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Liquid biopsy is emerging as a pivotal tool in precision oncology, offering a noninvasive and comprehensive approach to cancer diagnostics and management. By harnessing biofluids such as blood, urine, saliva, cerebrospinal fluid, and pleural effusions, this technique profiles key biomarkers including circulating tumor DNA, circulating tumor cells, microRNAs, and extracellular vesicles. This review discusses the extended scope of liquid biopsy, highlighting its indispensable role in enhancing patient outcomes through early detection, continuous monitoring, and tailored therapy. While the advantages are notable, we also address the challenges, emphasizing the necessity for precision, cost‐effectiveness, and standardized methodologies in its broader application. The future trajectory of liquid biopsy is set to expand its reach in personalized medicine, fueled by technological advancements and collaborative research. Liquid biopsy is transforming cancer diagnosis through noninvasive methods, detecting biomarkers in various biofluids. This review explores its growing role in early detection, continuous monitoring, and personalized therapy. While highlighting its benefits, we address challenges such as accuracy and accessibility and look toward future innovations for broader personalized medicine applications.

We previously reported on the strong symbiosis of AMF species ( Rhizophagus irregularis CD1) with the cotton ( Gossypium hirsutum L.) which is grown worldwide. In current study, it was thus investigated in farmland to determine the biological control effect of AMF on phosphorus acquisition and related gene expression regulation, plant growth and development, and a series of agronomic traits associated with yield and fiber quality in cotton. When AMF and cotton were symbiotic, the expression of the specific phosphate transporter family genes and P concentration in the cotton biomass were significantly enhanced. The photosynthesis, growth, boll number per plant and the maturity of the fiber were increased through the symbiosis between cotton and AMF. Statistical analysis showed a highly significant increase in yield for inoculated plots compared with that from the non inoculated controls, with an increase percentage of 28.54%. These findings clearly demonstrate here the benefits of AMF-based inoculation on phosphorus acquisition, growth, seed cotton yield and fiber quality in cotton. Further improvement of these beneficial inoculants on crops will help increase farmers’ income all over the world both now and in the future.

With rapid economic development, expressway traffic volumes have surged, resulting in severe congestion. To address this, expanding expressways to two-way ten-lane configurations has become a primary strategy for alleviating traffic pressure. Given the absence of unified national design standards for such highways, this study employs VISSIM microscopic traffic simulation integrated with the Surrogate Safety Assessment Model (SSAM) to investigate the relationship between speed change lane geometries and their design parameters. We evaluate the impacts of varying speed change lane lengths on traffic efficiency and safety under multiple traffic flow conditions for renovated two-way ten-lane expressways. Performance metrics include average delay time, average queue length, conflict frequency, and Post-Encroachment Time (PET). Results demonstrate that at a mainline design speed of 120 km/h, a 270-m acceleration lane reduces traffic conflicts by 47.6% compared to the conventional 230-m benchmark, while a 161-m deceleration lane achieves a 32.8% reduction. This research provides actionable design recommendations for optimizing speed change lane lengths on two-way ten-lane expressways, ultimately enhancing road capacity, safety, and traffic resource allocation efficiency.

Pseudorabies virus (PRV) can infect most mammals and is well known for causing substantial economic losses in the pig industry. In addition to pigs, PRV infection usually leads to severe itching, central nervous system dysfunction, and 100% mortality in its non-natural hosts. It should be noted that increasing human cases of PRV infection have been reported in China since 2017, and these patients have generally suffered from nervous system damage and even death. Here, we reviewed the current prevalence and variation in PRV worldwide as well as the PRV-caused infections in animals and humans, and briefly summarized the vaccines and diagnostic methods used for pseudorabies control. Most countries, including China, have control programs in place for pseudorabies in domestic pigs, and thus, the disease is on the decline; however, PRV is still globally epizootic and an important pathogen for pigs. In countries where pseudorabies in domestic pigs have already been eliminated, the risk of PRV transmission by infected wild animals should be estimated and prevented. As a member of the alphaherpesviruses, PRV showed protein-coding variation that was relatively higher than that of herpes simplex virus-1 (HSV-1) and varicella-zoster virus (VZV), and its evolution was mainly contributed to by the frequent recombination observed between different genotypes or within the clade. Recombination events have promoted the generation of new variants, such as the variant strains resulting in the outbreak of pseudorabies in pigs in China, 2011. There have been 25 cases of PRV infections in humans reported in China since 2017, and they were considered to be infected by PRV variant strains. Although PRV infections have been sporadically reported in humans, their causal association remains to be determined. This review provided the latest epidemiological information on PRV for the better understanding, prevention, and treatment of pseudorabies.

