Trophic transfer of antibiotics in the benthic-pelagic coupling foodweb in a macrophyte-dominated shallow lake: The importance of pelagic-benthic coupling strength and baseline organism.

In lake ecosystems, pelagic-benthic coupling strength (PBCS) is closely related to foodweb structure and pollutant transport. However, the trophic transfer of antibiotics in a benthic-pelagic coupling foodweb (BPCFW) and the manner in which PBCS influences the trophic magnification factor (TMFs) of antibiotics is still not well understood in the whole lake. Herein, the trophic transfer behavior of 12 quinolone antibiotics (QNs) in the BPCFW of Baiyangdian Lake were studied during the period of 2018-2019. It was revealed that 24 dominant species were contained in the BPCFW, and the trophic level was 0.42-2.94. Seven QNs were detected in organisms, the detection frequencies of ofloxacin (OFL), flumequine (FLU), norfloxacin (NOR), and enrofloxacin (ENR) were higher than other QNs. The ∑QN concentration in all species was 11.3-321 ng/g dw. The TMFs for ENR and NOR were trophic magnification, while for FLU/OFL it was trophic dilution. The PBCS showed spatial-temporal variation, with a range of 0.6977-0.7910. The TMFs of ENR, FLU, and OFL were significantly positively correlated with PBCS. Phytoplankton and macrophyte biomasses showed indirect impact on the TMFs of QNs by directly influencing the PBCS. Therefore, the PBCS was the direct influencing factor for the TMFs of chemicals.

Characterization and Antioxidant and Antibacterial Activities of Carboxymethylated Tamarind Seed Polysaccharide Composite Films Incorporated with ε-Polylysine and Their Application in Fresh-Cut Green Bell Pepper Preservation.

Traditional petroleum-based food-packaging materials have poor permeability, limited active packaging properties, and difficulty in biodegradation, limiting their application. We developed a carboxymethylated tamarind seed polysaccharide composite film incorporated with ε-polylysine (CTPε) for better application in fresh-cut agricultural products. The CTPε films exhibit excellent water vapor barrier properties, but the mechanical properties are slightly reduced. Fourier transform infrared spectroscopy and X-ray diffraction spectra indicate the formation of hydrogen bonds between ε-PL and CTP, leading to their internal reorganization and dense network structure. With the increase of ε-PL concentration, composite films showed notable inhibition of postharvest pathogenic fungi and bacteria, a significant enhancement of 2,2'- azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical-scavenging activity, and gradual improvement of wettability performance. Cytotoxicity experiments confirmed the favorable biocompatibility when ε-PL was added at 0.3% (CTPε2). In fresh-cut bell pepper preservation experiments, the CTPε2 coating effectively delayed weight loss and malondialdehyde increase preserved the hardness, color, and nutrients of fresh-cut peppers and prolonged the shelf life of the fresh-cut peppers, as compared with the control group. Therefore, CTPε composite films are expected to be a valuable packaging material for extending the shelf life of freshly cut agricultural products.

Development and Characterization of Modified Gelatin-Based Cling Films with Antimicrobial and Antioxidant Activities and Their Application in the Preservation of Cherry Tomatoes.

The utilization of functional cling films presents a promising approach to alleviate post-harvest spoilage caused by microbial activity, oxidative metabolism, and moisture loss in agricultural products. To overcome the environmental problems of conventional packaging materials, in this study, we developed functional fruit and vegetable cling films based on glycidyltrimethylammonium chloride and rosemarinic acid cross-linked gelatin (RQ-GEL). The results indicate that the prepared RQ-GEL film possesses excellent UV light barrier properties and mechanical performance. RQ-GEL inhibited S. aureus and E. coli by 93.79% and 92.04%, respectively. DPPH and ABTS free radical scavenging activities were as high as 87.69% and 84.6%. In the cherry tomato preservation experiment, when compared to uncovered samples, the RQ-GEL group had a 29.77% reduction in weight loss and a significant 26.92% reduction in hardness. Meanwhile, the RQ-GEL group delays the decline of fruit total soluble solids and titratable acidity content, and prolongs the preservation period of cherry tomatoes. Hence, RQ-GEL cling film is poised to emerge as a promising packaging material for the post-harvest preservation of agricultural products.

