Rapid Detection of Bacterial Pathogens Causing Lower Respiratory Tract Infections via Microfluidic-Chip-Based Loop-Mediated Isothermal Amplification.

Respiratory tract infections (RTIs) are among the most common problems in clinical settings. Rapid and accurate identification of bacterial pathogens will provide practical guidelines for managing and treating RTIs. This study describes a method for rapidly detecting bacterial pathogens that cause respiratory tract infections via multi-channel loop-mediated isothermal amplification (LAMP). LAMP is a sensitive and specific diagnostic tool that rapidly detects bacterial nucleic acids with high accuracy and reliability. The proposed method offers a significant advantage over traditional bacterial culturing methods, which are time-consuming and often require greater sensitivity for detecting low levels of bacterial nucleic acids. This article presents representative results of K. pneumoniae infection and its multiple co-infections using LAMP to detect samples (sputum, bronchial lavage fluid, and alveolar lavage fluid) from the lower respiratory tract. In summary, the multi-channel LAMP method provides a rapid and efficient means of identifying single and multiple bacterial pathogens in clinical samples, which can help prevent the spread of bacterial pathogens and aid in the appropriate treatment of RTIs.

Long non­coding RNA DANCR aggravates breast cancer through the miR­34c/E2F1 feedback loop.

Emerging scientific evidence has suggested that the long non­coding (lnc)RNA differentiation antagonizing non­protein coding RNA (DANCR) serves a significant role in human tumorigenesis and cancer progression; however, the precise mechanism of its function in breast cancer remains to be fully understood. Therefore, the objective of the present study was to manipulate DANCR expression in MCF7 and MDA­MB­231 cells using lentiviral vectors to knock down or overexpress DANCR. This manipulation, alongside the analysis of bioinformatics data, was performed to investigate the potential mechanism underlying the role of DANCR in cancer. The mRNA and/or protein expression levels of DANCR, miR­34c­5p and E2F transcription factor 1 (E2F1) were assessed using reverse transcription­quantitative PCR and western blotting, respectively. The interactions between these molecules were validated using chromatin immunoprecipitation and dual­luciferase reporter assays. Additionally, fluorescence in situ hybridization was used to confirm the subcellular localization of DANCR. Cell proliferation, migration and invasion were determined using 5­ethynyl­2'­deoxyuridine, wound healing and Transwell assays, respectively. The results of the present study demonstrated that DANCR had a regulatory role as a competing endogenous RNA and upregulated the expression of E2F1 by sequestering miR­34c­5p in breast cancer cells. Furthermore, E2F1 promoted DANCR transcription by binding to its promoter in breast cancer cells. Notably, the DANCR/miR­34c­5p/E2F1 feedback loop enhanced cell proliferation, migration and invasion in breast cancer cells. Thus, these findings suggested that targeting DANCR may potentially provide a promising future therapeutic strategy for breast cancer treatment.

Ultrasensitive Biomimetic Skin with Multimodal and Photoelectric Dual-Signal Sensing.

Mimicking biological skin enabling direct, intelligent interaction between users and devices, multimodal sensing with optical/electrical (OE) output signals is urgently required. Owing to this, this work aims to logically design a stretchable OE biomimetic skin (OE skin), which can sensitively sense complex external stimuli of pressure, strain, temperature, and localization. The OE skin consists of elastic thin polymer-stabilized cholesteric liquid crystal films, an ion-conductive hydrogel layer, and an elastic protective membrane formed with thin polydimethylsiloxane. The as-designed OE skin exhibits customizable structural color on demand, good thermochromism, and excellent mechanochromism, with the ability to extend the full visible spectrum, a good linearity of over 0.99, fast response speed of 93 ms, and wide temperature range of 119 °C. In addition, the conduction resistance variation of ion-conductive hydrogel exhibits excellent sensing capabilities under pressure, stretch, and temperature, endowing a good linearity of 0.99998 (stretching from 0 to 150%) and high thermal sensitivity of 0.86% per °C. Such an outstanding OE skin provides design concepts for the development of multifunctional biomimetic skin used in human-machine interaction and can find wide applications in intelligent wearable devices and human-machine interactions.

Triaryl Carbenium Ion Pair Mediated Electrocatalytic Benzylic C-H Oxygenation in Air.

