previous demonstrations lacked clear superiority in pixel resolution and TFT performance. Here we present the flexible 2T1C pixel driving circuit for active-matrix displays based on high-quality large-scale monolayer MoS2. A gate-first fabrication process was developed for flexible MoS2-TFTs, showing a remarkable carrier mobility (average at 52.8 cm2 V-1 s-1), high on/off ratio (average at 1.5 × 108), and negligible hysteresis. The driving current can be modulated by pulsed input voltages and demonstrates a stable and prompt response to both frequency and amplitude. We also demonstrated a 10 × 10 active-matrix with high resolution of 508 pixels per inch, exhibiting 100% yield and high uniformity. The driving circuit works well under bending up to ∼0.91% strain, highlighting its normal functions in flexible displays.

Scaling of MoS2 Transistors and Inverters to Sub-10 nm Channel Length with High Performance.

Two-dimensional (2D) semiconductors such as monolayer molybdenum disulfide (MoS2) are promising building blocks for ultrascaled field effect transistors (FETs), benefiting from their atomic thickness, dangling-bond-free flat surface, and excellent gate controllability. However, despite great prospects, the fabrication of 2D ultrashort channel FETs with high performance and uniformity remains a challenge. Here, we report a self-encapsulated heterostructure undercut technique for the fabrication of sub-10 nm channel length MoS2 FETs. The fabricated 9 nm channel MoS2 FETs exhibit superior performances compared with sub-15 nm channel length including the competitive on-state current density of 734/433 µA/µm at VDS = 2/1 V, record-low DIBL of ∼50 mV/V, and superior on/off ratio of 3 × 107 and low subthreshold swing of ∼100 mV/dec. Furthermore, the ultrashort channel MoS2 FETs fabricated by this new technique show excellent homogeneity. Thanks to this, we scale the monolayer inverter down to sub-10 nm channel length.

The Efficacy of Defocus Incorporated Multiple Segments Lenses in Slowing Myopia Progression: Results from Diverse Clinical Circumstances.

PURPOSE: Defocus incorporated multiple segments (DIMS) spectacle lenses were reported to slow myopia progression significantly in a randomized controlled trial (RCT). The study evaluated their effectiveness in clinical settings. DESIGN: Retrospective study. PARTICIPANTS: Patient records involving use of DIMS and single-vision (SV) spectacle lenses were collected from subsidiary hospitals of Aier Eye Hospital Group. METHODS: The spherical equivalent (SE), determined by subjective refraction, was adopted to assess the myopia progression. The strategy of propensity score matching (PSM) was applied to match the confounding baseline characteristics between the 2 groups. The effectiveness was calculated based on the difference of myopia progression of these 2 approaches. MAIN OUTCOME MEASURES: Change in SE. RESULTS: Three thousand six hundred thirty-nine patients with DIMS and 6838 patients with SV spectacles were included. The age of the patients was 6 to 16 years (mean ± standard deviation: 11.02 ± 2.53 years). The baseline SE was between 0.00 and -10.00 diopters (D) (mean ± standard deviation: -2.78 ± 1.74 D). After the PSM, data on 2240 pairs with 1-year follow-up and on 735 pairs with 2-year follow-up were obtained. Significantly slower progression was seen in the DIMS group at both the 1-year (DIMS, -0.50 ± 0.43 D; SV, -0.77 ± 0.58 D; P < 0.001) and 2-year (DIMS, -0.88 ± 0.62 D; SV, -1.23 ± 0.76 D; P < 0.001) subdataset. In the 1-year subdataset, 40% and 19% showed myopia progression of no more than 0.25 D for the DIMS and SV groups, respectively (chi-square, 223.43; P < 0.001), whereas 9% and 22% showed myopia progression of more than 1.00 D for the DIMS and SV groups, respectively (chi-square, 163.38; P < 0.001). In the 2-year subdataset, 33% and 20% showed myopia progression of no more than 0.50 D for the DIMS and SV groups, respectively (chi-square, 31.15; P < 0.001), whereas 12% and 29% showed myopia progression of more than 1.50 D for the DIMS and SV groups (chi-square, 65.60; P < 0.001). CONCLUSIONS: Although the magnitude was lower than that reported in the previous RCT, this large-scale study with diversity of the data sources confirmed the effectiveness of DIMS spectacles to slow myopia progression in clinical practice. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Giant Correlated Gap and Possible Room-Temperature Correlated States in Twisted Bilayer MoS_{2}.