Antifungal Activities of L-Methionine and L-Arginine Treatment In Vitro and In Vivo against Botrytis cinerea.

Gray mold caused by Botrytis cinerea is a common postharvest fungal disease in fruit and vegetables. The prevention and treatment of postharvest gray mold has been one of the hot research issues addressed by researchers. This study aimed to investigate the effect of L-methionine and L-arginine on Botrytis cinerea in vitro and on cherry tomato fruit. The results of the in vitro experiment showed that L-methionine and L-arginine had significant inhibitory effects on the mycelial growth and spore germination of Botrytis cinerea, and the inhibitory effects were enhanced with increasing L-methionine or L-arginine concentration. In addition, L-methionine and L-arginine treatment increased the leakage of Botrytis cinerea electrolytes, proteins and nucleic acids. The experiment involving propidium iodide staining and malondialdehyde content assay also confirmed that L-methionine and L-arginine treatment could lead to cell membrane rupture and lipid peroxidation. The results of scanning electron microscopy further verified that the morphology of hyphae was damaged, deformed, dented and wrinkled after treatment with L-methionine or L-arginine. Fruit inoculation experiments displayed that L-methionine and L-arginine treatments significantly inhibited the occurrence and development of gray mold in postharvest cherry tomato. Therefore, treatment with L-methionine or L-arginine might be an effective means to control postharvest gray mold in fruit and vegetables.

Lysophosphatidic acid responsive photosensitive supramolecular organic frameworks for tumor imaging, drug loading, and photodynamic therapy.

Supramolecular organic frameworks have been widely applied for biological detection and drug delivery. In this study, a supramolecular organic framework (SOF) is constructed through the self-assembly of a highly photosensitive triarylphosphine oxide guest molecule, OTPP-6-Methyl, with cucurbit [8] uril (CB [8]). The formation of the SOF gradually enhances the weak fluorescence of OTPP-6-Methyl owing to the restriction of the molecular folding motion. Although the high positive charge of OTPP-6-Methyl facilitates binding to various negatively charged substances, the SOF system only demonstrated an obvious fluorescence response to LPA, a biomarker of ovarian cancer, via the disassembly of SOF and subsequent binding of OTPP-6-Methyl with LPA. The fluorescence changes during the entire process are insufficient to allow the sensitive detection of LPA; thus, we further designed a FRET system by introducing Cy5, which can act as an energy receptor to achieve a ratiometric readout for LPA. The tumor-targeting cRGD group was introduced into the SOF system as part of another guest molecule, OTPP-5-M-1-cRGD, to improve the tumor-targeting ability of the SOF system. The SOF system further improves the photosensitivity of guest molecules, and is therefore used in the in vivo imaging of ovarian cancer subcutaneous tumors and as a DDS for loading DOX for the combined in vivo chemotherapy and photodynamic treatment of tumors.

Co-Occurrence of tet(X4) and blaNDM-5 in Escherichia coli Isolates of Inpatient Origin in Guangzhou, China.

Tigecycline, one of the last-resort therapeutic options for complicated infections caused by multidrug-resistant pathogens, especially carbapenem-resistant Enterobacterales and Acinetobacter in recent years. The emergence of antibiotic-resistant bacteria and antibiotic-resistant genes has threatened the effectiveness of antibiotics and public health with the excessive use of antibiotics in clinics. However, the emergence and dissemination of high-level mobile tigecycline-resistance gene tet(X) is challenging for clinical effectiveness of antimicrobial agent. This study aimed to characterize an E. coli strain T43, isolated from an inpatient in a teaching hospital in China. The E. coli T43 was resistant to almost all antimicrobials except colistin and consisted of a 4,774,080 bp chromosome and three plasmids. Plasmids pT43-1 and pT43-2 contained tigecycline-resistance gene tet(X4). Plasmid pT43-1 had a size of 152,423 bp with 51.05% GC content and harbored 151 putative open reading frames. pT43-1 was the largest plasmid in strain T43 and carried numerous resistance genes, especially tigecycline resistance gene tet(X4) and carbapenemase resistance gene blaNDM-5. The tet(X) gene was associated with IS26. Co-occurrence of numerous resistance genes in a single plasmid possibly contributed to the dissemination of these genes under antibiotics stress. It might explain the presence of clinically crucial resistance genes tet(X) and blaNDM-5 in clinics. This study suggested the applicable use of antibiotics and continued surveillance of tet(X) and blaNDM-5 in clinics are imperative.