The selective oxidation of benzylic C-H bonds is a pivotal transformation in organic synthesis. Undoubtedly, achieving efficient and highly selective aerobic oxidation of methylarenes to benzaldehydes has been highly challenging due to the propensity of benzaldehyde to undergo overoxidation under typical aerobic conditions. Herein, we propose an innovative approach to address this issue by leveraging electrocatalytic processes, facilitated by ion-pair mediators [Ph3C]+[B(C6F5)4]-. By harnessing the power of electrochemistry, we successfully demonstrated the effectiveness of our strategy, which enables the selective oxidation of benzylic C-H bonds in benzylic molecules and toluene derivatives. Notably, our approach exhibited high efficiency, excellent selectivity, and compatibility with various functional groups, underscoring the broad applicability of our methodology.

Rapid discrimination of four Salmonella enterica serovars: A performance comparison between benchtop and handheld Raman spectrometers.

Foodborne illnesses, particularly those caused by Salmonella enterica with its extensive array of over 2600 serovars, present a significant public health challenge. Therefore, prompt and precise identification of S. enterica serovars is essential for clinical relevance, which facilitates the understanding of S. enterica transmission routes and the determination of outbreak sources. Classical serotyping methods via molecular subtyping and genomic markers currently suffer from various limitations, such as labour intensiveness, time consumption, etc. Therefore, there is a pressing need to develop new diagnostic techniques. Surface-enhanced Raman spectroscopy (SERS) is a non-invasive diagnostic technique that can generate Raman spectra, based on which rapid and accurate discrimination of bacterial pathogens could be achieved. To generate SERS spectra, a Raman spectrometer is needed to detect and collect signals, which are divided into two types: the expensive benchtop spectrometer and the inexpensive handheld spectrometer. In this study, we compared the performance of two Raman spectrometers to discriminate four closely associated S. enterica serovars, that is, S. enterica subsp. enterica serovar dublin, enteritidis, typhi and typhimurium. Six machine learning algorithms were applied to analyse these SERS spectra. The support vector machine (SVM) model showed the highest accuracy for both handheld (99.97%) and benchtop (99.38%) Raman spectrometers. This study demonstrated that handheld Raman spectrometers achieved similar prediction accuracy as benchtop spectrometers when combined with machine learning models, providing an effective solution for rapid, accurate and cost-effective identification of closely associated S. enterica serovars.

Molecular insights into the catabolism of dibutyl phthalate in Pseudomonas aeruginosa PS1 based on biochemical and multi-omics approaches.

A comprehensive understanding of the molecular mechanisms underlying microbial catabolism of dibutyl phthalate (DBP) is still lacking. Here, we newly isolated a bacterial strain identified as Pseudomonas aeruginosa PS1 with high efficiency of DBP degradation. The degradation ratios of DBP at 100-1000 mg/L by this strain reached 80-99 % within 72 h without a lag phase. A rare DBP-degradation pathway containing two monobutyl phthalate-catabolism steps was proposed based on intermediates identified by HPLC-TOF-MS/MS. In combination with genomic and transcriptomic analyses, we identified 66 key genes involved in DBP biodegradation and revealed the genetic basis for a new complete catabolic pathway from DBP to Succinyl-CoA or Acetyl-CoA in the genus Pseudomonas for the first time. Notably, we found that a series of homologous genes in Pht and Pca clusters were simultaneously activated under DBP exposure and some key intermediate degradation related gene clusters including Pht, Pca, Xyl, Ben, and Cat exhibited a favorable coexisting pattern, which contributed the high-efficient DBP degradation ability and strong adaptability to this strain. Overall, these results broaden the knowledge of the catabolic diversity of DBP in microorganisms and enhance our understanding of the molecular mechanism underlying DBP biodegradation.

Structural insights into Xanthomonas campestris pv. campestris NAD+ biosynthesis via the NAM salvage pathway.