Moiré superlattices have emerged as an exciting condensed-matter quantum simulator for exploring the exotic physics of strong electronic correlations. Notable progress has been witnessed, but such correlated states are achievable usually at low temperatures. Here, we report evidence of possible room-temperature correlated electronic states and layer-hybridized SU(4) model simulator in AB-stacked MoS_{2} homobilayer moiré superlattices. Correlated insulating states at moiré band filling factors v=1, 2, 3 are unambiguously established in twisted bilayer MoS_{2}. Remarkably, the correlated electronic state at v=1 shows a giant correlated gap of ∼126 meV and may persist up to a record-high critical temperature over 285 K. The realization of a possible room-temperature correlated state with a large correlated gap in twisted bilayer MoS_{2} can be understood as the cooperation effects of the stacking-specific atomic reconstruction and the resonantly enhanced interlayer hybridization, which largely amplify the moiré superlattice effects on electronic correlations. Furthermore, extreme large nonlinear Hall responses up to room temperature are uncovered near correlated electronic states, demonstrating the quantum geometry of moiré flat conduction band.

Circ_0082182 upregulates the NFIB level via sponging miR-326 to promote oxaliplatin resistance and malignant progression of colorectal cancer cells.

Circular RNAs (circRNAs) are key regulators in tumor metastasis and drug resistance. This study was designed to investigate circ_0082182 function and mechanism in oxaliplatin (OXA) resistance and cancer progression of colorectal cancer (CRC). The circ_0082182, microRNA-326 (miR-326), and nuclear factor I B (NFIB) levels were quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell sensitization was analyzed by Cell Counting Kit-8 assay. The proliferation ability was determined via EdU assay, and apoptosis was measured by flow cytometry. Transwell assay and wound healing assay were performed to assess cell invasion and migration. The protein level was examined through Western blot. The binding interaction was conducted via dual-luciferase reporter assay. Xenograft tumor assay was used to explore the circ_0082182 function in vivo. The circ_0082182 level was upregulated in OXA-resistant CRC samples and cells. Downregulation of circ_0082182 suppressed OXA resistance, proliferation, invasion, and migration but promoted apoptosis of OXA-resistant CRC cells. Circ_0082182 acted as a sponge for miR-326. The regulatory role of circ_0082182 was ascribed to the miR-326 sponging function. MiR-326 directly targeted NFIB to impede OXA resistance and cancer progression in CRC cells. NFIB level was regulated by circ_0082182 via sponging miR-326. Circ_0082182 promoted tumor growth in OXA-resistant xenograft tumor model through mediating the miR-326/NFIB axis. These data suggested that circ_0082182 elevated the NFIB expression to regulate OXA resistance and CRC progression by absorbing miR-326.

TRIM64 promotes ox-LDL-induced foam cell formation, pyroptosis, and inflammation in THP-1-derived macrophages by activating a feedback loop with NF-κB via IκBα ubiquitination.

Atherosclerosis is a chronic inflammatory disease and the main pathology behind most cardiovascular diseases and the overactivation of macrophages initiates the development of atherosclerosis. However, the specific functions of oxidized low-density lipoprotein (ox-LDL) in macrophages remain elusive. Macrophages derived from monocyte (THP-1) were treated with ox-LDL and were used to generate atherosclerosis in an in vitro model. NLRP3 inflammasome markers were examined using quantitative RT-PCR and Western blotting. Cytokines were measured using ELISA. Chromatin immunoprecipitation (ChIP) was utilized to detect nuclear factor kappa B (NF-κB) and TRIM64 interactions. A fat-rich diet was applied to ApoE-/- mice for in vivo studies. ox-LDL promoted TRIM64 expression in a time-dependent manner. According to loss- and gain-of-function analyses, TRIM64 enhanced the activation of NLRP3 inflammasomes and the expression of downstream molecules. TRIM64 directly interacted with IκBα and promoted IκBα ubiquitination at K67 to activate NF-κB signaling. We detected direct binding between NF-κB and the TRIM64 promoter, as well as enhanced TRIM64 expression. Our study revealed an interaction between TRIM64 and NF-κB in the development of atherosclerosis. TRIM64 and NF-κB formed a positive feedback to activate NF-κB pathway. ox-LDL induces foam cell formation and TRIM64 expression TRIM64 regulates ox-LDL-induced foam cell formation, pyroptosis and inflammation via the NF-κB signaling TRIM64 activates NF-κB signaling by ubiquitination of IκBα NF-κB inhibition attenuates atherosclerosis in HFD-induced ApoE (-/-) mice.

