Enhancing Sensitivity in Detecting Severe Fever With Thrombocytopenia Syndrome Virus: Development of a Reverse Transcription-Droplet Digital Polymerase Chain Reaction.

Severe fever with thrombocytopenia syndrome (SFTS) is a highly fatal disease. Droplet digital polymerase chain reaction (ddPCR) presents unparalleled sensitivity and enables absolute quantification of viral load. In this prospective study, we enrolled 111 patients with SFTS and collected 259 continuous samples. Our findings unveil a robust reverse transcription (RT)-ddPCR method for SFTS with a limit of detection of 2.46 copies/µL (95% CI, 1.50-11.05), surpassing the sensitivity of RT-quantitative polymerase chain reaction at 103.29 copies/µL (95% CI, 79.69-216.35). Longitudinal cohort analysis revealed significantly higher RT-ddPCR detection rates at days 10 to 11, 13 to 14, and ≥15 of the disease course as compared with RT-quantitative polymerase chain reaction (P < .05). Positive RT-ddPCR results were associated with declined platelet and elevated aspartate aminotransferase and lactate dehydrogenase on the same day vs negative RT-ddPCR samples. RT-ddPCR exhibits commendable diagnostic efficacy in SFTS, and it remains detectable in blood samples from patients with an extended disease course. Furthermore, RT-ddPCR correlates with clinical laboratory tests, furnishing valuable reference data for clinical diagnosis.

Retrospective analysis of patients with hepatocellular carcinoma complicated with human immunodeficiency virus infection after hepatectomy.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide, with a 5-year relative survival rate of approximately 18%. The similarity between incidence and mortality (830000 deaths per year) underscores the bleak prognosis associated with the disease. HCC is the fourth most common malignancy and the second leading cause of cancer death in China. Most patients with HCC have a history of chronic liver disease such as chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, alcoholism or alcoholic steatohepatitis, nonalcoholic fatty liver disease, or nonalcoholic steatohepatitis. Early diagnosis and effective treatment are the keys to improving the prognosis of patients with HCC. Although the total number of human immunodeficiency virus (HIV)-infected patients is declining globally the incidence of HCC is increasing in HIV-infected patients, especially those who are coinfected with HBV or HCV. As a result, people infected with HIV still face unique challenges in terms of their risk of developing HCC. AIM: To investigate the survival prognosis and clinical efficacy of surgical resection in patients with HCC complicated with HIV infection. METHODS: The clinical data of 56 patients with HCC complicated with HIV admitted to the Third Affiliated Hospital of Nantong University from January 2013 to December 2023 were retrospectively analyzed. Among these, 27 patients underwent hepatectomy (operation group) and 29 patients received conservative treatment (nonoperation group). All patients signed informed consents in line with the provisions of medical ethics. The general data, clinicopathological features and prognoses for the patients in the two groups were analyzed and the risk factors related to the prognoses of the patients in the operation group were identified. RESULTS: The median disease-free survival (DFS) and overall survival (OS) of HIV-HCC patients in the surgical group were 13 months and 17 months, respectively, and the median OS of patients in the nonsurgical group was 12 months. The OS of the surgical group was significantly longer than that of the control group (17 months vs 12 months, respectively; P < 0.05). The risk factors associated with DFS and OS in the surgical group were initial HIV diagnosis, postoperative microvascular invasion (MVI), a CD4+ T-cell count < 200/µL, Barcelona stage C-D, and men who have sex with men (MSM; P < 0.05). CONCLUSION: Hepatectomy can effectively prolong the survival of patients with HIV-HCC but MVI identified during postoperative pathological examination, late tumor detection, late BCLC stage, CD4+ T < 200/µL and MSM are risk factors affecting the survival and prognosis of patients undergoing hepatectomy. In addition, there were significant differences between the surgical group and the nonsurgical group in terms of the initial diagnosis of HIV, Child-Pugh score, alpha-fetoprotein measurement value, and HART-efficient antiretroviral therapy after the diagnosis of HIV (P < 0.05). Therefore, these factors may also affect the survival and prognosis of patients.

Predictive Value of CCQ and its Subdomains for Hospitalized Exacerbations in Chronic Obstructive Pulmonary Disease: A 3-Year Observational Prospective Study.

