Immobilization of the Polar Group into an Ultramicroporous Metal-Organic Framework Enabling Benchmark Inverse Selective CO2/C2H2 Separation with Record C2H2 Production.

One-step harvest of high-purity light hydrocarbons without the desorption process represents an advanced and highly efficient strategy for the purification of target substances. The separation and purification of acetylene (C2H2) from carbon dioxide (CO2) by CO2-selective adsorbents are urgently demanded yet are very challenging owing to their similar physicochemical properties. Here, we employ the pore chemistry strategy to adjust the pore environment by immobilizing polar groups into an ultramicroporous metal-organic framework (MOF), achieving one-step manufacture of high-purity C2H2 from CO2/C2H2 mixtures. Embedding methyl groups into prototype stable MOF (Zn-ox-trz) not only changes the pore environment but also improves the discrimination of guest molecules. The methyl-functionalized Zn-ox-mtz thus exhibits the benchmark reverse CO2/C2H2 uptake ratio of 12.6 (123.32/9.79 cm3 cm-3) and an exceptionally high equimolar CO2/C2H2 selectivity of 1064.9 at ambient conditions. Molecular simulations reveal that the synergetic effect of pore confinement and surfaces decorated with methyl groups provides high recognition of CO2 molecules through multiple van der Waals interactions. The column breakthrough experiments suggest that Zn-ox-mtz dramatically achieved the one-step purification capacity of C2H2 from the CO2/C2H2 mixture with a record C2H2 productivity of 2091 mmol kg-1, surpassing all of the CO2-selective adsorbents reported so far. In addition, Zn-ox-mtz exhibits excellent chemical stability under different pH values of aqueous solutions (pH = 1-12). Moreover, the highly stable framework and excellent inverse selective CO2/C2H2 separation performance showcase its promising application as a C2H2 splitter for industrial manufacture. This work paves the way to developing reverse-selective adsorbents for the challenging gas separation process.

Single-cell transcriptome reveals Staphylococcus aureus modulating fibroblast differentiation in the bone-implant interface.

BACKGROUND: This study aimed to delineate the cell heterogeneity in the bone-implant interface and investigate the fibroblast responses to implant-associated S. aureus infection. METHODS: Single-cell RNA sequencing of human periprosthetic tissues from patients with periprosthetic joint infection (PJI, n = 3) and patients with aseptic loosening (AL, n = 2) was performed. Cell type identities and gene expression profiles were analyzed to depict the single-cell landscape in the periprosthetic environment. In addition, 11 publicly available human scRNA-seq datasets were downloaded from GSE datasets and integrated with the in-house sequencing data to identify disease-specific fibroblast subtypes. Furthermore, fibroblast pseudotime trajectory analysis and Single-cell regulatory network inference and clustering (SCENIC) analysis were combined to identify transcription regulators responsible for fibroblast differentiation. Immunofluorescence was performed on the sequenced samples to validate the protein expression of the differentially expressed transcription regulators. RESULTS: Eight major cell types were identified in the human bone-implant interface by analyzing 36,466 cells. Meta-analysis of fibroblasts scRNA-seq data found fibroblasts in the bone-implant interface express a high level of CTHRC1. We also found fibroblasts could differentiate into pro-inflammatory and matrix-producing phenotypes, each primarily presented in the PJI and AL groups, respectively. Furthermore, NPAS2 and TFEC which are activated in PJI samples were suggested to induce pro-inflammatory polarization in fibroblasts, whereas HMX1, SOX5, SOX9, ZIC1, ETS2, and FOXO1 are matrix-producing regulators. Meanwhile, we conducted a CMap analysis and identified forskolin as a potential regulator for fibroblast differentiation toward matrix-producing phenotypes. CONCLUSIONS: In this study, we discovered the existence of CTHRC1+ fibroblast in the bone-implant interface. Moreover, we revealed a bipolar mode of fibroblast differentiation and put forward the hypothesis that infection could modulate fibroblast toward a pro-inflammatory phenotype through NPAS2 and TFEC.