Objective To investigate the risk factors of left atrial thrombus (LAT)/spontaneous echo contrast (SEC) in patients with nonvalvular atrial fibrillation (AF). Methods This retrospective study analysed the data from consecutive patients with nonvalvular AF that underwent transoesophageal echocardiography. Logistic regression analysis was performed to identify risk factors of LAT/SEC. Receiver operating characteristic curve analysis was undertaken compare the new scales with CHADS2 and CHA2DS2-VASc scores. Results A total of 558 patients with AF were included in the study. LAT/SEC was detected in 137 (24.6%) patients. The independent risk factors of LAT/SEC beyond CHADS2 or CHA2DS2-VASc scores included non-paroxysmal AF and left atrial diameter >37.5 mm. These two variables were added into the CHADS2 or CHA2DS2-VASc score to build new scales. Areas under the curve for the new scales based on CHADS2 and CHA2DS2-VASc scores were significantly higher than the CHADS2 or CHA2DS2-VASc score both in the overall study cohort and in patients at a high risk of thromboembolism. Conclusions Non-paroxysmal AF and increased left atrial diameter beyond the CHADS2 or CHA2DS2-VASc score were independent risk factors of LAT/SEC and may help to improve the current risk stratification, especially for patients with nonvalvular AF at a high risk of thromboembolism.

Background Human bone marrow mesenchymal stem cells (hBMSCs) are a major source of osteoblast precursor cells and are directly involved in osteoporosis (OP) progression. Bromodomain-containing protein 4 (BRD4) is an important regulator for osteogenic differentiation. Therefore, its role and mechanism in osteogenic differentiation process deserve further investigation. Methods hBMSCs osteogenic differentiation was evaluated by flow cytometry, alkaline phosphatase assay and alizarin red staining. Western blot was used to test osteogenic differentiation-related proteins, BRD4 protein, WNT family members-4 (WNT4)/NF-κB-related proteins, and glycolysis-related proteins. Metabolomics techniques were used to detect metabolite changes and metabolic pathways. BRD4 and WNT4 mRNA levels were determined using quantitative real-time PCR. Dual-luciferase reporter assay and chromatin immunoprecipitation assay were performed to detect BRD4 and WNT4 interaction. Glycolysis ability was assessed by testing glucose uptake, lactic acid production, and ATP levels. Results After successful induction of osteogenic differentiation, the expression of BRD4 was increased significantly. BRD4 knockdown inhibited hBMSCs osteogenic differentiation. Metabolomics analysis showed that BRD4 expression was related to glucose metabolism in osteogenic differentiation. Moreover, BRD4 could directly bind to the promoter of the WNT4 gene. Further experiments confirmed that recombinant WNT4 reversed the inhibition effect of BRD4 knockdown on glycolysis, and NF-κB inhibitors (Bardoxolone Methyl) overturned the suppressive effect of BRD4 knockdown on hBMSCs osteogenic differentiation. Conclusion BRD4 promoted hBMSCs osteogenic differentiation by inhibiting NF-κB pathway via enhancing WNT4 expression.

BackgroundThe purpose of this study was to evaluate the impact of ipsilateral supraclavicular lymph node dissection (ISLND) on the outcomes of breast cancer patients with ipsilateral supraclavicular lymph node metastasis (ISLNM), and to evaluate the prognostic value of ipsilateral supraclavicular pathological complete response (ispCR). Meanwhile, a nomogram was constructed to predict ispCR.MethodsWe retrospectively reviewed the medical documents of 353 patients with ISLNM but no distant metastasis at presentation. Based on whether ISLND was performed, patients were divided into radiotherapy (RT) and ISLND + RT groups. The impact of ISLND was evaluated after propensity score matching, and the prognostic value of ispCR was also analyzed. A nomogram to predict the probability of ispCR was constructed based on clinicopathologic variables.ResultsAfter propensity score matching, we found that the use of ISLND was associated with a higher rate of ipsilateral supraclavicular relapse-free survival (ISRFS; p < 0.0001). Among 307 patients who underwent ISLND, ispCR was associated with a higher rate of ISRFS and disease-free survival (p = 0.018 and p = 0.00033, respectively). Furthermore, the nomogram constructed with number of axillary lymph node metastases, breast pCR, size of the ipsilateral supraclavicular lymph nodes after neoadjuvant chemotherapy (NAC), number of NAC cycles, and Ki67 level showed a good fit for predicting ispCR.ConclusionFor breast cancer patients with ISLNM but no distant metastasis, ISLND may be beneficial in some certain subtypes, and ispCR indicated a better prognosis. Our nomogram is well-fitted to predict the probability of achieving ispCR.