BACKGROUND: The prediction capacity of the Clinical COPD Questionnaire (CCQ) and its functional, symptom, and mental subdomain for COPD hospitalized exacerbation were rarely studied. OBJECTIVE: To examine the prognostic capacity of the total CCQ and its three subdomains for 3-year COPD hospitalized exacerbations. METHODS: We analyzed the predictive ability of total CCQ score and its subdomains for hospitalized exacerbations in an observational cohort of 987 subjects with stable COPD from the RealDTC, an ongoing multicenter prospective study. Hospitalized exacerbations were prospectively collected every 6 month for a maximum of 3 years. RESULTS: The total CCQ and its functional and symptom domain, but not the mental domain, were significantly associated with 3-year hospitalized exacerbations by multivariate Cox regression analysis. The predictive capacity of functional domain was similar to that of the total CCQ, but significantly stronger than the symptom and mental domain by ROC analysis (P < 0.05). ROC curves also showed that the AUC of exacerbation history combined with CCQ functional domain was larger than that of exacerbation history alone (P < 0.0001). Additionally, the predictive value of multivariable models that contains CCQ functional domain was significantly better than the corresponding model without CCQ functional domain (P < 0.05). CONCLUSIONS: The total CCQ and its functional and symptom domain were independent risk factors of 3-year hospitalized exacerbations. The prognostic capacity of the functional domain was similar to that of total CCQ, and was significantly stronger than the symptom and mental domain. The CCQ functional domain was able to increase the predictive power of exacerbation history and other multivariable prediction models, indicating it may have an important role in the multivariable prediction tool for hospitalized exacerbation, and its combination with other clinical variables might be used as a low-cost approach for assessments of the disease severity and severe exacerbation in COPD patients in the future.

Prediction of s

Motivated by the recently reported signatures of superconductivity in trilayer La_{4}Ni_{3}O_{10} under pressure, we comprehensively study this system using ab initio and random-phase approximation techniques. Without electronic interactions, the Ni d_{3z^{2}-r^{2}} orbitals show a bonding-antibonding and nonbonding splitting behavior via the O p_{z} orbitals inducing a "trimer" lattice in La_{4}Ni_{3}O_{10}, analogous to the dimers of La_{3}Ni_{2}O_{7}. The Fermi surface consists of three electron sheets with mixed e_{g} orbitals, and a hole and an electron pocket made up of the d_{3z^{2}-r^{2}} orbital, suggesting a Ni two-orbital minimum model. In addition, we find that superconducting pairing is induced in the s^{±}-wave channel due to partial nesting between the M=(π,π) centered pockets and portions of the Fermi surface centered at the Γ=(0,0) point. With changing electronic density n, the s^{±} instability remains leading and its pairing strength shows a domelike behavior with a maximum around n=4.2 (∼6.7% electron doping). The superconducting instability disappears at the same electronic density as that in the new 1313 stacking La_{3}Ni_{2}O_{7}, correlated with the vanishing of the hole pocket that arises from the trilayer sublattice, suggesting that the high-T_{c} superconductivity of La_{3}Ni_{2}O_{7} does not originate from a trilayer and monolayer structure. Furthermore, we confirm the experimentally proposed spin state in La_{4}Ni_{3}O_{10} with an in-plane (π, π) order and antiferromagnetic coupling between the top and bottom Ni layers, and spin zero in the middle layer.

Impact of exacerbation history on future risk and treatment outcomes in chronic obstructive pulmonary disease patients: A prospective cohort study based on Global Initiative for Chronic Obstructive Lung Disease (GOLD) A and B classifications.