Discriminative fusion of moments-aligned latent representation of multimodality medical data.

Fusion of multimodal medical data provides multifaceted, disease-relevant information for diagnosis or prognosis prediction modeling. Traditional fusion strategies such as feature concatenation often fail to learn hidden complementary and discriminative manifestations from high-dimensional multimodal data. To this end, we proposed a methodology for the integration of multimodality medical data by matching their moments in a latent space, where the hidden, shared information of multimodal data is gradually learned by optimization with multiple feature collinearity and correlation constrains. We first obtained the multimodal hidden representations by learning mappings between the original domain and shared latent space. Within this shared space, we utilized several relational regularizations, including data attribute preservation, feature collinearity and feature-task correlation, to encourage learning of the underlying associations inherent in multimodal data. The fused multimodal latent features were finally fed to a logistic regression classifier for diagnostic prediction. Extensive evaluations on three independent clinical datasets have demonstrated the effectiveness of the proposed method in fusing multimodal data for medical prediction modeling.

Resistome and Genome Analysis of an Extensively Drug-Resistant Klebsiella michiganensis KMIB106: Characterization of a Novel KPC Plasmid pB106-1 and a Novel Cointegrate Plasmid pB106-IMP Harboring blaIMP-4 and blaSHV-12.

Klebsiella michiganensis is a recently emerging human pathogen causing nosocomial infections. This study aimed to characterize the complete genome sequence of a clinical Klebsiella michiganensis strain KMIB106 which exhibited extensive drug-resistance. The whole genome of the strain was sequenced using PacBio RS III systems and Illumina Nextseq 500. Annotation, transposable elements and resistance gene identification were analyzed by RAST, prokka and Plasmid Finder, respectively. According to the results, KMIB106 was resistant to multiple antimicrobials, including carbapenems, but it remained susceptible to aztreonam. The genome of KMIB106 consisted of a single chromosome and three predicted plasmids. Importantly, a novel KPC plasmid pB106-1 was found to carry the array of resistance genes in a highly different order in its variable regions, including mphA, msrE, mphE, ARR-3, addA16, sul1, dfrA27, tetD and fosA3. Plasmid pB106-2 is a typical IncFII plasmid with no resistant gene. Plasmid pB106-IMP consists of the IncN and IncX3 backbones, and two resistance genes, blaIMP-4 and blaSHV-12, were identified. Our study for the first time reported an extensively drug-resistant Klebsiella michiganensis strain recovered from a child with a respiratory infection in Southern China, which carries three mega plasmids, with pB106-1 firstly identified to carry an array of resistance genes in a distinctive order, and pB106-IMP identified as a novel IncN-IncX3 cointegrate plasmid harboring two resistance genes blaIMP-4 and blaSHV-12.

[Source Analysis and Health Risk Assessment of Heavy Metals in the Groundwater of Shijiazhuang, a Typical City in North China Plain].