Combined Use of Tumor Markers in Gastric Cancer: A Novel Method with Promising Prognostic Accuracy and Practicality.

BACKGROUND: The effect of a single tumor marker on the prognosis of gastric cancer patients is not ideal. This study explored a novel prognostic assessment method for gastric cancer (GC) patients using a combination of three important tumor markers (CEA, CA72-4, and CA19-9). METHOD: Data from 1966 GC patients who underwent curative gastrectomy at Sun Yat-Sen University Cancer Center (Guangzhou, China) were included. Hazard ratios (HR) for all factors for overall survival (OS) were analyzed by Cox regression. A nomogram and calibration curve were used to establish the survival prediction model. The prediction accuracy was evaluated with the concordance index (C-index). RESULTS: All patients were divided into four groups (C0-C3) according to the number of elevated tumor markers. The 5-year OS rates of the patients in preoperative groups C0-C3 were 83.8% (81.3-86.4%), 72.8% (68.5-77.4%), 58.9% (50.4-68.9%), and 18.5% (4.0-33.0%), respectively, and those in postoperative groups C0-C3 were 82.1% (79.4-84.8%), 76.1% (72.2-80.3%), 57.6% (48.4-68.5%), and 16.8% (5.1-28.5%), respectively, with significant differences between each C0-C3 subgroup in both preoperative and postoperative cohorts. Multivariate analysis showed that preoperative (HR: 6.001, 95% CI: 3.523-10.221) and postoperative (HR: 8.149, 95% CI: 4.962-13.528) elevated tumor markers were independent risk factors for GC patients. The C-index for the combined use of tumor markers was 0.65-0.66, which was higher than that for using a single tumor marker (0.53-0.56). CONCLUSION: The combined use of tumor markers significantly improved the prognostic value compared with using a single tumor marker. The survival prediction model including the combined tumor markers was accurate and effective.

Adjuvant Chemotherapy for Patients with Adenocarcinoma of the Esophagogastric Junction: A Retrospective, Multicenter, Observational Study.

BACKGROUND: Although the incidence of adenocarcinoma of the esophagogastric junction (AEG) has been increasing since the past decade, the proportion of AEG cases in two previous clinical trials (ACTS-GC and CLASSIC) that investigated the efficacy of adjuvant chemotherapy was relatively small. Therefore, whether AEG patients can benefit from adjuvant chemotherapy remains unclear. METHODS: Patients who were diagnosed with pathological stage II/III, Siewert II/III AEG, and underwent curative surgery at three high-volume institutions were assessed. Clinical outcomes were analyzed by using Kaplan-Meier curves, log-rank test, and Cox regression model. Propensity score matching (PSM) was used to reduce the selection bias. RESULTS: A total of 927 patients were included (the chemotherapy group: 696 patients; the surgery-only group: 231 patients). The median follow-up was 39.0 months. The 5-year overall survival was 63.1% (95% confidence interval [CI]: 59.0-67.6%) for the chemotherapy group and 50.2% in the surgery-only group (hazard ratio [HR] = 0.69, 95% CI: 0.54-0.88; p = 0.003). The 5-year, disease-free survival was 35.4% for the chemotherapy group and 16.6% for the surgery-only group (HR = 0.66, 95% CI: 0.53-0.83; p < 0.001). After PSM, the survival benefit of adjuvant chemotherapy for AEG was maintained. Multivariate analysis for overall survival and disease-free survival further demonstrated the survival benefit of adjuvant chemotherapy, with HRs of 0.63 (p < 0.001) and 0.52 (p < 0.001), respectively. CONCLUSIONS: Postoperative adjuvant chemotherapy was associated with improved overall survival and disease-free survival in patients with operable stage II or III AEG after D2 gastrectomy.

Function analysis of choline binding domains (CBDs) of LytA, LytC and CbpD in biofilm formation of Streptococcus pneumoniae.