Background: In this study, we aimed to explore the impact of exacerbation history on future exacerbation and mortality with different inhaled drugs in chronic obstructive pulmonary disease (COPD) patients based on a Global Initiative Chronic Obstructive Lung Disease (GOLD) A and B classifications. Methods: This observational study was based on the cohort study Real World Research of Diagnosis and Treatment of COPD (RealDTC). We collected data from COPD patients in China from 1 July 2017 to 31 December 2022. Patients were followed up until December 2023 or death. Further, we separated GOLD A and B patients into GOLD A0 and B0, who had no exacerbation during the previous year, and GOLD A1 and B1, who had only one exacerbation during the previous year. Study outcomes included moderate-to-severe exacerbation, hospitalisation, frequent exacerbation in the first year and all-cause mortality during total follow-up. Results: Of the 8318 eligible patients, GOLD E group of patients suffered from a greater risk of exacerbation in the first year and death than patients in the GOLD A and B groups. GOLD A1 group had a higher risk of moderate-to-severe exacerbation (hazard ratio (HR) = 2.087; 95% confidence interval (CI) = 1.419-3.068), hospitalisation (HR = 1.704; 95% CI = 1.010-2.705) and frequent exacerbation (HR = 1.983; 95% CI = 1.046-3.709) compared to GOLD A0. GOLD B1 group had a risk of moderate-to-severe exacerbation (HR = 1.321; 95% CI = 1.105-1.679) and mortality (HR = 1.362; 95% CI = 1.026-1.963) that exceeded the risk in GOLD B0 group. The treatment outcome of different inhaled drugs had no statistical differences in GOLD A0 group. In GOLD A1 group, only inhaled corticosteroids (ICS), in addition to long-acting ß-2 agonist (LABA) and long-acting muscarinic antagonist (LAMA), reduced the risk of moderate-to-severe exacerbation in the first year compared to only LAMA. As for the GOLD B0 group, LABA and LAMA decreased the odds of moderate-to-severe exacerbation, hospitalisation, frequent exacerbation and mortality compared to only LAMA. ICS, LABA, and LAMA in GOLD B0 also down-regulated the risk of frequent exacerbation, compared to only LAMA. In addition, GOLD B1 patients treated with LABA and LAMA or ICS, LABA, and LAMA had a lower risk of moderate-to-severe exacerbation and hospitalisation. Meanwhile, ICS, LABA, and LAMA also reduced the risk of frequent exacerbation and mortality, compared to only LAMA in the multivariate Cox analysis. Conclusions: Compared to the GOLD A or B group without exacerbation history, GOLD A patients with exacerbation history had a higher risk of future exacerbation, and GOLD B patients with exacerbation history had a higher risk of future exacerbation and mortality and benefited more from triple inhaler therapy.

Exploring public opinion on health effects of prepared dishes in China through social media comments.

Introduction: In the 2020s, particularly following 2022, the Chinese government introduced a series of initiatives to foster the development of the prepared dishes sector, accompanied by substantial investments from industrial capital. Consequently, China's prepared dishes industry has experienced rapid growth. Nevertheless, this swift expansion has elicited varied public opinions, particularly concerning the potential health effects of prepared dishes. Therefore, this study aims to gather and analyze comments from social media on prepared dishes using machine learning techniques. The objective is to ascertain the perspectives of the Chinese populace on the health implications of consuming prepared dishes. Methods: Social media comments, characterized by their broad distribution, objectivity, and timeliness, served as the primary data source for this study. Initially, the data underwent preprocessing to ensure its suitability for analysis. Subsequent steps in this study involved conducting sentiment analysis and employing the BERTopic model for topic clustering. These methods aimed to identify the principal concerns of the public regarding the impact of prepared dishes on health. The final phase of the study involved a comparative analysis of changes in public sentiment and thematic focus across different time frames. This approach provides a dynamic view of evolving public perceptions related to the health implications of prepared dishes. Results: This study analyzed over 600,000 comments gathered from various social media platforms from mid-July 2022 to the end of March 2024. Following data preprocessing, 200,993 comments were assessed for sentiment, revealing that more than 64% exhibited negative emotions. Subsequent topic clustering using the BERTopic model identified that 11 of the top 50 topics were related to public health concerns. These topics primarily scrutinized the safety of prepared dish production processes, raw materials, packaging materials, and additives. Moreover, significant public's interest was in the right to informed consumption across different contexts. Notably, the most pronounced public opposition emerged regarding introducing prepared dishes into primary and secondary school canteens, with criticisms directed at the negligence of educational authorities and the ethics of manufacturers. Additionally, there were strong recommendations for media organizations to play a more active role in monitoring public opinion and for government agencies to enhance regulatory oversight. Conclusion: The findings of this study indicate that more than half of the Chinese public maintain a negative perception towards prepared dishes, particularly concerning about health implications. Chinese individuals display considerable sensitivity and intense reactions to news and events related to prepared dishes. Consequently, the study recommends that manufacturers directly address public psychological perceptions, proactively enhance production processes and service quality, and increase transparency in public communications to improve corporate image and people acceptance of prepared dishes. Additionally, supervisory and regulatory efforts must be intensified by media organizations and governmental bodies, fostering the healthy development of the prepared food industry in China.