Increasing attention has been paid to the heavy metal pollution in groundwater. The source analysis and risk assessment of heavy metals will provide data and method support for the targeted control of heavy metal pollution in groundwater. In this study, 20 sampling sites were selected in Shijiazhuang City. The APCS-MLR model and health risk model were applied to analyze and evaluate the pollution sources and health risks of 10 types of heavy metals in the groundwater of Shijiazhuang. The results showed that ① the mean concentration of heavy metals in groundwater followed the order of Fe>Zn>Mn>Cu>Al>Pb>Cr>As>Cd>Hg, and the mean ρ(Fe) and ρ(Pb) were 260.3 µg·L-1 and 10.01 µg·L-1, respectively. According to the results of the single factor and Nemerow index, Pb, Fe, and Cd primarily contributed to the heavy metal pollution in the groundwater. ② The concentration of heavy metals ranged from 47.30 to 2560 µg·L-1. In terms of spatial distribution, the highest concentration appeared at S3 (2560 µg·L-1), whereas the lowest concentration was at S9 (47.30 µg·L-1). ③ Source analysis results showed that industrial and agricultural activities, transportation emission, and geological background were the major heavy metal sources, among which the contribution of industrial and agricultural activities was the highest (47.83%). ④ The industrial-agricultural activities posed a potential threat to adults (HI>1); however, the non-cancer and the cancer risks of other sources for both adults and children were at an acceptable level (HI<1) and potential threat level, respectively; industrial-agricultural activities were the major source of non-cancer (adults:52.46%, children:52.45%) and cancer risks (adults:65.22%, children:65.69%), among which Cd and As showed high cancer risk. Therefore, to ensure the safety of the groundwater environment, strictly controlling the pollution sources and further strengthening the risk control of heavy metal pollution in groundwater are necessary.

[Source Apportionment and Source-specific Risk of Typical Antibiotics in Baiyangdian Lake].

The current situation of antibiotic pollution in lakes is critical. At present, most of the previous studies on antibiotics in lakes have focused on the spatiotemporal distribution and risk assessment, while less attention has been paid to the source apportionment. Ultra-high performance liquid chromatography-mass spectrometry was used to determine the concentration of tetracyclines (TCs), sulfonamides (SAs), and quinolones (QNs) in the samples. The source apportionment and source-specific risk of typical antibiotics in the study area were analyzed using the combination of a PMF model and risk quotients (RQ). The results showed that ① the total concentrations of target antibiotics (Σ antibiotics) ranged from ND to 2635 ng·L-1 for surface water and from ND to 259.8 ng·g-1 for sediments. ② The spatial distribution of QNs in surface water decreased from west to east, SAs decreased from middle to north and south, and TCs increased from middle to north and south. In the sediment, QNs decreased from middle to east and west, whereas SAs and TCs increased from east to west. ③ Aquaculture was the major antibiotic source, accounting for the highest proportion (33.2%), followed by sewage treatment plants (29.2%), livestock activities (18.9%), and domestic sewage (18.7%). ④ The ecological risk assessment results showed that enrofloxacin and flumequine were at a medium-high risk level. ⑤ For the spatial distribution of source-specific risk, the results showed that the aquaculture at S1 was at a high risk level, whereas the source-specific risks for other sites were at a medium-low risk level. In terms of source types, aquaculture was at a medium-high risk level, whereas the other sources were at a medium-low risk level. Therefore, considering the major sources and source-specific risk level of antibiotics, more precise and scientific antibiotic risk control should be adopted in Baiyangdian Lake.

Immediate effects of electroacupuncture in oculomotor nerve palsy following brainstem infarction: A case report.

INTRODUCTION: Research has demonstrated that electroacupuncture (EA) stimulation of paralyzed muscles significantly improves nerve regeneration and functional recovery. DESCRIPTION: An 81-year-old man with no history of diabetes mellitus or hypertension presented with a history of brainstem infarction. Initially, the patient had medial rectus palsy in the left eye and diplopia to the right in both eyes, which almost returned to normal after six sessions of EA. METHODS: The CARE guidelines informed the case study report. The patient was diagnosed with oculomotor nerve palsy (ONP) and photographed to document ONP recovery after treatment. The selected acupuncture points and surgical methods are listed in the table. DISCUSSION: Pharmacological treatment of oculomotor palsy is not ideal, and its long-term use has side effects. Although acupuncture is a promising treatment for ONP, existing treatments involve many acupuncture points and long cycles, resulting in poor patient compliance. We chose an innovative modality, electrical stimulation of paralyzed muscles, which may be an effective and safe complementary alternative therapy for ONP.