Nicotinamide phosphoribosyltransferase (NAMPT) plays an important role in the biosynthesis of nicotinamide adenine dinucleotide (NAD+) via the nicotinamide (NAM) salvage pathway. While the structural biochemistry of eukaryote NAMPT has been well studied, the catalysis mechanism of prokaryote NAMPT at the molecular level remains largely unclear. Here, we demonstrated the NAMPT-mediated salvage pathway is functional in the Gram-negative phytopathogenic bacterium Xanthomonas campestris pv. campestris (Xcc) for the synthesis of NAD+, and the enzyme activity of NAMPT in this bacterium is significantly higher than that of human NAMPT in vitro. Our structural analyses of Xcc NAMPT, both in isolation and in complex with either the substrate NAM or the product nicotinamide mononucleotide (NMN), uncovered significant details of substrate recognition. Specifically, we revealed the presence of a NAM binding tunnel that connects the active site, and this tunnel is essential for both catalysis and inhibitor binding. We further demonstrated that NAM binding in the tunnel has a positive cooperative effect with NAM binding in the catalytic site. Additionally, we discovered that phosphorylation of the His residue at position 229 enhances the substrate binding affinity of Xcc NAMPT and is important for its catalytic activity. This work reveals the importance of NAMPT in bacterial NAD+ synthesis and provides insights into the substrate recognition and the catalytic mechanism of bacterial type II phosphoribosyltransferases.

Triphenyltin induced darker body coloration by disrupting melanocortin system and pteridine metabolic pathway in a reef fish, Amphiprion ocellaris.

Triphenyltin (TPT) is a typical persistent organic pollutant whose occurrence in coral reef ecosystems may threaten the survival of reef fishes. In this study, a brightly colored representative reef fish, Amphiprion ocellaris was used to explore the effects of TPT at environmental levels (1, 10, and 100 ng/L) on skin pigment synthesis. After the fish were exposed to TPT for 60 days, the skin became darker, owing to an increase in the relative area of black stripes, a decrease in orange color values while an increase in brown color values, and an increase in the number of melanocytes in the orange part of the skin tissues. To explore the mechanisms by which TPT induces darker body coloration, the enzymatic activity and gene expression levels of the members of melanocortin system that affect melanin synthesis were evaluated. Leptin levels and lepr expression were found to be increased after TPT exposure, which likely contributed to the increase found in pomc expression and α-melanocyte-stimulating hormone (α-MSH) levels. Then Tyr activity and mc1r, tyr, tyrp1, mitf, and dct were upregulated, ultimately increasing melanin levels. Importantly, RT-qPCR results were consistent with the transcriptome analysis of trends in lepr and pomc expression. Because the orange color values decreased, pterin levels and the pteridine metabolic pathway were also evaluated. The results showed that TPT induced BH4 levels and spr, xdh, and gch1 expression associated with pteridine synthesis decreased, ultimately decreasing the colored pterin content (sepiapterin). We conclude that TPT exposure interferes with the melanocortin system and pteridine metabolic pathway to increase melanin and decrease colored pterin levels, leading to darker body coloration in A. ocellaris. Given the importance of body coloration for the survival and reproduction of reef fishes, studies on the effects of pollutants (others alongside TPT) on body coloration are of high priority.

Periodontal disease in patients with WHIM syndrome.

AIM: WHIM (warts, hypogammaglobulinaemia, infections and myelokathexis) syndrome is a rare combined primary immunodeficiency disease caused by gain-of-function (GOF) mutations in the chemokine receptor CXCR4 and includes severe neutropenia as a common feature. Neutropenia is a known risk factor for periodontitis; however, a detailed periodontal evaluation of a WHIM syndrome cohort is lacking. This study aimed to establish the evidence base for the periodontal status of patients with WHIM syndrome. MATERIALS AND METHODS: Twenty-two adult WHIM syndrome patients and 22 age- and gender-matched healthy volunteers (HVs) were evaluated through a comprehensive medical and periodontal examination. A mouse model of WHIM syndrome was assessed for susceptibility to naturally progressing or inducible periodontitis. RESULTS: Fourteen patients with WHIM syndrome (63.6%) and one HV (4.5%) were diagnosed with Stage III/IV periodontitis. No WHIM patient presented with the early onset, dramatic clinical phenotypes typically associated with genetic forms of neutropenia. Age, but not the specific CXCR4 mutation or absolute neutrophil count, was associated with periodontitis severity in the WHIM cohort. Mice with a Cxcr4 GOF mutation did not exhibit increased alveolar bone loss in spontaneous or ligature-induced periodontitis. CONCLUSIONS: Overall, WHIM syndrome patients presented with an increased severity of periodontitis despite past and ongoing neutrophil mobilization treatments. GOF mutations in CXCR4 may be a risk factor for periodontitis in humans.

Synergistic Effect of Ion Doping and Type-II Heterojunction Construction and Ciprofloxacin Degradation by MIL-68(In,Bi)-NH2@BiOBr under Visible Light.