Anlotinib plus oral fluoropyrimidine S-1 in refractory or relapsed small-cell lung cancer (SALTER TRIAL): a multicenter, single-arm, phase II trial.

BACKGROUND: Patients with small-cell lung cancer (SCLC) have few treatment options and dismal overall survival (OS) after failed platinum-based chemotherapy. METHODS: The eligibility criteria of this phase II clinical trial included patients with measurable disease, age of 18 to 75 years, a confirmed diagnosis of disease progression or recurrence after prior platinum-based chemotherapy with a pathologically proven diagnosis of SCLC. Patients were treated with anlotinib at a dosage of 12 mg once daily (QD) and S-1 at 60 mg twice daily (BID) for 2 weeks, followed by a 1-week treatment-free interval. After six cycles of the above treatment, patients continued the maintenance therapy using S-1 monotherapy at 60 mg/ BID for 2 weeks, followed by a 1-week treatment-free interval until disease progression. RESULTS: From March 2019 to June 2020, a total of 71 patients were initially assessed for eligibility in this study. Out of these, 52 patients who met the inclusion criteria were enrolled, and 48 patients received at least two doses of the study drug. The median follow-up time was 25.1 months. The ORR was seen in 21 patients (43.8%). The median PFS was 4.5 months (95% CI, 3.5-5.5 months), and the median OS was 5.9 months (95% CI, 4.6-7.3 months). The most common grade 3-4 treatment-related adverse events were thrombocytopenia (16.7%), anemia (14.6%), neutropenia (14.6%), and hypertension (10.4%). No treatment-related death occurred. CONCLUSIONS: The combination of anlotinib with oral fluoropyrimidine S-1 demonstrated notable activity in relapsed or refractory SCLC, showing a favorable ORR and an acceptable, manageable safety profile. TRIAL REGISTRATION: This trial was registered with ClinicalTrial.gov (NCT03823118) on 3 January 2019.

Elucidating the genotoxicity of Fusobacterium nucleatum-secreted mutagens in colorectal cancer carcinogenesis.

BACKGROUND: Fusobacterium nucleatum (F. nucleatum) is one of the key tumorigenic bacteria in colorectal cancer (CRC), yet how F. nucleatum is involved in colorectal cancer carcinogenesis remains unknown. RESULTS: In the present study, we carried out PathSeq analysis on RNA sequencing data from the 430 primary colon adenocarcinomas in TCGA database to assess the relationship between patients' survival and F. nucleatum abundance. Among patients with cecum and ascending colon tumors, we found that F. nucleatum transcriptome abundance is positively correlated with mutation load. We further demonstrated that patients with both high tumoral abundance of F. nucleatum and high mutation load exhibited poorer survival and DNA damage. We furthermore determined that F. nucleatum-conditioned medium (Fn. CM) induces DNA damage in both in vitro and in vivo studies. In addition, two F. nucleatum-secreted mutagens, namely DL-homocystine and allantoic acid, were identified to lead to DNA damage. CONCLUSIONS: Our finding delineates the genotoxicity of F.nucleatum-secreted mutagens, which provides a basis for further work to investigate the role of F. nucleatum in the pathogenicity of CRC.

The Neuroprotective and Anxiolytic Effects of Magnesium Sulfate on Retinal Dopaminergic Neurons in 6-OHDA-Induced Parkinsonian Rats: A Pilot Study.

This study investigates the protective effects of magnesium sulfate on dopamine neurons in the retinas of rats with 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (PD). Rapidly progressing cognitive decline often precedes or coincides with the motor symptoms associated with PD. PD patients also frequently exhibit visual function abnormalities. However, the specific mechanisms underlying visual dysfunction in PD patients are not yet fully understood. Therefore, this study aims to investigate whether magnesium homeostasis affects dopaminergic neurons in the retina of PD rats. Thirty-six rats were divided into four groups: (1) control, (2) control with magnesium sulfate (control/MgSO4), (3) Parkinson's disease (PD), and (4) Parkinson's disease with magnesium sulfate (PD/MgSO4). The apomorphine-induced (APO) rotation test assessed the success of the PD models. The open-field experiment measured the rats' anxiety levels. Tyrosine hydroxylase (TH) and glutamate levels, indicators of dopamine neuron survival, were detected using immunofluorescence staining. Protein levels of solute carrier family 41 A1 (SCL41A1), magnesium transporter 1 (MagT1), and cyclin M2 (CNNM2) in the retina were analyzed using Western blot. Results showed that, compared to the PD group, rats in the PD/MgSO4 group had improved psychological states and motor performance at two and four weeks post-surgery. The PD/MgSO4 group also exhibited significantly higher TH fluorescence intensity in the left retinas and lower glutamate fluorescence intensity than the PD group. Additional experiments indicated that the protein levels of SLC41A1, MagT1, and CNNM2 were generally higher in the retinas of the PD/MgSO4 group, along with an increase in retinal magnesium ion content. This suggests that magnesium sulfate may reduce glutamate levels and protect dopamine neurons in the retina. Thus, magnesium sulfate might have therapeutic potential for visual functional impairments in PD patients.