Machine Learning-Based Multiomics Prediction Model for Radiation Pneumonitis.

Objective: The study aims to establish and validate an effective CT-based radiation pneumonitis (RP) prediction model using the multiomics method of radiomics and EQD2-based dosiomics. Materials and Methods: The study performed a retrospective analysis on 91 nonsmall cell lung cancer patients who received radiotherapy from 2019 to 2021 in our hospital. The patients with RP grade ≥1 were labeled as 1, and those with RP grade < 1 were labeled as 0. The whole lung excluding clinical target volume (lung-CTV) was used as the region of interest (ROI). The radiomic and dosiomic features were extracted from the lung-CTV area's image and dose distribution. Besides, the equivalent dose of the 2 Gy fractionated radiation (EQD2) model was used to convert the physical dose to the isoeffect dose, and then, the EQD2-based dosiomic (eqd-dosiomic) features were extracted from the isoeffect dose distribution. Four machine learning (ML) models, including DVH, radiomics combined with DVH (radio + DVH), radiomics combined with dosiomics (radio + dose), and radiomics combined with eqd-dosiomics (radio + eqdose), were established to construct the prediction model via eleven different classifiers. The fivefold cross-validation was used to complete the classification experiment. The area under the curve (AUC) of the receiver operating characteristics (ROC), accuracy, precision, recall, and F1-score were calculated to assess the performance level of the prediction models. Results: Compared with the DVH, radio + DVH, and radio + dose model, the value of the training AUC, accuracy, and F1-score of radio + eqdose was higher, and the difference was statistically significant (p < 0.05). Besides, the average value of the precision and recall of radio + eqdose was higher, but the difference was not statistically significant (p > 0.05). Conclusion: The performance of using the ML-based multiomics method of radiomics and eqd-dosiomics to predict RP is more efficient and effective.

Machine learning based multi-label classification of single or mixed-composition urinary stones in in vivo spectral CT.

BACKGROUND: Urinary stones comprise both single and mixed compositions. Knowledge of the stone composition helps the urologists choose appropriate medical interventions for patients. The parameters from the spectral computerized tomography (CT) analysis have potential values for identification of the urinary stone compositions. PURPOSE: The present study aims to identify the compositions of urinary stones in vivo using parameters from spectral CT and machine learning, based on multi-label classification modeling. METHODS: This retrospective study collected 252 urinary stone samples with single/mixed compositions (including carbapatite [CP], calcium oxalate monohydrate [COM], calcium oxalate dehydrate [COD], uric acid [UA], and struvite [STR]), which were confirmed by ex vivo infrared spectroscopy. Parameters were extracted from an energy spectrum analysis (ESA) of the spectral CT, including the effective atomic number (Zeff ), Zeff histogram, CT values at a given x-ray energy level, and material densities. These ESA parameters were utilized for composition analysis via a multi-label classification fusion framework, where 250 multi-label models were built and the classification decisions from the top performance models were integrated by a multi-criterion weighted fusion (MCWF) approach in order to reach a consensus prediction. An example-based metric A c c e x a m $Ac{c_{exam}}$ and label-based metric A c c l a b e l $Ac{c_{label}}$ were used for global and label-wise accuracy evaluations, respectively. The top-ranked parameters associated with discriminating the stone composition were also identified. RESULTS: The multi-label classification fusion framework achieved an overall A c c e x a m $Ac{c_{exam}}$ of 81.2%, with A c c l a b e l $Ac{c_{label}}$ of 86.7% (CP), 90.6% (COM), 80.6% (COD), 95.0% (UA), and 94.4% (STR) for each composition on the independent testing cohort 1, and A c c e x a m $Ac{c_{exam}}$ of 76.4% with A c c l a b e l $Ac{c_{label}}$ of 80.5% (CP), 88.7% (COM), 74.9% (COD), 94.4% (UA), and 98.5% (STR) on the independent testing cohort 2. CONCLUSION: The parameters extracted from the ESA on spectral CT can be utilized to characterize single or mixed stone compositions via multi-label classification modeling. The generalization capability of the proposed methodology still requires further verification.