Biofilm formation is an important strategy for the colonization of Streptococcus pneumoniae, which can increase the capacity to evade antibiotic and host immune stress. Extracellular choline-binding proteins (CBPs) are required for successful biofilm formation, but the function of extracellular CBPs in the process of biofilm formation is not fully understood. In this study, we tend to analyze the functions of LytA, LytC and CbpD in biofilm formation by in vitro studies with their choline-binding domains (CBDs). Biofilm formation of S. pneumoniae was enhanced when cultured in medium supplemented with CBD-C and CBD-D. Parallel assays with ChBp-Is (choline binding repeats with different C-terminal tails) and character analysis of CBDs reveal a higher isoelectric point (pI) is related to promotion of biofilm formation. Phenotype characterization of biofilms revel CBD-C and CBD-D function differently, CBD-C promoting the formation of membrane-like structures and CBD-D promoting the formation of regular reticular structures. Gene expression analysis reveals membrane transport pathways are influenced with the binding of CBDs, among which the phosphate uptake and PTS of galactose pathways are both up-regulated under conditions with CBDs. Further, extracellular substances detection revealed that extracellular proteins increased with CBD-A and CBD-D, exhibiting as increase in extracellular high molecular weight proteins. Extracellular DNA increased under CBD-A but decreased under CBD-C and CBD-D; Extracellular phosphate increased under CBD-C. These support the alterations in membrane transport pathways, and reveal diverse reactions to extracellular protein, DNA and phosphate of these three CBDs. Overall, our results indicated extracellular CBP participate in biofilm formation by affecting surface charge and membrane transport pathways of pneumococcal cells, as well as promoting reactions to extracellular substances.

Fungi-enabled pore channel regulation and defect engineering of a novel micro-reactor for treating complex effluents.

Defect engineering has become a significant research area in recent years; however, little has been reported on the biological method for modulating the intrinsic carbon defects of the biochar framework. Herein, a fungi-enabled method for the fabrication of porous carbon/Fe3O4/Ag (PC/Fe3O4/Ag) composites was developed, and the mechanism underlying the hierarchical structure is elucidated for the first time. By regulating the cultivation process of fungi on water hyacinth biomass, a well-developed interconnected structure and carbon defects acting as potential catalytic active sites were formed. This new material with antibacterial, adsorption and photodegradation properties could be an excellent choice for treating the mixed dyestuff effluents with oils and bacteria, also guiding pore channel regulation and defect engineering in materials science. Numerical simulations were carried out to demonstrate the remarkable catalytic activity.

α-Synuclein Selectively Impairs Motor Sequence Learning and Value Sensitivity: Reversal by the Adenosine A2A Receptor Antagonists.

Parkinson's disease (PD) is characterized pathologically by alpha-synuclein (α-Syn) aggregates and clinically by the motor as well as cognitive deficits, including impairments in sequence learning and habit learning. Using intracerebral injection of WT and A53T mutant α-Syn fibrils, we investigate the behavioral mechanism of α-Syn for procedure-learning deficit in PD by critically determining the α-Syn-induced effects on model-based goal-directed behavior, model-free (probability-based) habit learning, and hierarchically organized sequence learning. 1) Contrary to the widely held view of habit-learning deficit in early PD, α-Syn aggregates in the dorsomedial striatum (DMS) and dorsolateral striatum (DLS) did not affect acquisition of habit learning, but selectively impaired goal-directed behavior with reduced value sensitivity. 2) α-Syn in the DLS (but not DMS) and SNc selectively impaired the sequence learning by affecting sequence initiation with the reduced first-step accuracy. 3) Adenosine A2A receptor (A2AR) antagonist KW6002 selectively improved sequence learning by preferentially improving sequence initiation and shift of sequence learning as well as behavioral reactivity. These findings established a casual role of α-Syn in the SN-DLS pathway in sequence-learning deficit and DMS α-Syn in goal-directed behavior deficit and suggest a novel therapeutic strategy to improve sequence-learning deficit in PD with enhanced sequence initiation by A2AR antagonists.