Integrative proteomic and metabolomic elucidation of cardiomyopathy with in vivo and in vitro models and clinical samples.

Cardiomyopathy is a prevalent cardiovascular disease that affects individuals of all ages and can lead to life-threatening heart failure. Despite its variety in types, each with distinct characteristics and causes, our understanding of cardiomyopathy at a systematic biology level remains incomplete. Mass spectrometry-based techniques have emerged as powerful tools, providing a comprehensive view of the molecular landscape and aiding in the discovery of biomarkers and elucidation of mechanisms. This review highlights the significant potential of integrating proteomic and metabolomic approaches with specialized databases to identify biomarkers and therapeutic targets across different types of cardiomyopathies. In vivo and in vitro models, such as genetically modified mice, patient-derived or induced pluripotent stem cells, and organ chips, are invaluable in exploring the pathophysiological complexities of this disease. By integrating omics approaches with these sophisticated modeling systems, our comprehension of the molecular underpinnings of cardiomyopathy can be greatly enhanced, facilitating the development of diagnostic markers and therapeutic strategies. Among the promising therapeutic targets are those involved in extracellular matrix remodeling, sarcomere damage, and metabolic remodeling. These targets hold the potential to advance precision therapy in cardiomyopathy, offering hope for more effective treatments tailored to the specific molecular profiles of patients.

Clinical and pathogen features of COVID-19-associated infections during an Omicron strain outbreak in Guangzhou, China.

Although the Omicron variant has been associated with greater transmissibility and tropism of the upper respiratory tract, the clinical and pathogenic features of patients infected with the Omicron variant during an outbreak in China have been unclear. Adults with COVID-19 were retrospectively enrolled from seven medical centers in Guangzhou, China, and clinical information and specimens ( BALF, sputum, and throat swabs) from participants were collected. Conventional detection methods, metagenomics next-generation sequencing (mNGS), and other methods were used to detect pathogens in lower respiratory tract samples. From December 2022 to January 2023, we enrolled 836 patients with COVID-19, among which 56.7% patients had severe/critical illness. About 91.4% of patients were infected with the Omicron strain (BA.5.2). The detection rate of possible co-infection pathogens was 53.4% by mNGS, including Klebsiella pneumoniae (16.3%), Aspergillus fumigatus (12.2%), and Pseudomonas aeruginosa (11.8%). The co-infection rate was 19.5%, with common pathogens being Streptococcus pneumoniae (11.5%), Haemophilus influenzae (9.2%), and Adenovirus (6.9%). The superinfection rate was 75.4%, with common pathogens such as Klebsiella pneumoniae (26.1%) and Pseudomonas aeruginosa (19.4%). Klebsiella pneumoniae (27.1%% vs 6.1%, P < 0.001), Aspergillus fumigatus (19.6% vs 5.3%, P = 0.001), Acinetobacter baumannii (18.7% vs 4.4%, P = 0.001), Pseudomonas aeruginosa (16.8% vs 7.0%, P = 0.024), Staphylococcus aureus (14.0% vs 5.3%, P = 0.027), and Streptococcus pneumoniae (0.9% vs 10.5%, P = 0.002) were more common in severe cases. Co-infection and superinfection of bacteria and fungi are common in patients with severe pneumonia associated with Omicron variant infection. Sequencing methods may aid in the diagnosis and differential diagnosis of pathogens. IMPORTANCE: Our study has analyzed the clinical characteristics and pathogen spectrum of the lower respiratory tract associated with co-infection or superinfection in Guangzhou during the outbreak of the Omicron strain, particularly after the relaxation of the epidemic prevention and control strategy in China. This study will likely prompt further research into the specific issue, which will benefit clinical practice.