Proteomics profiling of ertapenem challenged major porin deficient carbapenem-resistant Klebsiella pneumoniae.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an urgent threat to human health. Major outer membrane proteins (OMPs) porin mutation is one important resistance mechanism of CRKP, and may also affect the inhibition activity of ß-lactam and ß-lactamase inhibitor combinations. The ertapenem-resistant K. pneumoniae strain 2018B120 with major porin mutations was isolated from a clinical patient. Genomic and time-series proteomic analyses were conducted to retrieve the ertapenem-challenged response of 2018B120. The abundance changing of proteins from PTS systems,  ABC transporters, the autoinducer 2 (AI-2) quorum sensing system, and antioxidant systems can be observed. Overexpression of alternative porins was also noticed to balance major porins' defection. These findings added a detailed regulation network in bacterial resistance mechanisms and gave new insights into bypass adaptation mechanisms the porin deficient bacteria adopted under carbapenem antibiotics pressure. SIGNIFICANCE: Outer membrane porins deficiency is an important mechanism of carbapenem resistance in K. pneumoniae. Comprehensive genomic and proteomic profiling of an ertapenem-resistant K. pneumoniae strain 2018B120 gives a detailed systematic regulation network in bacterial resistance mechanisms. Overexpression of alternative porins to balance major porins' defection was noticed, giving new insights into bypass adaptation mechanisms of porin deficient bacteria.

Efficacy of Traditional Chinese Exercise in Improving Gait and Balance in Cases of Parkinson's Disease: A Systematic Review and Meta-analysis.

Background: The efficacy of traditional Chinese exercise (TCE)-based intervention in the improvement of motor function in patients with Parkinson's disease (PD) is controversial. The present study aimed to assess the effects of TCE on balance and gait outcomes, as well as motor symptoms in individuals with PD, and evaluate potential discrete moderators such as TCE dosage-related variables. Method: PubMed, Embase, Cochrane's Library, Web of Science, Medline, and Scopus were systematically searched from their dates of inception to February 2022. All studies were randomized controlled trials (RCTs) of TCE-based interventions for PD. The treatment effects were estimated using a random-effect meta-analysis model with standardized mean differences (Hedges' g). The Physiotherapy Evidence Database was used to evaluate the methodological quality of the study. Result: Fifteen studies involving a total of 873 participants were included in the final analysis. The meta-analytic findings revealed significant improvements in balance outcomes [Berg Balance Scales (BBS) (g = 0.83, 95% CI = 0.37-1.29, p = 0.000, I2 = 84%), time up and go (TUG) (g = -0.80, 95% CI = -1.13- -0.47, p = 0.000, I2 = 81%), and the one legged blind balance test (g = 0.49, 95% CI = 0.13-0.86, p = 0.01, I2 = 10%)], as well as gait outcomes [gait velocity (g = 0.28, 95% CI = 0.02-0.54, p = 0.04, I2 = 64%), 6-min walking test (6MWT) (g = 0.32, 95% CI 0.01-0.62, p = 0.04, I 2= 15%), stride length (g = 0.25, 95% CI = 0.08-0.41, p = 0.003, I2 = 42%)], and motor symptoms [Unified Parkinson's Disease Rating Scale part III (UPDRS-III) (g = -0.77, 95% CI = -1.06- -0.48, p = 0.000, I2 = 76%)]. However, cadence (g = -0.03) and step length (g = 0.02) did not differ significantly. The moderator shows that the effects of TCE on BBS and gait velocity were moderated by Pedro score, exercise type, control group type, and number of sessions. Meta-regression found that TCE (exercise duration, number of sessions, and session duration) was significantly associated with improved UPDRS-III and BBS scores. Conclusion: These findings provide evidence for the therapeutic benefits of TCE as an adjunct therapy for patients with PD. TEC dosage (high-intensity long sessions) may moderate some favorable effects. Systematic Review Registration: PROSPERO, identifier CRD42022314686.

