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BackgroundColorectal cancer (CRC) is one of the most commonly diagnosed advanced-stage malignancies worldwide and places a substantial burden on both the economic and social development of numerous countries.ObjectiveThis manuscript aims to synthesize the existing evidence and explore potential avenues for future scholarly research on ctDNA in CRC.MethodsBibliometric analyses were performed using the bibliometrix package in R, along with CiteSpace and VOSviewer software. The search was restricted to publications up to 31 March 2024, using the following terms: (“ctDNA” OR “circulating tumor DNA”) AND (“colorectal cancer” OR “colorectal tumor”) from the Web of Science Core Collection (WoSCC) database.ResultsUltimately, we identified 1,310 documents published in 353 journals authored by 7,683 researchers from 2,417 institutions across 66 countries. The USA was the most productive country. The Journal of Clinical Oncology was the most prolific, publishing 111 articles with 3,396 citations. The top five keywords were “colorectal cancer,” “circulating tumor DNA,” “acquired resistance,” “cell-free DNA,” and “plasma.” The top five cluster labels for references were “advanced cancer,” “metastatic colorectal cancer,” “liquid biopsy,” “colorectal cancer,” and “human colorectal cancer xenograft.”ConclusionsThe collaborative networks are primarily composed of highly productive authors, prestigious institutions, and leading countries. Additionally, the advancement of detection technologies, the development of standardized protocols, the exploration of circulating tumor DNA (ctDNA) dynamics in CRC, and the implementation of large-scale clinical trials for ctDNA-guided precision therapy in CRC are expected to become major research priorities in the future.

BackgroundCatastrophic Antiphospholipid Syndrome (CAPS), a severe systemic autoimmune disorder, predominantly causes life-threatening multi-organ failure, with a high mortality rate. It primarily affects small vessels, seldom impacting large vessels. Notably, acute massive pulmonary embolism (PE) with bilateral atrial thrombosis is an exceptional occurrence in CAPS. Acute pulmonary embolism (PE) is a common cardiovascular disease that progresses rapidly and has a high mortality rate. Acute massive PE combined with bilateral atrial thrombosis has an even higher mortality rate. PE treatments primarily include pharmaceuticals, catheter interventions, and surgical measures, with integrated treatment strategies demonstrating promising outcomes in clinical practice. Extracorporeal membrane oxygenation (ECMO) can provide cardiopulmonary support for the treatment of high-risk PE patients and is a proven therapeutic measure.MethodsThis report presents the case of a 52-year-old male admitted due to fever and sudden onset of impaired consciousness, with cardiac ultrasound and pulmonary artery CT angiography revealing an acute large-scale pulmonary embolism accompanied by bilateral atrial thrombosis, with the condition rapidly worsening and manifesting severe respiratory and circulatory failure. With ECMO support, the patient underwent a thrombectomy using an AngioJet intervention. The diagnosis of CAPS was confirmed through clinical presentation and laboratory examination, and treatment was adjusted accordingly.ResultsThe patient made a successful recovery and was subsequently discharged from the hospital.ConclusionIn CAPS patients, the rare instance of acute massive PE accompanied by bilateral atrial thrombosis significantly risks severe respiratory and circulatory failure, adversely affecting prognosis. Early initiation of ECMO therapy is crucial, offering a vital opportunity to address the root cause. In this case report the patient was successfully treated with an AngioJet thrombectomy supported by ECMO.

BackgroundSome bacteria enter the viable but non-culturable (VBNC) state to survive harsh environmental conditions and external stresses. This alters cell physiology and has implications for the food industry as some bacteria, such as lactobacilli, undergo similar changes during food processing.MethodsThis study aimed to investigate the transcriptomic changes of a probiotic strain, Lacticaseibacillus paracasei Zhang (L. paracasei Zhang), upon transition to the VBNC state using high throughput RNA sequencing (RNA-seq).ResultsBacteria were inoculated into the de Man, Rogosa, and Sharpe medium and maintained at low temperature and pH to induce cell transition to the VBNC state. Cells were harvested for analysis at five stages of VBNC induction: 0, 3, 30, and 180 days after induction and 210 days when the cells entered the VBNC state. Our results showed that the expression of 2,617, 2,642, 2,577, 2,829, and 2,840 genes was altered at these five different stages. The function of differentially expressed genes (DEGs, compared to healthy cells collected at day 0) and their encoded pathways were analyzed by the Gene Ontology Consortium and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. A total of 10 DEGs were identified in cells that entered the VBNC state: five continuously upregulated (LCAZH_0621, LCAZH_1986, LCAZH_2038, LCAZH_2040, and LCAZH_2174) and five continuously downregulated (LCAZH_0024, LCAZH_0210, LCAZH_0339, LCAZH_0621, and LCAZH_0754).ConclusionsThis study proposes a molecular model of the VBNC mechanism in L. paracasei Zhang, highlighting that changes in cell metabolism improve substrate utilization efficiency, thereby enhancing bacterial survival under adverse conditions. These data may be useful for improving the survival of probiotics in industrial food processing.