The human tRNA taurine modification enzyme GTPBP3 is an active GTPase linked to mitochondrial diseases.

GTPBP3 and MTO1 cooperatively catalyze 5-taurinomethyluridine (τm5U) biosynthesis at the 34th wobble position of mitochondrial tRNAs. Mutations in tRNAs, GTPBP3 or MTO1, causing τm5U hypomodification, lead to various diseases. However, efficient in vitro reconstitution and mechanistic study of τm5U modification have been challenging, in part due to the lack of pure and active enzymes. A previous study reported that purified human GTPBP3 (hGTPBP3) is inactive in GTP hydrolysis. Here, we identified the mature form of hGTPBP3 and showed that hGTPBP3 is an active GTPase in vitro that is critical for tRNA modification in vivo. Unexpectedly, the isolated G domain and a mutant with the N-terminal domain truncated catalyzed GTP hydrolysis to only a limited extent, exhibiting high Km values compared with that of the mature enzyme. We further described several important pathogenic mutations of hGTPBP3, associated with alterations in hGTPBP3 localization, structure and/or function in vitro and in vivo. Moreover, we discovered a novel cytoplasm-localized isoform of hGTPBP3, indicating an unknown potential noncanonical function of hGTPBP3. Together, our findings established, for the first time, the GTP hydrolysis mechanism of hGTPBP3 and laid a solid foundation for clarifying the τm5U modification mechanism and etiology of τm5U deficiency-related diseases.

MKRN3-mediated ubiquitination of Poly(A)-binding proteins modulates the stability and translation of GNRH1 mRNA in mammalian puberty.

The family of Poly(A)-binding proteins (PABPs) regulates the stability and translation of messenger RNAs (mRNAs). Here we reported that the three members of PABPs, including PABPC1, PABPC3 and PABPC4, were identified as novel substrates for MKRN3, whose deletion or loss-of-function mutations were genetically associated with human central precocious puberty (CPP). MKRN3-mediated ubiquitination was found to attenuate the binding of PABPs to the poly(A) tails of mRNA, which led to shortened poly(A) tail-length of GNRH1 mRNA and compromised the formation of translation initiation complex (TIC). Recently, we have shown that MKRN3 epigenetically regulates the transcription of GNRH1 through conjugating poly-Ub chains onto methyl-DNA bind protein 3 (MBD3). Therefore, MKRN3-mediated ubiquitin signalling could control both transcriptional and post-transcriptional switches of mammalian puberty initiation. While identifying MKRN3 as a novel tissue-specific translational regulator, our work also provided new mechanistic insights into the etiology of MKRN3 dysfunction-associated human CPP.

Hederasaponin C inhibits LPS-induced acute kidney injury in mice by targeting TLR4 and regulating the PIP2/NF-κB/NLRP3 signaling pathway.

Acute kidney injury (AKI) is a common clinical condition associated with increased incidence and mortality rates. Hederasaponin C (HSC) is one of the main active components of Pulsatilla chinensis (Bunge) Regel. HSC possesses various pharmacological activities, including anti-inflammatory activity. However, the protective effect of HSC against lipopolysaccharide (LPS)-induced AKI in mice remains unclear. Therefore, we investigated the protective effect of HSC against LPS-induced renal inflammation and the underlying molecular mechanisms. Herein, using MTT and LDH assays to assess both cell viability and LDH activity; using dual staining techniques to identify different cell death patterns; conducting immunoblotting, QRT-PCR, and immunofluorescence analyses to evaluate levels of protein and mRNA expression; employing immunoblotting, molecular docking, SPR experiments, and CETSA to investigate the interaction between HSC and TLR4; and studying the anti-inflammatory effects of HSC in the LPS-induced AKI. The results indicate that HSC inhibits the expression of TLR4 and the activation of NF-κB and PIP2 signaling pathways, while simultaneously suppressing the activation of the NLRP3 inflammasome. In animal models, HSC ameliorated LPS-induced AKI and diminished inflammatory response and the level of renal injury markers. These findings suggest that HSC has potential as a therapeutic agent to mitigate sepsis-related AKI.