Characterizing the Effect of the Lysine Deacetylation Modification on Enzyme Activity of Pyruvate Kinase I and Pathogenicity of Vibrio alginolyticus.

Pyruvate kinase I (PykF) is one of the key enzymes of glycolysis and plays a crucial role in bacterial metabolism. Several acetylation sites of Vibrio alginolyticus PykF were reported in previous studies and then 11 sites were first verified in this study, however, the specific roles of PykF acetylation remains unclear. Overlap-PCR and homologous recombination were implied to delete V. alginolyticus pykF gene and constructed complementary strains of site-directed mutagenesis for the further research focus on the deacetylation regulation on PykF. The results showed that the pyruvate kinase activity was sharply suppressed in the deacetylation status of K52, K68, and K317 of PykF, as well as the extracellular protease activity was significantly decreased in the deacetylation status of K52 and K68, but not induced with K317. Moreover, the growth rates of V. alginolyticus were not influenced with these three deacetylation sites. The ΔpykF mutant exhibited a 6-fold reduction in virulence to zebrafish. Site-directed mutations of K52R and K68R also showed reduced virulence while mutations of K317R didn't. The in vitro experiments showed that PykF was acetylated by acetyl phosphate (AcP), with the increase of incubation time by AcP, the acetylation level of PykF increased while the enzyme activity of PykF decreased correspondingly. Besides, PykF was deacetylated by CobB deacetylase and in result that the deacetylation was significantly down-regulated while the pyruvate kinase activity of PykF increased. Moreover, deletion of cobB gene had no significant difference in pyruvate kinase activity. These results confirm that CobB can regulate the acetylation level and pyruvate kinase activity of PykF. In summary, the results of this study provide a theoretical basis for further understanding of the deacetylation modification of PykF. It provides a new idea for the prevention and cure of vibriosis.

Helicobacter pylori-Induced Progranulin Promotes the Progression of the Gastric Epithelial Cell Cycle by Regulating CDK4.

Helicobacter pylori, a group 1 carcinogen, colonizes the stomach and affects the development of stomach diseases. Progranulin (PGRN) is an autocrine growth factor that regulates multiple cellular processes and plays a tumorigenic role in many tissues. Nevertheless, the mechanism of action of PGRN in gastric cancer caused by H. pylori infection remains unclear. Here, we investigated the role of PGRN in cell cycle progression and the cell proliferation induced by H. pylori infection. We found that the increased PGRN was positively associated with CDK4 expression in gastric cancer tissue. PGRN was upregulated by H. pylori infection, thereby promoting cell proliferation, and that enhanced level of proliferation was reduced by PGRN inhibitor. CDK4, a target gene of PGRN, is a cyclin-dependent kinase that binds to cyclin D to promote cell cycle progression, which was upregulated by H. pylori infection. We also showed that knockdown of CDK4 reduced the higher cell cycle progression caused by upregulated PGRN. Moreover, when the PI3K/Akt signaling pathway (which is promoted by PGRN) was blocked, the upregulation of CDK4 mediated by PGRN was reduced. These results reveal the potential mechanism by which PGRN plays a major role through CDK4 in the pathological mechanism of H. pylori infection.

Pan-Genome Analysis of Laribacter hongkongensis: Virulence Gene Profiles, Carbohydrate-Active Enzyme Prediction, and Antimicrobial Resistance Characterization.