α-Synuclein Aggregates in the Nigro-Striatal Dopaminergic Pathway Impair Fine Movement: Partial Reversal by the Adenosine A2A Receptor Antagonist.

Parkinson's disease (PD) is characterized pathologically by abnormal aggregation of alpha-synuclein (α-Syn) in the brain and clinically by fine movement deficits at the early stage, but the roles of α-Syn and associated neural circuits and neuromodulator bases in the development of fine movement deficits in PD are poorly understood, in part due to the lack of appropriate behavioral testing paradigms and PD models without motor confounding effects. Here, we coupled two unique behavioral paradigms with two PD models to reveal the following: (i) Focally injecting α-Syn fibrils into the dorsolateral striatum (DLS) and the transgenic expression of A53T-α-Syn in the dopaminergic neurons in the substantia nigra (SN, PITX3-IRES2-tTA/tetO-A53T mice) selectively impaired forelimb fine movements induced by the single-pellet reaching task. (ii) Injecting α-Syn fibers into the SN suppressed the coordination of cranial and forelimb fine movements induced by the sunflower seed opening test. (iii) Treatments with the adenosine A2A receptor (A2AR) antagonist KW6002 reversed the impairment of forelimb and cranial fine movements induced by α-Syn aggregates in the SN. These findings established a causal role of α-Syn in the SNc-DLS dopaminergic pathway in the development of forelimb and cranial fine movement deficits and suggest a novel therapeutic strategy to improve fine movements in PD by A2AR antagonists.

Carbapenem-resistant K. pneumoniae exhibiting clinically undetected amikacin and meropenem heteroresistance leads to treatment failure in a murine model of infection.

Heteroresistance is a poorly understood mechanism of resistance which refers to a phenomenon where there are different subpopulations of seemingly isogenic bacteria which exhibit a range of susceptibilities to a particular antibiotic. In the current study, we identified a multidrug-resistant, carbapenemase-positive K. pneumoniae strain SWMUF35 which was classified as susceptible to amikacin and resistant to meropenem by clinical diagnostics yet harbored different subpopulations of phenotypically resistant cells, and has the ability to form biofilm. Population analysis profile (PAP) indicated that SWMUF35 showed heteroresistance towards amikacin and meropenem which was considered as co-heteroresistant K. pneumoniae strain. In vitro experiments such as dual PAP, dual Times-killing assays and checkerboard assay showed that antibiotic combination therapy (amikacin combined with meropenem) can effectively combat SWMUF35. Importantly, using an in vivo mouse model of peritonitis, we found that amikacin or meropenem monotherapy was unable to rescue mice infected with SWMUF35. Antibiotic combination therapy could be a rational strategy to use clinically approved antibiotics when monotherapy would fail. Furthermore, our data warn that antibiotic susceptibility testing results may be unreliable due to undetected heteroresistance which can lead to treatment failure and the detection of this phenotype is a prerequisite for a proper choice of antibiotic to support a successful treatment outcome.

Design of an Integrated Remote and Ground Sensing Monitor System for Assessing Farmland Quality.