Background and objectivesNationwide data were used to explore factors associated with physical function in order to identify interventions that could improve and maintain physical function in the older people.MethodsThe physical function was assessed by gait speed (GS). We selected 2,677 male and 2,668 female older adults (aged ≥60) who could perform the GS test as study subjects. GS was measured by having subjects walk across and back a 10-m course. A gait speed less than 20% that of a reference population (

BackgroundAny form of physical activity is recommended for the older adults to maintain their physical function; however, the effect of daily activities on muscle function still needs to be investigated. Humans always use one dominant hand to perform tasks, providing a natural situation for research on the effect of daily activities on muscle function.MethodsFive hundred and twenty-six healthy adults were recruited from the community in Beijing. Muscle strength was assessed using a handgrip dynamometer, lean mass, fat mass, bone area and bone mineral content of upper limbs were assessed using dual-energy X ray-absorptiometry. The results were compared between the dominant and non-dominant upper limbs.ResultsThe dominant upper limb had better muscle strength, lean mass, bone area and bone mineral content than the non-dominant side. The difference in muscle strength and lean mass between the two upper limbs decreased with the advanced age. In older age, fat mass of upper limbs increased in men, but not in women.ConclusionDaily activities can maintain better muscle function in the dominant upper limb than in the non-dominant side; however, the delaying effect on age-related decline in muscle function was limited.

Hand, foot, and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) infection, currently lacks specific preventive and therapeutic interventions. Here, we demonstrated that Pien Tze Huang (PZH) could dose-dependently inhibit EV-A71 replication at the cellular level, resulting in significant reductions in EV-A71 virus protein 1 (VP1) expression and viral yields in Vero and human rhabdomyosarcoma cells. More importantly, we confirmed that PZH could protect mice from EV-A71 infection for the first time, with Ribavirin serving as a positive control. PZH treatment reduced EV-A71 VP1 protein expression, viral yields in infected muscles, and improved muscle pathology. Additionally, we conducted a preliminary mechanism study using quantitative proteomics. The results suggested that the suppression of the PI3K/AKT/mTOR and NF-κB signaling pathways may contribute to the anti-EV-A71 activity of PZH. These findings provide strong evidence supporting the potential therapeutic application of PZH for EV-A71 infection management.

BackgroundApolipoprotein E (APOE) ε2 and APOE ε4 are the most distinct alleles among the three APOE alleles, both structurally and functionally. However, differences in cognition, brain function, and brain structure between the two alleles have not been comprehensively reported in the literature, especially in non-demented elderly individuals.MethodsA neuropsychological test battery was used to evaluate the differences in cognitive performance in five cognitive domains. Independent component analysis (ICA) and voxel-based morphometry (VBM) were used separately to analyze resting-state functional magnetic resonance imaging (rs-fMRI) data and the structure MRI data between the two groups. Finally, correlations between differential brain regions and neuropsychological tests were calculated.ResultsAPOE ε2 carriers had better cognitive performance in general cognitive, memory, attention, and executive function than APOE ε4 carriers (all p

BackgroundDiabetes mellitus (DM), a metabolic disease that has attracted significant research and clinical attention over the years, can affect the eye structure and induce cataract in patients diagnosed with DM. Recent studies have indicated the relationship between glycoprotein non-metastatic melanoma protein B (GPNMB) and DM and DM-related renal dysfunction. However, the role of circulating GPNMB in DM-associated cataract is still unknown. In this study, we explored the potential of serum GPNMB as a biomarker for DM and DM-associated cataract.MethodsA total of 406 subjects were enrolled, including 60 and 346 subjects with and without DM, respectively. The presence of cataract was evaluated and serum GPNMB levels were measured using a commercial enzyme-linked immunosorbent assay kit.ResultsSerum GPNMB levels were higher in diabetic individuals and subjects with cataract than in those without DM or cataract. Subjects in the highest GPNMB tertile group were more likely to have metabolic disorder, cataract, and DM. Analysis performed in subjects with DM elucidated the correlation between serum GPNMB levels and cataract. Receiver operating characteristic (ROC) curve analysis also indicated that GPNMB could be used to diagnose DM and cataract. Multivariable logistic regression analysis illustrated that GPNMB levels were independently associated with DM and cataract. DM was also found to be an independent risk factor for cataract. Further surveys revealed the combination of serum GPNMB levels and presence of DM was associated with a more precise identification of cataract than either factor alone.ConclusionsIncreased circulating GPNMB levels are associated with DM and cataract and can be used as a biomarker of DM-associated cataract.