Study on the cross-resistance of Aedes albopictus (Skuse) (Diptera: Culicidae) to deltamethrin and pyriproxyfen.

BACKGROUND: Insecticide resistance poses a significant challenge in the implementation of vector-borne disease control strategies. We have assessed the resistance levels of Aedes albopictus to deltamethrin and pyriproxyfen (PPF) in Fujian Province (China) and investigated the correlation between these resistance levels and mutations in the voltage-gated sodium channel (VGSC). METHODS: The WHO bioassay protocol was used to evaluate the resistance coefficient of Ae. albopictus to deltamethrin and PPF, comparing a susceptible population from the Foshan (FS) area with wild populations from the Sanming (SM), Quanzhou (QZ), Zhangzhou (ZZ), Putian (PT) and Fuzhou (FZ) areas in Fujian Province. Genomic DNA was analyzed by PCR and sequencing to detect knockdown resistance (kdr) in the VGSC, specifically at the pyrethroid resistance alleles V1016V, I1532I and F1534F. Molecular docking was also performed to analyze the binding interactions of PPF and its metabolite 4'-OH-PPF to cytochrome P450 (CYP) 2C19, 2C9 and 3A4 and Ae. albopictus methoprene-tolerant receptors (AeMet), respectively. RESULTS: The analysis of resistance to deltamethrin and PPF among Ae. albopictus populations from the various regions revealed that except for the sensitive population in FS and the SM population, the remaining four regional populations demonstrated resistance levels ranging from 4.31- to 18.87-fold for deltamethrin and from 2.85- to 3.62-fold for PPF. Specifically, the FZ and PT populations exhibited high resistance to deltamethrin, whereas the ZZ and QZ populations approached moderate resistance levels. Also, the resistance of the FZ, PT and ZZ populations to PPF increased slowly but consistently with the increasing trend of deltamethrin resistance. Genomic analysis identified multiple non-synonymous mutations within the VGSC gene; the F1534S and F1534L mutations showed significant resistance to deltamethrin in Ae. albopictus. Molecular docking results revealed that PPF and its metabolite 4'-OH-PPF bind to the Ae. albopictus AeMet receptor and CYP2C19. CONCLUSIONS: The wild Ae. albopictus populations of Fujian Province showed varying degrees of resistance to deltamethrin and PPF and a trend of cross-resistance to deltamethrin and PPF. Increased vigilance is needed for potential higher levels of cross-resistance, especially in the PT and FZ regions.

Dynamic changes of anthocyanins during 'Ziyan' tea wine processing.

In this study, the dynamic changes of different anthocyanins in the processing of 'Ziyan' tea wine were investigated quantitatively. Results showed that six types of anthocyanins, namely petunidin, malvidin, pelargonidin, delphinidin, cyanidin and peonidin, as well as two co-pigmented substances, procyanidins and flavonoids, were detected in 'Ziyan' tea wine. As fermentation proceeded, the contents of petunidin, pelargonidin, delphinidin, cyanidin and peonidin decreased. Among them, petunidin, peonidin and pelargonidin showed a tendency of decreasing first, then increasing and finally decreasing, whereas delphinidin and cyanidin continued to decrease during fermentation. Variation trend of procyanidins and flavonoids was consistent with those of petunidin. Furthermore, metabolism of delphinidin, cyanidin and pelargonidin were main pathways responsible for the anthocyanin changes during 'Ziyan' tea wine processing. These findings suggested that the color of 'Ziyan' tea wine was achieved by the combination of various anthocyanins in different ratios and the co-pigmentation of procyanidins and flavonoids.

Metabolomics and proteomics reveal the inhibitory effect of Lactobacillus crispatus on cervical cancer.

Cervical cancer remains a significant global health issue due to its high morbidity and mortality rates. Recently, Lactobacillus crispatus has been recognized for its crucial role in maintaining cervical health. While some studies have explored the use of L. crispatus to mitigate cervical cancer, the underlying mechanisms remain largely unknown. In this study, we employed non-targeted proteomics and metabolomics to investigate how L. crispatus affects the growth of cervical cancer cells (SiHa) and normal cervical cells (Ect1/E6E7). Our findings indicated that the inhibitory effect of L. crispatus on SiHa cells was associated with various biological processes, notably the ferroptosis pathway. Specifically, L. crispatus was found to regulate the expression of proteins such as HMOX1, SLC39A14, VDAC2, ACSL4, and LPCAT3 by SiHa cells, which are closely related to ferroptosis. Additionally, it activated the tricarboxylic acid (TCA) cycle in SiHa cells, leading to increased levels of reactive oxygen species (ROS) and lipid peroxides (LPO). These results revealed the therapeutic potential of L. crispatus in targeting the ferroptosis pathway for cervical cancer treatment, opening new avenues for research and therapy in cervical cancer.