Quality monitoring is important for farmland protection. Here, high-resolution remote sensing data obtained by unmanned aerial vehicles (UAVs) and long-term ground sensing data, obtained by wireless sensor networks (WSNs), are uniquely suited for assessing spatial and temporal changes in farmland quality. However, existing UAV-WSN systems are unable to fully integrate the data obtained from these two monitoring systems. This work addresses this problem by designing an improved UAV-WSN monitoring system that can collect both high-resolution UAV images and long-term WSN data during a single-flight mission. This is facilitated by a newly proposed data transmission optimization routing protocol (DTORP) that selects the communication node within a cluster of the WSN to maximize the quantity of data that can be efficiently transmitted, additionally combining individual scheduling algorithms and routing algorithms appropriate for three different distance scales to reduce the energy consumption incurred during data transmission between the nodes in a cluster. The performance of the proposed system is evaluated based on Monte Carlo simulations by comparisons with that obtained by a conventional system using the low-energy adaptive clustering hierarchy (LEACH) protocol. The results demonstrate that the proposed system provides a greater total volume of transmitted data, greater energy utilization efficiency, and a larger maximum revisit period than the conventional system. This implies that the proposed UAV-WSN monitoring system offers better overall performance and enhanced potential for conducting long-term farmland quality data collection over large areas in comparison to existing systems.

A review on drone-based harmful algae blooms monitoring.

Rapid development and applications of unmanned aerial vehicles (UAVs) provide promising solutions to and new opportunities for environmental monitoring. Owing to their flexibility in flight scheduling, high spatial resolution, and costs-effectiveness, UAVs have become a popular tool for monitoring dynamic environmental processes, such as emergence and outbreak of harmful algae blooms (HABs). The HABs outbreak, often linked with anthropogenic eutrophication, has become a serious environmental health problem that threats our communities. Existing studies show that UAV-based HABs monitoring is a cost-effective means of assisting environmental managers in developing precautionary warning system and coping strategies. This article summarized the state-of-the-art of using UAVs and lightweight onboard multispectral sensors for HABs monitoring from the perspective of quantitative remote sensing. It culminates in a discussion of challenges and opportunities for future research and applications on drone-based HABs monitoring.

Preparation and corrosion resistance of magnesium phytic acid/hydroxyapatite composite coatings on biodegradable AZ31 magnesium alloy.

In this work, a magnesium phytic acid/hydroxyapatite composite coating was successfully prepared on AZ31 magnesium alloy substrate by chemical conversion deposition technology with the aim of improving its corrosion resistance and bioactivity. The influence of hydroxyapatite (HA) content on the microstructure and corrosion resistance of the coatings was investigated. The results showed that with the increase of HA content in phytic acid solution, the cracks on the surface of the coatings gradually reduced, which subsequently improved the corrosion resistance of these coated magnesium alloy. Electrochemical measurements in simulated body fluid (SBF) revealed that the composite coating with 45 wt.% HA addition exhibited superior surface integrity and significantly improved corrosion resistance compared with the single phytic acid conversion coating. The results of the immersion test in SBF showed that the composite coating could provide more effective protection for magnesium alloy substrate than that of the single phytic acid coating and showed good bioactivity. Magnesium phytic acid/hydroxyapatite composite, with the desired bioactivity, can be synthesized through chemical conversion deposition technology as protective coatings for surface modification of the biodegradable magnesium alloy implants. The design idea of the new type of biomaterial is belong to the concept of "third generation biomaterial". Corrosion behavior and bioactivity of coated magnesium alloy are the key issues during implantation. In this study, preparation and corrosion behavior of magnesium phytic acid/hydroxyapatite composite coatings on magnesium alloy were studied. The basic findings and significance of this paper are as follows: 1. A novel environmentally friendly, homogenous and crack-free magnesium phytic acid/hydroxyapatite composite coating was fabricated on AZ31 magnesium alloy via chemical conversion deposition technology with the aim of enhancing its corrosion resistance and bioactivity. The chemical conversion coatings, which are formed through the reaction between the substrate and the environment, have attracted increasing attention owing to the relative low treatment temperature, favorable bonding to substrate and simple implementation process. 2. With the increasing of hydroxyapatite (HA) content, the crack width in the composite coatings and the thickness of the coatings exhibit obviously decreased. The reason is probably that when adding HA into the phytic acid solution, the amount of active hydroxyl groups in the phytic acid are reduced via forming the coordination bond between P-OH groups from phytic acid and P-OH groups from the surface of HA, thus decreasing the coating thickness and hydrogen formation, as well as avoiding coating cracking. 3. By adjusting the HA content to 45 wt.%, a dense and relatively smooth composite coating with ~1.4 µm thickness is obtained on magnesium alloy, and exhibits high corrosion resistance and good bioactivity when compared with the single phytic acid conversion coating.