Dihydrotanshinone Triggers Porimin-Dependent Oncosis by ROS-Mediated Mitochondrial Dysfunction in Non-Small-Cell Lung Cancer.

Lung cancer is one of the leading causes of cancer death. Non-small-cell lung cancer (NSCLC) accounts for the majority of lung cancer diagnoses. Dihydrotanshinone (DHT) is a compound extract from Salvia miltiorrhiza, which has favorable anti-inflammatory and anti-cancer activities. However, the role of DHT in NSCLC has not been fully studied. The anti-cancer drugs used for treating lung cancer often lead to apoptosis; however, the drug resistance of apoptosis restricts the effect of these drugs. Oncosis is a passive form of cell death that is different from apoptosis. It is characterized by cell swelling, and Porimin is a specific marker for oncosis. In this study, the role of DHT in mediating oncosis in A549 cells was investigated. In vitro, the MTS assay was used to detect cell activity after DHT treatment. Microscopy and electron microscopy were used to observe cell morphology changes. Western blotting was used to detect protein expression. Flow cytometry was used to detect intracellular reactive oxygen species (ROS) level, calcium ion (Ca2+) level, and cell mortality. The intracellular Lactic dehydrogenase (LDH) level was detected by an LDH detection kit after DHT treatment. The ATP level was detected using an ATP detection kit. In vivo, Lewis lung cancer (LLC) xenograft mice were used to evaluate the anti-tumor effect of DHT. Hematoxylin and eosin (HE) staining was used to detect the pathology of lung cancer tumors. The detection of Porimin in the tumor tissues of the mice after DHT administration was assessed by immunohistochemistry (IHC). The results of this study showed that DHT treatment changed the cell morphology; destroyed the mitochondrial structure; increased the expression of Porimin; increased the levels of LDH, ROS, and Ca2+; decreased the mitochondrial membrane potential and ATP level; and played an anti-tumor role in vitro by mediating oncosis in A549 cells. The in vivo studies showed that DHT could effectively inhibit tumor growth. The results of protein detection and IHC detection in the tumor tissues showed that the expression of Porimin was increased and that oncosis occurred in the tumor tissues of mice. DHT triggered Porimin-dependent oncosis by ROS-mediated mitochondrial dysfunction in NSCLC. The in vivo studies showed that DHT could inhibit tumor growth in LLC xenograft mice by triggering oncosis. This study indicates the potential for DHT to treat NSCLC.

Deactivation and Regeneration of Nitrogen Doped Carbon Catalyst for Acetylene Hydrochlorination.

The poor stability of carbon materials doped with nitrogen limited their development in acetylene hydrochlorination. Therefore, investigating the deactivation reasons of carbon catalysts and researching regeneration methods became the research focus. Herein, carbon-nitrogen materials were synthesized by one-step pyrolysis, which using biomass materials with high nitrogen content, the synthesized material was used in an acetylene hydrochlorination reaction. The acetylene conversion rate of D-GH-800 catalyst was up to 99%, but the catalytic activity decreased by 30% after 60 h reaction. Thermogravimetric analysis results showed that the coke content was 5.87%, resulting in catalyst deactivation. Temperature-programmed desorption verified that the deactivation was due to the strong adsorption and difficult desorption of acetylene by the D-GH-800 catalyst, resulting in the accumulation of acetylene on the catalyst surface to form carbon polymers and leading to the pore blockage phenomenon. Furthermore, based on the catalyst deactivation by carbon accumulation, we proposed a new idea of regeneration by ZnCl2 activation to eliminate carbon deposition in the pores of the deactivated catalyst. As a result, the activity of D-GH-800 was recovered, and lifetime was also extended. Our strategy illustrated the mechanism of carbon deposition, and the recoverability of the catalyst has promising applications.