Heterojunction structure and ion doping techniques are viable tactics in facilitating the generation and separation of photogenerated electrons and holes in photocatalysis. In the current study, a novel Bi ion-doped MIL-68(In,Bi)-NH2@BiOBr (MIBN@BOB) type-II heterojunction was first synthesized in a one-step solvothermal reaction. Doping of Bi ions not only broadened the light-sensing range but also provided reliable anchor sites for the in situ growth of BiOBr. Meanwhile, the heterostructure supplied new channels for photogenerated carriers, accelerating the transfer and inhibiting the recombination of photogenerated electron-hole. The obtained MIBN@BOB exhibited enhanced photocatalytic performance (91.1%) than MIL-68(In)-NH2 (40.8%) and BiOBr (57.5%) in ciprofloxacin (CIP) degradation under visible light, with excellent reusability. Photocatalysts were characterized in detail, and a series of photoelectrochemical tests were utilized to analyze the photoelectric properties. MIBN@BOB were deduced to conform the electron conduction mechanism of conventional type-II heterojunctions. More importantly, based on the above experiments and density functional theory (DFT) calculation, BiOBr-Bi in MIBN@BOB can serve as the major active sites of CIP enrichment, and •O2- and 1O2 generated at the BiOBr interface can react with the adsorbed CIP directly. Lastly, the possible degradation products and pathways of CIP were analyzed by liquid chromatography-tandem mass spectrometry (LC/MS/MS). This study provides a reference for the construction of ion-doping-modified metal-organic framework (MOF)-based heterojunction photocatalysts and their application in antibiotic removal.

A universal synthesis strategy of Pd-based trimetallic nanowires for efficient alcohol electrooxidation.

Trimetallic nanowires (NWs) have drawn much attention in efficient alcohol oxidation reaction (AOR) due to their unique features, including high atomic utilization efficiency and fast electron transfer ability. However, a universal strategy to synthesize Pd-based trimetallic NWs with high catalytic performance is still lacking. Herein, we develop a universal method for facile synthesis of PdBiM (M = Pt, Ru, Ir, Co, Cu) NWs with excellent AOR activities. By taking PdBiPt NWs as an example, the formation mechanism was investigated, and it is found that introduction of bismuth (Bi) plays an important role in facilitating the formation of the NW structure. Moreover, the PdBiPt NWs deliver an outstanding performance toward both the ethanol oxidation reaction (EOR) and the methanol oxidation reaction (MOR). Density functional theory (DFT) calculations together with experimental results disclose that the moderate electronic structure of trimetallic PdBiPt NWs can optimize the adsorption of OHads and weaken the adsorption of COads, thereby leading to the substantially enhanced AOR performance. We believe that this work can inspire the design of multimetallic NWs as high-performance catalysts.

Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells.

OBJECTIVE: To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification. METHODS: Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway. RESULTS: The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G1-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway. CONCLUSION: Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.

Tranexamic acid is not associated with a higher rate of thrombotic-related reintervention after major vascular injury repair.

BACKGROUND: Tranexamic acid (TXA) is associated with lower mortality and transfusion requirements in trauma patients, but its role in thrombotic complications associated with vascular repairs remains unclear. We investigated whether TXA increases the risk of thrombosis-related technical failure (TRTF) in major vascular injuries (MVI). METHODS: The PROspective Observational Vascular Injury Treatment (PROOVIT) registry was queried from 2013 to 2022 for MVI repaired with an open or endovascular intervention. The relationship between TXA administration and TRTF was examined. RESULTS: The TXA group (n = 297) had higher rates of hypotension at admission (33.6% vs. 11.5%, p < 0.001), need for continuous vasopressors (41.4% vs. 18.4%, p < 0.001), and packed red blood cell transfusion (3.2 vs. 2.0 units, p < 0.001) during the first 24 hours compared with the non-TXA group (n = 1941), although demographics, injury pattern, and interventions were similar. Cryoprecipitate (9.1% vs. 2%, p < 0.001), and anticoagulant administration during the intervention (32.7% vs. 43.8%, p < 0.001) were higher in the TXA group; there was no difference in the rate of factor VII use between groups (1% vs. 0.7%, p = 0.485). Thrombosis-related technical failure was not different between the groups (6.3% vs. 3.8 p = 0.141) while the rate of immediate need for reoperation (10.1% vs. 5.7%, p = 0.006) and overall reoperation (11.4% vs. 7%, p = 0.009) was significantly higher in the TXA group on univariate analysis. There was no significant association between TXA and a higher rate of immediate need for reintervention (odds ratio [OR], 1.19; 95% confidence interval [CI], 0.75-1.88; p = 0.465), overall reoperation rate (OR, 1.33; 95% CI, 0.82-2.17; p = 0.249) and thrombotic events in a repaired vessel (OR, 1.07; 95% CI, 0.60-1.92; p = 0.806) after adjusting for type of injury, vasopressor infusions, blood product and anticoagulant administration, and hemodynamics. CONCLUSION: Tranexamic acid is not associated with a higher risk of thrombosis-related technical failure in traumatic injuries requiring major vascular repairs. Further prospective studies to examine dose-dependent or time-dependent associations between TXA and thrombotic events in MVIs are needed. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells / 中国结合医学杂志