Laribacter hongkongensis is a new emerging foodborne pathogen that causes community-acquired gastroenteritis and traveler's diarrhea. However, the genetic features of L. hongkongensis have not yet been properly understood. A total of 45 aquatic animal-associated L. hongkongensis strains isolated from intestinal specimens of frogs and grass carps were subjected to whole-genome sequencing (WGS), along with the genome data of 4 reported human clinical strains, the analysis of virulence genes, carbohydrate-active enzymes, and antimicrobial resistance (AMR) determinants were carried out for comprehensively understanding of this new foodborne pathogen. Human clinical strains were genetically more related to some strains from frogs inferred from phylogenetic trees. The distribution of virulence genes and carbohydrate-active enzymes exhibited different patterns among strains of different sources, reflecting their adaption to different host environments and indicating different potentials to infect humans. Thirty-two AMR genes were detected, susceptibility to 18 clinical used antibiotics including aminoglycoside, chloramphenicol, trimethoprim, and sulfa was checked to evaluate the availability of clinical medicines. Resistance to Rifampicin, Cefazolin, ceftazidime, Ampicillin, and ceftriaxone is prevalent in most strains, resistance to tetracycline, trimethoprim-sulfamethoxazole, ciprofloxacin, and levofloxacin are aggregated in nearly half of frog-derived strains, suggesting that drug resistance of frog-derived strains is more serious, and clinical treatment for L. hongkongensis infection should be more cautious.

Radiomics combined with clinical characteristics predicted the progression-free survival time in first-line targeted therapy for advanced non-small cell lung cancer with EGFR mutation.

OBJECTIVE: This study was to explore the most appropriate radiomics modeling method to predict the progression-free survival of EGFR-TKI treatment in advanced non-small cell lung cancer with EGFR mutations. Different machine learning methods may vary considerably and the selection of a proper model is essential for accurate treatment outcome prediction. Our study were established 176 discrimination models constructed with 22 feature selection methods and 8 classifiers. The predictive performance of each model were evaluated using the AUC, ACC, sensitivity and specificity, where the optimal model was identified. RESULTS: There were totally 107 radiomics features and 7 clinical features obtained from each patient. After feature selection, the top-ten most relevant features were fed to train 176 models. Significant performance variations were observed in the established models, with the best performance achieved by the logistic regression model using gini-index feature selection (AUC = 0.797, ACC = 0.722, sensitivity = 0.758, specificity = 0.693). The median R-score was 0.518 (IQR, 0.023-0.987), and the patients were divided into high-risk and low-risk groups based on this cut-off value. The KM survival curves of the two groups demonstrated evident stratification results (p = 0.000).

Buyang huanwu decoction combined with probiotics or prebiotics for functional recovery from stroke: A meta-analysis protocol for systematic review.

BACKGROUND: Stroke is a global disease that compromises human health. Considering the side effects of Western medicine, alternative medicine, such as Chinese medicine, is widely used. Concurrently, the research and development on the microbiota-gut-brain axis in recent years have made intestinal microflora the new target of treatment. We aim to scientifically evaluate the advantages and clinical guidance of using Buyang-Huanwu (BYHW) decoction combined with probiotics in the intestinal microflora. METHODS: The search will focus on published Randomized Controlled Trial (RCTs) that used BYHW decoction, probiotics, prebiotics, synbiotics, or similar microecological preparations to treat stroke. We will search for relevant studies in six databases: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Data, and Chongqing VIP Information. The retrieval date will be limited to the period from inception to June 2021 and will not be restricted by language. The extracted data will be subjected to systematic review and meta-analysis to evaluate its clinical advantages and efficacy. Patient-centred and most responsive outcomes will be selected as major outcomes, including the Fugl-Meyer (FMA) and Barthel scales. Secondary outcomes will be clinically assessed factors, including inflammatory factors in serum, platelet aggregation, other laboratory parameters, and the number and distribution of flora in the gut. We will evaluate the bias of each included study using the latest version of the Cochrane Handbook and the RoB tool. The analysis of all data and the drawing of forest maps will be performed using STAT 15.1 SE software. Regardless of the I2 values generated between the studies, we will perform a subgroup analysis. The grouping method will be based on all included research characteristics and factors that may cause heterogeneity, and may depend on differences in intervention methods, sources of subjects, and other relevant factors. RESULTS: We plan to present the results of this systematic review in a peer-reviewed scientific journal, conferences, and popular press. CONCLUSION: The efficacy and safety of Buyang-Huanwu decoction combined with probiotics for the treatment of stroke will be evaluated, and the conclusion will be published to provide medical evidence for a better clinical decision of patients with stroke.