Synthesis and Performance Analysis of Green Water and Oil-Repellent Finishing Agent with Di-Short Fluorocarbon Chain.

A novel fluorine-containing water-repellent agent (OFAE-SA-BA) was designed and synthesized by emulsion copolymerization, which was used to replace the commercial long fluorocarbon chain water-repellent agent. To improve water repellency, the intermediate and monomer containing two short fluoroalkyl chains were successfully synthesized and characterized by 1H NMR, 13C NMR and FT-IR, respectively. After being treated by the water-repellent agent, the surface chemical composition, molecular weight, thermal stability, surface morphology, wetting behavior, and durability of the modified cotton fabrics were characterized using X-ray photoelectron spectrophotometry (XPS), gel permeation chromatography (GPC), thermal degradation (TG), scanning electron microscopy (SEM), and video-based contact angle goniometry, respectively. The cotton fabric demonstrated water contact angle of 154.1°, both the water and oil repellency rating were grade 4. The durability of water repellency of the treated fabrics only decreased slightly after 30 times, which represented very good washing durability. The finishing agent did not affect the whiteness of the fabric.

An easily modifiable conjugative plasmid for studying horizontal gene transfer.

Horizontal gene transfer is an important mechanism in bacterial evolution and can occur at striking frequencies when mediated by mobile genetic elements. Conjugative plasmids are mobile genetic elements that are main drivers of horizontal transfer and a major facilitator in the spread of antibiotic resistance genes. However, conjugative plasmid models that readily can be genetically modified with the aim to study horizontal transfer are not currently available. The aim of this study was to develop a conjugative plasmid model where the insertion of gene cassettes such as reporter genes (e.g., fluorescent proteins) or antibiotic resistance genes would be efficient and convenient. Here, we introduced a single attTn7 site into the conjugative broad-host-range IncP-1 plasmid pKJK5 in a non-disruptive manner. Furthermore, a version with lower transfer rate and a non-conjugative version of pKJK5-attTn7 were also constructed. The advantage of having the attTn7 sites is that genes of interest can be introduced in a single step with very high success rate using the Tn7 transposition system. In addition, larger genetic fragments can be inserted. To illustrate the efficacy of the constructed pKJK5 plasmids, they were complemented with sfGFP (a gene encoding superfolder green fluorescent protein) in addition to seven different ß-lactamase genes representing the four known classes of ß-lactamases.

Platelet-to-lymphocyte ratio and the first occurrence of peritonitis in peritoneal dialysis patients.

BACKGROUND: Platelet-to-lymphocyte ratio (PLR) has been used as a potential biomarker of inflammation-related diseases, but its role in the peritoneal dialysis-related peritonitis (PDRP) is still uncertain. This study was aimed to investigate the association between PLR and the new-onset PDRP in peritoneal dialysis (PD) patients. METHODS: In this multicenter retrospective study, 1378 PD Chinese PD patients were recruited from four centers, who were divided into the high PLR group (HPG) and the low PLR group (LPG) according to the cutoff value of PLR. The correlation between PLR and the new-onset PDRP was assessed using the Cox regression model analysis. RESULTS: During follow-up, 121 new-onset PDRP events were recorded. Kaplan-Meier survival curve showed a higher risk of new-onset PDRP in the HPG (log-rank test, P < 0.001). After adjusting for confounding factors, the Cox regression model showed the risk of new-onset PDRP was higher in the HPG than that in the LPG (HR 1.689, 95%CI 1.096-2.602, P = 0.017). Competitive risk model analysis showed that significant differences still existed between the two PLR groups in the presence of other competitive events (P < 0.001). CONCLUSION: PLR is independently associated with the new-onset PDRP in PD patients.

Cotton transcriptome analysis reveals novel biological pathways that eliminate reactive oxygen species (ROS) under sodium bicarbonate (NaHCO3) alkaline stress.