OBJECTIVE@#To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification.@*METHODS@#Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway.@*RESULTS@#The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G1-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway.@*CONCLUSION@#Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.

A cross-sectional study of contraceptive use and healthcare status among women at different times in the postpartum period / 上海预防医学

ObjectiveTo investigate the use of contraceptive methods， and to evaluate maternal healthcare services utilization among women within 2 years in Pudong New Area of Shanghai. MethodsA cross-sectional survey was conducted using a questionnaire for women at different postpartum periods who visited a community health clinic with their children from June to November 2021. Data were analyzed using χ2 test and binary logistic regression. ResultsAmong the 1 946 postpartum women surveyed， 1 934 were either married or cohabiting， and1 430 had resumed their sexual life. Among women at 4， 6， 12， 18 and 24 months postpartum， the contraceptive prevalence rates （CPR） were 92.34% （193/209）， 92.16% （235/255）， 87.31% （282/323）， 91.95% （297/323） and 90.00% （288/320）， respectively. The modern contraceptive prevalence rates （mCPR） were 87.08% （182/209）， 87.06% （222/255）， 82.04% （265/323）， 83.09% （271/323） and 85.31% （273/320）， respectively， while the unmet contraceptive needs （UMNs） were 7.66% （16/209）， 7.84% （20/255）， 11.46% （37/323）， 6.81% （22/323） and 10.00% （32/320）， respectively. The use rates of long-acting reversible contraceptive （LARC） methods among women at 6， 12， 18 and 24 months postpartum period were 0.39% （1/255）， 2.17% （7/323）， 0.31% （1/323）， and 2.81% （9/320）， respectively. Among all surveyed subjects， 32.17% （626/1 946） had received postpartum contraceptive services only once， while 27.85% （542/1 946） had not received any postpartum contraceptive services. Binary logistic regression analysis indicated that the use of contraceptive methods among postpartum women was associated with whether relevant educational services were received after childbirth and during postpartum home visits （all P<0.05）. ConclusionPostpartum women have unmet needs for contraception. Contraceptive guidance at the 42-day postnatal healthcare visit needs to be further strengthened and postpartum contraceptive education could be integrated into the pregnancy care. The quality and effectiveness of contraceptive education during delivery and postpartum home visits， and even at the 42-day postnatal healthcare visit need to be further explored.

Insights into the molecular network underlying phytotoxicity and phytoaccumulation of ciprofloxacin.

Ciprofloxacin (CIP) is frequently detected in agricultural soils and can be accumulated by crops, causing phytotoxicities and food safety concerns. However, the molecular basis of its phytotoxicity and phytoaccumulation is hardly known. Here, we analyzed physiological and molecular responses of choysum (Brassica parachinensis) to CIP stress by comparing low CIP accumulation variety (LAV) and high accumulation variety (HAV). Results showed that the LAV suffered more severe inhibition of growth and photosynthesis than the HAV, exhibiting a lower tolerance to CIP toxicity. Integrated transcriptome and proteome analyses suggested that more differentially expressed genes/proteins (DEGs/DEPs) involved in basic metabolic processes were downregulated to a larger extent in the LAV, explaining its lower CIP tolerance at molecular level. By contrast, more DEGs/DEPs involved in defense responses were upregulated to a larger extent in the HAV, showing the molecular basis of its stronger CIP tolerance. Further, a CIP phytotoxicity-responsive molecular network was constructed for the two varieties to better understand the molecular mechanisms underlying the variety-specific CIP tolerance and accumulation. The results present the first comprehensive molecular profile of plant response to CIP stress for molecular-assisted breeding to improve CIP tolerance and minimize CIP accumulation in crops.