In this paper, the Mohand transform-based homotopy perturbation method is proposed to solve two-dimensional linear and non-linear shallow water wave equations. This approach has been proved suitable for a broad variety of non-linear differential equations in science and engineering. The variation trend of the water surface elevation at different time levels and depths are given by some graphs. Moreover, the obtained solutions are compared with the existing results, which show higher efficiency and fewer computations than other approaches studied in the literature.

Antivirulence strategy has been developed as a nontraditional therapy which would engender a lower evolutionary pressure toward the development of antimicrobial resistance. However, the majority of the antivirulence agents currently in development could not meet clinical needs due to their narrow antibacterial spectrum and limited indications. Therefore, our main purpose is to develop broad-spectrum antivirulence agents that could target on both Gram-positive and Gram-negative pathogens. We discovered ML364, a novel scaffold compound, could inhibit the productions of both pyocyanin of Pseudomonas aeruginosa and staphyloxanthin of Staphylococcus aureus. Further transcriptome sequencing and enrichment analysis showed that the quorum sensing (QS) system of pathogens was mainly disrupted by ML364 treatment. To date, autoinducer-2 (AI-2) of the QS system is the only non-species-specific signaling molecule that responsible for the cross-talk between Gram-negative and Gram-positive species. And further investigation showed that ML364 treatment could significantly inhibit the sensing of AI-2 or its nonborated form DPD signaling in Vibrio campbellii MM32 and attenuate the biofilm formation across multi-species pathogens including Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus. The results of molecular docking and MM/GBSA free energy prediction showed that ML364 might have higher affinity with the receptors of DPD/AI-2, when compared with DPD molecule. Finally, the in vivo study showed that ML364 could significantly improve the survival rates of systemically infected mice and attenuate bacterial loads in the organs of mice. Overall, ML364 might interfere with AI-2 quorum sensing system to exert broad-spectrum antivirulence effect both in vitro and in vivo.

Ribonucleoside monophosphates are inevitably misincorporated into the DNA genome inside cells, and they need to be excised to avoid chromosome instability. Ribonucleases H (RNases H) are enzymes that specifically hydrolyze the RNA strand of RNA/DNA hybrids or the RNA moiety from DNA containing a stretch of RNA, they therefore are required for DNA integrity. Extensive studies have drawn a mostly clear picture of the mechanisms of RNase H catalysis, but some questions are still lacking definitive answers. This review summarizes three alternative models of RNase H catalysis. The two-metal model is prevalent, but a three-metal model suggests the involvement of a third cation in catalysis. Apparently, the mechanisms underlying metal-dependent hydrolyzation are more complicated than initially thought. We also discuss the metal choices of RNases H and analyze how chemically similar cations function differently. Substrate and cleavage-site specificities vary among RNases H, and this is explicated in detail. An intriguing phenomenon is that organisms have diverse RNase H combinations, which may provide important hints to how rnh genes were transferred during evolution. Whether RNase H is essential for cellular growth, a key question in the study of in vivo functions, is also discussed. This article may aid in understanding the mechanisms underlying RNase H and in developing potentially promising applications of it.

Green merger and acquisition (Green M&A) is one of the ways of corporate environmental investment, which is vital for their green transformation and sustainable development. With the implementation of the newly revised Environmental Protection Law in 2015, this paper investigates the impact of environmental regulation on corporate green M&A using the Difference-in-Difference method with a sample of Chinese listed companies from 2007 to 2020. We found that firms’ green M&A increases significantly after the implementation of the new Environmental Protection Law. The promotion effect is more pronounced when the firm is state-owned or faces lower financing constraints. Further analysis reveals that green M&A significantly reduces firms’ environmental management costs, enhances green innovation, and has no effect on market performance. This result confirms that after the implementation of the new Environmental Protection Law, companies engage in green M&A for cost and innovation motives rather than market motives.