Unconventional insulator-to-metal phase transition in Mn3Si2Te6.

The nodal-line semiconductor Mn3Si2Te6 is generating enormous excitment due to the recent discovery of a field-driven insulator-to-metal transition and associated colossal magnetoresistance as well as evidence for a new type of quantum state involving chiral orbital currents. Strikingly, these qualities persist even in the absence of traditional Jahn-Teller distortions and double-exchange mechanisms, raising questions about exactly how and why magnetoresistance occurs along with conjecture as to the likely signatures of loop currents. Here, we measured the infrared response of Mn3Si2Te6 across the magnetic ordering and field-induced insulator-to-metal transitions in order to explore colossal magnetoresistance in the absence of Jahn-Teller and double-exchange interactions. Rather than a traditional metal with screened phonons, the field-driven insulator-to-metal transition leads to a weakly metallic state with localized carriers. Our spectral data are fit by a percolation model, providing evidence for electronic inhomogeneity and phase separation. Modeling also reveals a frequency-dependent threshold field for carriers contributing to colossal magnetoresistance which we discuss in terms of polaron formation, chiral orbital currents, and short-range spin fluctuations. These findings enhance the understanding of insulator-to-metal transitions in new settings and open the door to the design of unconventional colossal magnetoresistant materials.

In Vitro and In Vivo Assessments of Newly Isolated N4-like Bacteriophage against ST45 K62 Capsular-Type Carbapenem-Resistant Klebsiella pneumoniae: vB_kpnP_KPYAP-1.

The rise of carbapenem-resistant Klebsiella pneumoniae (CRKP) presents a significant global challenge in clinical and healthcare settings, severely limiting treatment options. This study aimed to utilize a bacteriophage as an alternative therapy against carbapenem-resistant K. pneumoniae. A novel lytic N4-like Klebsiella phage, vB_kpnP_KPYAP-1 (KPYAP-1), was isolated from sewage. It demonstrated efficacy against the K62 serotype polysaccharide capsule of blaOXA-48-producing K. pneumoniae. KPYAP-1 forms small, clear plaques, has a latent period of 20 min, and reaches a growth plateau at 35 min, with a burst size of 473 plaque-forming units (PFUs) per infected cell. Phylogenetic analysis places KPYAP-1 in the Schitoviridae family, Enquatrovirinae subfamily, and Kaypoctavirus genus. KPYAP-1 employs an N4-like direct terminal repeat mechanism for genome packaging and encodes a large virion-encapsulated RNA polymerase. It lacks integrase or repressor genes, antibiotic resistance genes, bacterial virulence factors, and toxins, ensuring its safety for therapeutic use. Comparative genome analysis revealed that the KPYAP-1 genome is most similar to the KP8 genome, yet differs in tail fiber protein, indicating variations in host recognition. In a zebrafish infection model, KPYAP-1 significantly improved the survival rate of infected fish by 92% at a multiplicity of infection (MOI) of 10, demonstrating its potential for in vivo treatment. These results highlight KPYAP-1 as a promising candidate for developing phage-based therapies targeting carbapenemase-producing K. pneumoniae.

Correlation and Clinical Significance of HBD-2 and CXCL-1/2 Levels at Skin Lesions with Psoriasis Vulgaris Severity.