[Analysis of influence of MR signs on Harris score in ARCO stages 2-4 femoral head necrosis].

OBJECTIVE: To analysis and determine MR signs of Harris score ARCO stages 2-4 in osteonecrosis of femoral head (ONFH). METHODS: Thirty-four patients with ONFH of ARCO stages 2 to 4 who underwent routine MR, T2 mapping, 3D-SPACE sequence examination and Harris score were retrospectively collected from January 2019 to June 2020, and 3 patients were excluded, and 31 patients were finally included, including 23 males and 8 females, aged from 18 to 62 years old with an average of(40.0±10.8) years old. Among them 21 patients with bilateral femoral head necrosis, totally 52 cases, including 17 with ARCO stage 2 patients, 24 ARCO stage 3, and 11 ARCO stage 4. MR imaging signs (femoral head collapse depth, ONFH index, bone marrow edema, hyperplasia, grade and T2 value of cartilage injury, and joint effusion) were scored and measured on the picture archiving and communication system (PACS) workstation, and the cartilage quantitative parameter T2 value was calculated and measured on Siemens postprocessing workstation. Pearson correlation analysis was used to evaluate the correlation between various MR signs and Harris score, and then multiple linear regression analysis was used to examine impact of MR signs on Harris hip score. RESULTS: Femoral head collapse depth(r=-0.563, P=0.000), grade of cartilage injury(r=-0.500, P=0.000), and joint effusion (r=-0.535, P=0.000) were negatively correlated with Harris score by Pearson correlation analysis. Multiple linear regression analysis showed that joint effusion(ß=-6.198, P=0.001) and femoral head collapse depth(ß=-4.085, P=0.014) had a significant negative impact on Harris hip score. CONCLUSION: Femoral head collapse depth and joint effusion both had significant negative relationship with Harris hip score. It is recommended to routinely evaluate femoral head collapse depth and joint effusion quantitatively and gradedly, so as to efficiently and accurately assist clinical diagnosis and treatment.

NAD+ rescues aging-induced blood-brain barrier damage via the CX43-PARP1 axis.

Blood-brain barrier (BBB) function deteriorates during aging, contributing to cognitive impairment and neurodegeneration. It is unclear what drives BBB leakage in aging and how it can be prevented. Using single-nucleus transcriptomics, we identified decreased connexin 43 (CX43) expression in cadherin-5+ (Cdh5+) cerebral vascular cells in naturally aging mice and confirmed it in human brain samples. Global or Cdh5+ cell-specific CX43 deletion in mice exacerbated BBB dysfunction during aging. The CX43-dependent effect was not due to its canonical gap junction function but was associated with reduced NAD+ levels and mitochondrial dysfunction through NAD+-dependent sirtuin 3 (SIRT3). CX43 interacts with and negatively regulates poly(ADP-ribose) polymerase 1 (PARP1). Pharmacologic inhibition of PARP1 by olaparib or nicotinamide mononucleotide (NMN) supplementation rescued NAD+ levels and alleviated aging-associated BBB leakage. These findings establish the endothelial CX43-PARP1-NAD+ pathway's role in vascular aging and identify a potential therapeutic strategy to combat aging-associated BBB leakage with neuroprotective implications.

Rationally Designed Enzyme-Resistant Peptidic Assemblies for Plasma Membrane Targeting in Cancer Treatment.

Peptides are being increasingly important for subcellular targeted cancer treatment to improve specificity and reverse multidrug resistance. However, there has been yet any report on targeting plasma membrane (PM) through self-assembling peptides. A simple synthetic peptidic molecule (tF4) is developed. It is revealed that tF4 is carboxyl esterase-resistant and self-assembles into vesical nanostructures. Importantly, tF4 assemblies interact with PM through orthogonal hydrogen bonding and hydrophobic interaction to regulate cancer cellular functions. Mechanistically, tF4 assemblies induce stress fiber formation, cytoskeleton reconstruction, and death receptor 4/5 (DR4/5) expression in cancer cells. DR4/5 triggers extrinsic caspase-8 signaling cascade, resulting in cell death. The results provide a new strategy for developing enzyme-resistant and PM-targeting peptidic molecules against cancer.