Design of public open space: Site features, playing, and physical activity.

Not enough studies have examined how specific design features of public open space, such as movable site features, are associated with people's physical activity level or playfulness. To fill this gap, this study uses deep learning-based methods to extract visitors' movement trajectories (n = 18,592) from a time-lapse video of a promenade in Hong Kong. The trajectories are classified into different groups based on a set of movement indicators. Multinomial logistic regression is used to examine the relationship between trajectory types and the level of interaction with different site features. A one-way analysis of variance (ANOVA) is also used to compare the average amount of physical activity among different trajectory types. The results show that interaction with semi-fixed or movable site features is associated with higher odds of people having "playful" trajectories than other types of trajectories. People with "sporty" trajectories and "playful" trajectories on average have the highest amount of physical activity.

TPI1 promotes MAPK/ERK-induced EMT, cell migration and invasion in lung adenocarcinoma.

BACKGROUND: Triosephosphate isomerase 1 (TPI1), as a widely involved glycolytic enzyme, plays a significant role in glucose metabolism and is highly expressed in various tumors. However, its role in lung adenocarcinoma (LUAD) remains incompletely understood. METHODS: Through bioinformatic analysis, we identified a positive association between high expression of TPI1 and metastasis in LUAD. Western blot, RT-qPCR, wound healing assays and transwell experiments, were employed to investigate potential mechanisms. RESULTS: In this study, bioinformatic analysis showed that high expression of TPI1 was associated with poor prognosis in LUAD patients. We examined the expression of TPI1 in 29 paired LUAD tissues and found that TPI1 expression was higher in LUAD tissues than in paired adjacent noncancerous tissues. Meanwhile, overexpression of TPI1 promoted the epithelial-mesenchymal transition (EMT) process in LUAD cells, while silencing TPI1 weakened the EMT process. Furthermore, TPI1 was shown to regulate EMT through the MAPK/ERK signaling pathway. CONCLUSION: TPI1 promotes LUAD metastasis by activating the MAPK/ERK signaling pathway.

Multi-omics analysis of the prognostic and biological role of cuproptosis-related gene in gastric cancer.

Background: A considerable number of gastric cancer (GC) patients cannot receive benefits from current treatments. We aimed to identify possible biomarkers of cuproptosis-related genes (CRGs) in GC patients, which may help guide precision medicine-based decision-making. Methods: RNA sequencing data, copy number variations (CNVs) data, and single nucleotide variant (SNV) data were obtained from The Cancer Genome Atlas (TCGA) database and Gene Set Cancer Analysis (GSCA) database. Chi-squared test was adopted to screen differentially expressed CRGs (DE-CRGs) between samples from 14 kinds of carcinoma and adjacent tissue samples. Then, GC samples were divided into high- and low-expressed groups based on DE-CRGs for further survival analyses and the selection of biomarkers. Methylation sites related with biomarkers were acquired. The correlation between immune cells and biomarkers was verified. Finally, miRNA-mRNA, TFs-mRNA, and co-expression networks were established to detect factors with regulating effects on biomarkers. Results: Three CRGs including LIAS, GLS, and CDKN2A were identified as biomarkers in GC patients. Three methylation sites with a significant survival effect including cg13601799, 07562918, and 07253264 were acquired. Then, we found that B cells native was significantly correlated with CDKN2A, four immune cells such as T cells regulatory are significantly correlated with GLS, and two immune cells such as T cells CD4 memory activated were significantly correlated with LIAS. Moreover, 10 miRNAs in the miRNA-mRNA network and three transcription factors (TFs) in the TFs-mRNA network had a significant correlation with overall survival (OS). Finally, 20 enrichment functions were obtained on the basis of the co-expression network. Conclusions: Three biomarkers with a prognosis prediction value of GC were found, and multi-factor regulatory networks were constructed to screen out 13 factors with regulating influences of biomarkers.