BackgroundCommensal microbiota have been proven to colonize the mammary gland, but whether their composition is altered in patients with breast cancer (BC) remains elusive. This study intends to explore the breast microbiome differences between benign and malignant diseases and to investigate the impact of neoadjuvant chemotherapy (NAC) on the breast microbiota in patients with BC.MethodsBreast normal adipose tissues (NATs) were collected from 79 patients with BC and 15 controls between July 2019 and November 2021. The BC group consisted of 29 patients who had received NAC and 50 who were non-NAC patients. Participants diagnosed with benign breast disease were recruited as controls. 16S rRNA gene sequencing was used to analyze the bacterial diversity of NATs.ResultsThe community structure of the NAT microbiome was significantly different between the BC and control groups. Proteobacteria decreased (47.40% versus 39.74%), whereas Firmicutes increased (15.71% versus 25.33%) in patients with BC when compared with that in control tissues. Nine genera were enriched in BC NATs, and four genera levels increased in the control group. The associations between differential bacterial genera and breast tumor grade were calculated by Spearman’s correlation. The results showed that tumor grade was positively associated with the relative abundance of Streptococcus and negatively related to Vibrio, Pseudoalteromonas, RB41, and Photobacterium. Moreover, menopause was associated with the microbiota composition change of non-NAC BC patients and related to the significant reduction in the abundance level of Pseudoalteromonas, Veillonella, and Alcaligenes. In addition, NAC was related to the beta diversity of patients with BC and associated with the decrease of Clostridium_sensu_stricto_7 and Clostridium_sensu_stricto_2 in postmenopausal patients. Of note, Tax4Fun functional prediction analysis revealed that the metabolic state was more exuberant in the BC group with upregulating of multiple metabolism-related pathways.ConclusionOur results offer new insight into the relationship between NAC and breast microbiota and help to better characterize the breast microbial dysbiosis that occurs in patients with BC. Further epidemiological studies with larger sample size and well-designed animal experiments are required to elucidate the role of breast microbiota in the therapeutic outcome of BC.

The increasing spread of drug-resistant bacterial strains presents great challenges to clinical antibacterial treatment and public health, particularly with regard to β-lactamase-producing Enterobacteriaceae. A rapid and accurate detection method that can expedite precise clinical diagnostics and rational administration of antibiotics is urgently needed. Targeted proteomics, a technique involving selected reaction monitoring or multiple reaction monitoring, has been developed for detecting specific peptides. In the present study, a rapid single-colony-processing procedure combined with an improved parallel reaction monitoring (PRM) workflow based on HRAM Orbitrap MS was developed to detect carbapenemases (Klebsiella pneumoniae carbapenemase, KPC; imipenemase, IMP; Verona integron-encoded metallo-β-lactamase, VIM; New Delhi metallo-β-lactamase, NDM; and oxacillinase, OXA), extended spectrum β-lactamases (TEM and CTX-M), and AmpC (CMY-2) produced by Enterobacteriaceae. Specific peptides were selected and validated, and their coefficients of variation and stability were evaluated. In total, 188 Enterobacteriaceae strains were screened using the workflow. Fourteen out of total 19 peptides have 100% specificity; three peptides have specificity >95% and two peptides have specificity ranged from 74∼85%. On the sensitivity, only nine peptides have 95∼100% sensitivity. The other 10 peptides have sensitivity ranged from 27∼94%. Thus, a screening method based on peptide groups was developed for the first time. Taken together, this study described a rapid extraction and detection workflow for widespread β-lactamases, including KPC, IMP, VIM, NDM, OXA, CMY, CTX-M, and TEM, using single colonies of Enterobacteriaceae strains. PRM-targeted proteomics was proven to be a promising approach for the detection of drug-resistant enzymes.

The realization of many protein functions is inseparable from the interaction with ligands; in particular, the combination of protein and metal ion ligands performs an important biological function. Currently, it is a challenging work to identify the metal ion ligand-binding residues accurately by computational approaches. In this study, we proposed an improved method to predict the binding residues of 10 metal ion ligands (Zn2+, Cu2+, Fe2+, Fe3+, Co2+, Mn2+, Ca2+, Mg2+, Na+, and K+). Based on the basic feature parameters of amino acids, and physicochemical and predicted structural information, we added another two features of amino acid correlation information and binding residue propensity factors. With the optimized parameters, we used the GBM algorithm to predict metal ion ligand-binding residues. In the obtained results, the Sn and MCC values were over 10.17% and 0.297, respectively. Besides, the Sn and MCC values of transition metals were higher than 34.46% and 0.564, respectively. In order to test the validity of our model, another method (Random Forest) was also used in comparison. The better results of this work indicated that the proposed method would be a valuable tool to predict metal ion ligand-binding residues.