Alkaline stress is one of the abiotic stresses limiting cotton production. Though RNA-Seq analyses, have been conducted to investigate genome-wide gene expression in response to alkaline stress in plants, the response of sodium bicarbonate (NaHCO3) stress-related genes in cotton has not been reported. To explore the mechanisms of cotton response to this alkaline stress, we used next-generation sequencing (NGS) technology to study transcriptional changes of cotton under NaHCO3 alkaline stress. A total of 18,230 and 11,177 differentially expressed genes (DEGs) were identified in cotton roots and leaves, respectively. Gene ontology (GO) analysis indicated the enrichment of DEGs involved in various stimuli or stress responses. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that DEGs associated with plant hormone signal transduction, amino acid biosynthesis, and biosynthesis of secondary metabolites were regulated in response to the NaHCO3 stress. We further analyzed genes enriched in secondary metabolic pathways and found that secondary metabolites were regulated to eliminate the reactive oxygen species (ROS) and improve the cotton tolerance to the NaHCO3 stress. In this study, we learned that the toxic effect of NaHCO3 was more profound than that of NaOH at the same pH. Thus, Na+, HCO3- and pH had a great impact on the growth of cotton plant. The novel biological pathways and candidate genes for the cotton tolerance to NaHCO3 stress identified from the study would be useful in the genetic improvement of the alkaline tolerance in cotton.

The relationship between platelet distribution width and new-onset cardiovascular disease events in patients with peritoneal dialysis.

OBJECTIVES: The global mortality rate from chronic kidney disease (CKD) has increased over the past two decades. Typically, peritoneal dialysis (PD) remains a useful alternative treatment for end-stage renal disease. Cardiovascular disease (CVD) is the main complication in PD patients. In terms of prognosis, it is reported that platelet distribution width (PDW) can predict adverse CVD events. However, the relationship between PDW and new-onset CVD in PD patients is not clear. This study aimed to explore the relationship between PDW and new-onset CVD in PD patients. METHODS: This was a retrospective cohort study, from 4 July 2005 to 31 December 2019, and a total of 1557 patients were recruited. PDW was respectively categorized into two groups: PDW ≤13.2 fL and PDW >13.2 fL. The primary outcome was a new-onset CVD event. Cox proportional hazards models were performed to assess the hazard ratio (HR). Receiver-operating characteristic (ROC) curves were applied to evaluate the predictive accuracy of the PDW on CVD events. RESULTS: During follow-up, 114 new-onset CVD events were recorded. Cox proportional hazards models showed a higher risk of CVD events in patients with high PDW (HR = 1.862 95%CI 1.205-2.877, p = 0.005). Kaplan-Meier cumulative incidence curves showed the risk of the first occurrence of CVD events was greater in the high PDW group (p = 0.006). CONCLUSIONS: High PDW is associated with new-onset cardiovascular disease events in PD patients.

Genome-wide identification and function analysis of HMAD gene family in cotton (Gossypium spp.).

BACKGROUND: The abiotic stress such as soil salinization and heavy metal toxicity has posed a major threat to sustainable crop production worldwide. Previous studies revealed that halophytes were supposed to tolerate other stress including heavy metal toxicity. Though HMAD (heavy-metal-associated domain) was reported to play various important functions in Arabidopsis, little is known in Gossypium. RESULTS: A total of 169 G. hirsutum genes were identified belonging to the HMAD gene family with the number of amino acids ranged from 56 to 1011. Additionally, 84, 76 and 159 HMAD genes were identified in each G. arboreum, G. raimondii and G. barbadense, respectively. The phylogenetic tree analysis showed that the HMAD gene family were divided into five classes, and 87 orthologs of HMAD genes were identified in four Gossypium species, such as genes Gh_D08G1950 and Gh_A08G2387 of G. hirsutum are orthologs of the Gorai.004G210800.1 and Cotton_A_25987 gene in G. raimondii and G. arboreum, respectively. In addition, 15 genes were lost during evolution. Furthermore, conserved sequence analysis found the conserved catalytic center containing an anion binding (CXXC) box. The HMAD gene family showed a differential expression levels among different tissues and developmental stages in G. hirsutum with the different cis-elements for abiotic stress. CONCLUSIONS: Current study provided important information about HMAD family genes under salt-stress in Gossypium genome, which would be useful to understand its putative functions in different species of cotton.