Anti-Helicobacter pylori Treatment in Patients With Gastric Cancer After Radical Gastrectomy.

Importance: Whether anti-Helicobacter pylori treatment can provide survival benefits for patients with gastric cancer who are diagnosed with H pylori infection is an area with limited research. Objective: To explore the potential survival benefits of anti-H pylori treatment after radical gastrectomy in patients with gastric cancer and presurgical confirmation of H pylori infection. Design, Setting, and Participants: This retrospective cohort study was conducted using data from patients with gastric cancer treated between January 1, 2010, and December 31, 2018, and followed up for outcome ascertainment until May 19, 2021. Propensity score matching was performed in patients treated with or without anti-H pylori treatment. This study involved a single institute in a comprehensive cancer treatment and research center located in Guangzhou, Guangdong Province, China. The study included patients with gastric or esophagogastric junction adenocarcinoma who underwent curative gastrectomy with D2 lymphadenectomy and tested positive for H pylori infection. Data were analyzed from March to June 2023. Exposure: Anti-H pylori treatment, which primarily includes triple therapy regimens consisting of amoxicillin, clarithromycin, and omeprazole for 14 days. Main Outcomes and Measures: Clinical outcomes, including overall survival (OS) and disease-free survival (DFS), were analyzed by Kaplan-Meier method, log-rank test, and Cox proportional hazards regression model. Subgroup analysis based on crucial clinical information was also conducted. Results: All 1293 patients (median [IQR] age, 59 [50-65] years; 860 [66.5%] male) were divided into 2 groups, with 125 patients in the anti-H pylori treatment group and 1168 patients in the non-anti-H pylori treatment group based on whether they received anti-H pylori treatment during the perioperative period and the follow-up. Survival analysis showed that the 5-year OS rates were 94.1% (95% CI, 89.3%-99.2%) in the anti-H pylori group and 73.8% (95% CI, 70.7%-77.0%) in the non-anti-H pylori group, and the hazard ratio (HR) of these 2 groups was 0.33 (95% CI, 0.18-0.60; P < .001). The survival benefit remained after propensity score matching (HR, 0.50; 95% CI, 0.26-0.99; P = .048). Multivariable analysis for OS and DFS further showed the survival benefit of anti-H pylori treatment, with HRs of 0.38 (95% CI, 0.17-0.87; P = .02) and 0.48 (95% CI, 0.28-0.83; P = .008), respectively. Among patients with TNM stage II/III disease who received adjuvant chemotherapy, anti-H pylori treatment was associated with survival benefits (OS: HR, 0.49; 95% CI, 0.24-0.99; P = .046), whereas among those who did not receive adjuvant chemotherapy, anti-H pylori treatment was not associated with survival benefits (OS: HR, 0.29; 95% CI, 0.04-2.08; P = .22). Conclusions and Relevance: This cohort study indicates that anti-H pylori treatment may be associated with improved survival in patients with gastric cancer who have H pylori infections. The study reinforces the importance of including H pylori screening and treatment in the surgical treatment of these patients.

Bacteriophage-resistant carbapenem-resistant Klebsiella pneumoniae shows reduced antibiotic resistance and virulence.