Background: Apolipoprotein E (APOE) ε2 and APOE ε4 are the most distinct alleles among the three APOE alleles, both structurally and functionally. However, differences in cognition, brain function, and brain structure between the two alleles have not been comprehensively reported in the literature, especially in non-demented elderly individuals. Methods: A neuropsychological test battery was used to evaluate the differences in cognitive performance in five cognitive domains. Independent component analysis (ICA) and voxel-based morphometry (VBM) were used separately to analyze resting-state functional magnetic resonance imaging (rs-fMRI) data and the structure MRI data between the two groups. Finally, correlations between differential brain regions and neuropsychological tests were calculated. Results: APOE ε2 carriers had better cognitive performance in general cognitive, memory, attention, and executive function than APOE e4 carriers (all p < 0.05). In ICA analyses of rs-fMRI data, the difference in the resting-state functional connectivity (rsFC) between two groups is shown in 7 brain networks. In addition, VBM analyses of the T1-weighted image revealed that APOE ε2 carriers had a larger thalamus and right postcentral gyrus volume and a smaller bilateral putamen volume than APOE e4 carriers. Finally, differences in brain function and structure may be the reason that APOE ε2 carriers are better than APOE ε4 carriers in cognitive performance. Conclusion: These findings suggest that there are significant differences in brain function and structure between APOE ε2 carriers and APOE ε4 carriers, and these significant differences are closely related to their cognitive performance. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM), a metabolic disease that has attracted significant research and clinical attention over the years, can affect the eye structure and induce cataract in patients diagnosed with DM. Recent studies have indicated the relationship between glycoprotein non-metastatic melanoma protein B (GPNMB) and DM and DM-related renal dysfunction. However, the role of circulating GPNMB in DM-associated cataract is still unknown. In this study, we explored the potential of serum GPNMB as a biomarker for DM and DM-associated cataract. Methods: A total of 406 subjects were enrolled, including 60 and 346 subjects with and without DM, respectively. The presence of cataract was evaluated and serum GPNMB levels were measured using a commercial enzyme-linked immunosorbent assay kit. Results: Serum GPNMB levels were higher in diabetic individuals and subjects with cataract than in those without DM or cataract. Subjects in the highest GPNMB tertile group were more likely to have metabolic disorder, cataract, and DM. Analysis performed in subjects with DM elucidated the correlation between serum GPNMB levels and cataract. Receiver operating characteristic (ROC) curve analysis also indicated that GPNMB could be used to diagnose DM and cataract. Multivariable logistic regression analysis illustrated that GPNMB levels were independently associated with DM and cataract. DM was also found to be an independent risk factor for cataract. Further surveys revealed the combination of serum GPNMB levels and presence of DM was associated with a more precise identification of cataract than either factor alone. Conclusions: Increased circulating GPNMB levels are associated with DM and cataract and can be used as a biomarker of DM-associated cataract. [ABSTRACT FROM AUTHOR]

Background: Transcatheter closure of paravalvular leak (PVL) has evolved into an alternative to surgery in high-risk patients. In this study, we introduce a new access for transcatheter closure of PVL and seek to evaluate the feasibility and safety of this access.Methods: We retrospectively analyzed patients undergoing transbrachial access for transcatheter mitral or aortic PVL closure (August 2017–November 2019) at our hospital. All patients underwent puncture of the brachial artery under local anesthesia.Results: The study population included 11 patients, with an average age of 55.91 ± 14.82 years. Ten out of 11 patients were successfully implanted with devices via the brachial artery approach, and one patient was converted to the transseptal approach. The technical success rate of transbrachial access was 90.9%. Mean NYHA functional class improved from 3.1 ± 0.5 before the procedure to 1.9 ± 0.5 after PVL closure. Severe paravalvular regurgitation (PVR) in five patients and moderate PVR in six patients prior to the procedure were significantly reduced to mild in four patients and none in seven patients after the procedure. Complications included one case of pseudoaneurysm and one case of moderate hemolysis aggravation after closure. One patient had an unknown cause of sudden death within 24 h after the procedure. The half-year mortality rate during follow-up was 9.1% (1/11).Conclusions: Transbrachial access for transcatheter closure of PVL may be a feasible and safe treatment and should include well-selected patients. It has several potential advantages of simplifying the procedure process and reducing postprocedural bed rest time.