Objective To investigate the distribution, drug resistance and risk factors of multi-drug resistant bacterias (MDROs) in patients with Type 2 diabetic foot ulcers (DFU). Method The clinical data, foot secretions, pathogenic microorganisms and drug sensitivity tests of 147 patients with type 2 diabetes admitted to our department from January 2018 to December 2021 were analyzed. Patients were divided into two groups according to whether they had been infected with MDROs or not. Seventy-one cases were infected with MDROs as the case group, and the remaining 76 cases were the control group. Chi-square test and t-test were used to analyze the results of MDROs infection and DFU, and logistic multivariate regression was used to evaluate the risk factors of MDROs infection. Results A total of 71 strains were isolated from the MDROs-positive group, with the top three being Staphylococcus aureus (46.48%), Escherichia coli (22.53%), and Pseudomonas aeruginosa (18.31%), respectively. Logistic multifactorial regression analysis showed that history of previous antimicrobial exposure, neuroischemic wound, Wagner grade 3-5, and combined osteomyelitis were associated with Type 2 diabetic foot infection MDROs (P<0.05). Conclusion Previous history of antimicrobial exposure, neuroischemic wounds, Wagner grade 3-5, and combined osteomyelitis are independent risk factors for MDROs, which can identify the risk factors for MDROs at an early stage and help to identify people at high risk of MDROs infection and take relevant comprehensive treatment in time to slow down the development of the disease.

Marine cyclopianes are a family of diterpenoid with novel carbon skeleton and diverse biological activities. Herein, we report our synthetic and chemical proteomics studies of cyclopiane diterpenes which culminate in the asymmetric total synthesis of conidiogenones C, K and 12β-hydroxy conidiogenone C, and identification of Immunity-related GTPase family M protein 1 (IRGM1) as a cellular target. Our asymmetric synthesis commences from Wieland-Miescher ketone and features a sequential intramolecular Pauson-Khand reaction and gold-catalyzed Nazarov cyclization to rapidly construct the 6-5-5-5 tetracyclic skeleton. The stereocontrolled cyclopentenone construction is further investigated on complex settings to demonstrate its synthetic utility. Furthermore, using an alkyne-tagged conidiogenone C-derived probe, IRGM1, a master regulator of type I interferon responses, is identified as a key cellular target of conidiogenone C responsible for its anti-inflammatory activity. Preliminary mechanism of action studies shows that conidiogenone C activates IRGM1-mediate dysfunctional mitochondria autophagy to maintain mitochondria quality control of inflammatory macrophages. The cyclopiane diterpenoids are a class of complex natural products with unique carbon skeleton and diverse biological activities. Herein, the authors report the total synthesis and chemical proteomics studies of cyclopiane diterpenes which culminate in the asymmetric total synthesis of conidiogenones C, K and 12β-hydroxy conidiogenone C, and identification of Immunity-related GTPase family M protein 1 as a cellular target of conidiogenone C.

Purified from the roots of the plant Sinomenium acutum, sinomenine is traditionally used in China and Japan for treating rheumatism and arthritis. Previously, we have demonstrated that sinomenine possessed a broad analgesic spectrum in various chronic pain animal models and repeated administration of sinomenine did not generate tolerance. In this review article, we discussed sinomenine’s analgesic mechanism with focus on its role on immune regulation and neuroimmune interaction. Sinomenine has distinct immunoregulative properties, in which glutamate, adenosine triphosphate, nitric oxide, and proinflammatory cytokines are thought to be involved. Sinomenine may alter the unbalanced neuroimmune interaction and inhibit neuroinflammation, oxidative stress, and central sensitization in chronic pain states. In conclusion, sinomenine has promising potential for chronic pain management in different clinical settings.