OBJECTIVE: This study was performed to explore the clinical significance of the expression of human beta-defensin 2 (HBD-2) and chemokine ligand 1/2 (CXCL-1/2) in psoriasis vulgaris. METHODS: This study retrospectively included the study group (n = 160) and control group (n = 100) for analysis. The levels of inflammatory indicators, blood biochemical indicators, and immune indicators using ELISA. The psoriasis area and severity index (PASI) was used to evaluate disease severity. Levels of HBD-2, CXCL-1, CXCL-2 and CCL20 were determined by RT-PCR. The correlations of HBD-2, CXCL-1 and CXCL-2 levels with CCL20 and PASI scores were analyzed. The diagnostic value of HBD-2, CXCL-1 and CXCL-2 in psoriasis vulgaris was analyzed by ROC curve. RESULTS: HBD-2, CXCL-1 and CXCL-2 were highly expressed in the lesions of psoriasis vulgaris patients, and were positively correlated with CCL20 and PASI score. HBD-2, CXCL-1 and CXCL-2 alone or in combination had high diagnostic value for psoriasis vulgaris and severe psoriasis, and the combined diagnostic value of the three was higher than that of a single indicator. CONCLUSION: HBD-2, CXCL-1, and CXCL-2 levels are closely related to the severity of psoriasis vulgaris and can effectively diagnose the occurrence and progression of psoriasis vulgaris.

Magnesium Ion: A New Switch in Tumor Treatment.

The magnesium ion is an essential cation in the human body and participates in numerous physiological activities. A deficiency in magnesium ions is closely associated with tumor development, and supplementation with magnesium ions has been shown to partially inhibit tumor growth. However, the specific mechanisms by which magnesium ions suppress tumor proliferation remain unclear. Currently, studies have revealed that mitochondria may serve as a crucial intermediate link in the regulation of tumors by magnesium ions. Mitochondria might intervene in the proliferation and invasion of tumor cells by modulating energy metabolism and oxidative stress levels. Regrettably, there has been no comprehensive review of the role of magnesium in cancer therapy to date. Therefore, this article provides a comprehensive scrutiny of the relationship between magnesium ions and tumors, aiming to offer insights for clinical tumor treatment strategies involving magnesium ion intervention.

Multi-omics analysis identified extracellular vesicles as biomarkers for cardiovascular diseases.

Cell-derived extracellular vesicles (EVs) have emerged as a promising non-invasive liquid biopsy technique due to their accessibility and their ability to encapsulate and transport diverse biomolecules. EVs have garnered substantial research interest, notably in cardiovascular diseases (CVDs), where their roles in pathophysiology and as diagnostic and prognostic biomarkers are increasingly recognized. This review provides a comprehensive overview of EVs, starting with their origins, followed by the techniques used for their isolation and characterization. We explore the diverse cargo of EVs, including nucleic acids, proteins, lipids, and metabolites, highlighting their roles in intercellular communication and as potential biomarkers. We then delve into the application of genomics, transcriptomics, proteomics, and metabolomics in the analysis of EVs, particularly within the context of CVDs. Finally, we discuss how integrated multi-omics approaches are unveiling novel biomarkers, offering fresh insights into the diagnosis and prognosis of CVDs. This review underscores the growing importance of EVs in clinical diagnostics and the potential of multi-omics to propel future advancements in CVD biomarker discovery.

Efficacy and safety of extracorporeal shock wave therapy for upper limb tendonitis: a systematic review and meta-analysis of randomized controlled trials.

Objective: This study synthesized the highest level of evidence to analyse the effectiveness and safety of using extracorporeal shock wave therapy (ESWT) to treat upper limb tendonitis, which was unknown. Design: We conducted a systematic review and meta-analysis of 18 randomized controlled trials (RCTs) in PubMed, Embase, Web of Science, Medline, and the Cochrane Library. Methods: Two researchers performed the screening, data extraction, literature quality assessment, and heterogeneity analysis of the searched RCTs. Results: The main types of morbidity included rotator cuff tendonitis, lateral epicondylitis, finger tendonitis, and long bicipital tendonitis. The results of the meta-analysis showed that ESWT was effective in relieving pain in all four types of tendonitis. In addition, ESWT was more effective in relieving pain in patients with upper limb tendonitis than placebo at the 3- and 6-month follow-ups, especially with radial ESWT (RESWT). Data analysis of the forest plot showed that the experimental group with ESWT as an intervention had a significant improvement in function in patients with rotator cuff tendonitis at the 3-month follow-up. However, subgroup analysis showed that low-energy ESWT was effective in improving function in patients with calcified and non-calcified rotator cuff tendonitis, whereas it was not effective in relieving pain. Conclusion: ESWT can effectively improve the functional activity in patients with rotator cuff tendonitis and may produce positive analgesic effects in patients with upper limb tendonitis. The incidence of adverse effects is low. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023403594, identifier: PROSPERO, CRD42023403594.