Phage therapy has shown great promise in the treatment of bacterial infections. However, the effectiveness of phage therapy is compromised by the inevitable emergence of phage-resistant strains. In this study, a phage-resistant carbapenem-resistant Klebsiella pneumoniae strain SWKP1711R, derived from parental carbapenem-resistant K. pneumoniae strain SWKP1711 was identified. The mechanism of bacteriophage resistance in SWKP1711R was investigated and the molecular determinants causing altered growth characteristics, antibiotic resistance, and virulence of SWKP1711R were tested. Compared to SWKP1711, SWKP1711R showed slower growth, smaller colonies, filamentous cells visible under the microscope, reduced production of capsular polysaccharide (CPS) and lipopolysaccharide, and reduced resistance to various antibiotics accompanied by reduced virulence. Adsorption experiments showed that phage vB_kpnM_17-11 lost the ability to adsorb onto SWKP1711R, and the adsorption receptor was identified to be bacterial surface polysaccharides. Genetic variation analysis revealed that, compared to the parental strain, SWKP1711R had only one thymine deletion at position 78 of the open reading frame of the lpcA gene, resulting in a frameshift mutation that caused alteration of the bacterial surface polysaccharide and inhibition of phage adsorption, ultimately leading to phage resistance. Transcriptome analysis and quantitative reverse transcriptase PCR revealed that genes encoding lipopolysaccharide synthesis, ompK35, blaTEM-1, and type II and Hha-TomB toxin-antitoxin systems, were all downregulated in SWKP1711R. Taken together, the evidence presented here indicates that the phenotypic alterations and phage resistance displayed by the mutant may be related to the frameshift mutation of lpcA and altered gene expression. While evolution of phage resistance remains an issue, our study suggests that the reduced antibiotic resistance and virulence of phage-resistant strain derivatives might be beneficial in alleviating the burden caused by multidrug-resistant bacteria.

Co-occurrence of ST412 Klebsiella pneumoniae isolates with hypermucoviscous and non-mucoviscous phenotypes in a short-term hospitalized patient.

Hypermucoviscosity (HMV) is a phenotype that is commonly associated with hypervirulence in Klebsiella pneumoniae. The factors that contribute to the emergence of HMV subpopulations remain unclear. In this study, eight K. pneumoniae strains were recovered from an inpatient who had been hospitalized for 20 days. Three of the isolates exhibited a non-HMV phenotype, which was concomitant with higher biofilm formation than the other five HMV isolates. All eight isolates were highly susceptible to serum killing, albeit HMV strains were remarkably more infective than non-HMV counterparts in a mouse model of infection. Whole genome sequencing (WGS) showed that the eight isolates belonged to the K57-ST412 lineage. Average nucleotide identity (FastANIb) analysis indicated that eight isolates share 99.96% to 99.99% similarity and were confirmed to be the same clone. Through comparative genomics analysis, 12 non-synonymous mutations were found among these isolates, eight of which in the non-HMV variants, including rmpA (c.285delG) and wbaP (c.1305T > A), which are assumed to be associated with the non-HMV phenotype. Mutations in manB (c.1318G > A), dmsB (c.577C > T) and tkt (c.1928C > A) occurred in HMV isolates only. RNA-Seq revealed transcripts of genes involved in energy metabolism, carbohydrate metabolism and membrane transport, including cysP, cydA, narK, tktA, pduQ, aceB, metN, and lsrA, to be significantly dysregulated in the non-HMV strains, suggesting a contribution to HMV phenotype development. This study suggests that co-occurrence of HMV and non-HMV phenotypes in the same clonal population may be mediated by mutational mechanisms as well as by certain genes involved in membrane transport and central metabolism. IMPORTANCE: K. pneumoniae with a hypermucoviscosity (HMV) phenotype is a community-acquired pathogen that is associated with increased invasiveness and pathogenicity, and underlying diseases are the most common comorbid risk factors inducing metastatic complications. HMV was earlier attributed to the overproduction of capsular polysaccharide, and more data point to the possibility of several causes contributing to this bacterial phenotype. Here, we describe a unique event in which the same clonal population showed both HMV and non-HMV characteristics. Studies have demonstrated that this process is influenced by mutational processes and genes related to transport and central metabolism. These findings provide fresh insight into the mechanisms behind co-occurrence of HMV and non-HMV phenotypes in monoclonal populations as well as potentially being critical in developing strategies to control the further spread of HMV K. pneumoniae.