Circular RNAs in human diseases.

Circular RNAs (circRNAs) are a unique class of RNA molecules formed through back-splicing rather than linear splicing. As an emerging field in molecular biology, circRNAs have garnered significant attention due to their distinct structure and potential functional implications. A comprehensive understanding of circRNAs' functions and potential clinical applications remains elusive despite accumulating evidence of their involvement in disease pathogenesis. Recent research highlights their significant roles in various human diseases, but comprehensive reviews on their functions and applications remain scarce. This review provides an in-depth examination of circRNAs, focusing first on their involvement in non-neoplastic diseases such as respiratory, endocrine, metabolic, musculoskeletal, cardiovascular, and renal disorders. We then explore their roles in tumors, with particular emphasis on exosomal circular RNAs, which are crucial for cancer initiation, progression, and resistance to treatment. By detailing their biogenesis, functions, and impact on disease mechanisms, this review underscores the potential of circRNAs as diagnostic biomarkers and therapeutic targets. The review not only enhances our understanding of circRNAs' roles in specific diseases and tumor types but also highlights their potential as novel diagnostic and therapeutic tools, thereby paving the way for future clinical investigations and potential therapeutic interventions.

Exploration of the causal relationship between inflammatory cytokines and prostate carcinoma: a comprehensive Mendelian randomization study.

Background: Prostate cancer (PCa) is one of the most prevalent malignancies affecting males; however, the role of inflammatory activity in the pathogenesis of this disease is not yet fully elucidated. Although inflammation is recognized as being closely associated with the onset and progression of PCa, the specific causal relationships between individual inflammatory factors and the disease require further clarification. Methods: Mendelian randomization (MR) methodologies can mitigate bias by utilizing whole-genome sequencing data, leveraging specific genetic variants to assess causal relationships between a given exposure and an outcome of interest. This research employed an MR approach to investigate the association between inflammatory cytokines and PCa. Results: In total, 44 inflammatory cytokines were evaluated in a large GWAS dataset to enable the drawing of robust conclusions. Elevated circulating C-reactive protein (CRP) and prostaglandin E2 (PGE-2) levels were related to greater PCa risk. The reverse Mendelian randomization (MR) study indicates a causal relationship between prostate cancer and stem cell factor (SCF) (P=0.025). Conclusion: CRP and PGE-2 play crucial roles in the regulation of PCa development. Moreover, PCa may have an impact on SCF levels. Further research is imperative to elucidate whether these biomarkers can be effectively utilized to prevent or treat PCa.

Impact Assessment of the "4+1 Nursing Operation Mode" on Enhancing the Efficacy of Alveolar Surgery Diagnosis and Treatment.

OBJECTIVE: The aim of this study is to evaluate the impact of the "4+1 Nursing Operation Mode" on improving the efficacy of alveolar surgery and the effectiveness of nursing. METHODS: A total of 200 patients were recruited from the oral and maxillofacial surgery outpatient department at the School and Hospital of Stomatology, Wuhan University, between November and December 2023. These patients were allocated into 2 groups: a control group and an experimental group. The treatment for these groups involved different combinations of physicians and nurses, including doctors A and B, and nurses A, B, and C. In November 2023, doctor A treated 50 patients with the assistance of nurses A and C under the "4+1 Nursing Operation Mode," while another 50 patients were treated by doctor A with the assistance of nurse A following the "Four-Handed Operation Mode." In December 2023, doctor B treated 50 patients with the assistance of nurse B under the "Four-Handed Operation Mode," and another 50 patients were treated by doctor B with the assistance of nurses B and C using the "4+1 Nursing Operation Mode." Patient visit durations were documented, and patient satisfaction with diagnostic and treatment services was evaluated via a questionnaire survey. RESULTS: In comparison to the "Four-Handed Operation Mode," the "4+1 Nursing Operation Mode" resulted in a 27% reduction in patient visit times and an improvement in patient satisfaction with nursing services. CONCLUSIONS: The "4+1 Nursing Operation Mode" surpasses the "Four-Handed Operation Mode" in terms of efficiency. It not only reduces patient visit times and enhances doctor work efficiency but also improves patient satisfaction with nursing services.

Folate, Homocysteine, and Adverse Outcomes After Ischemic Stroke.

BACKGROUND: As a risk factor of cardiovascular diseases, homocysteine can be effectively lowered by folate. However, the associations of folate and homocysteine levels with the prognosis of ischemic stroke remained unclear. METHODS AND RESULTS: A total of 3530 patients with ischemic stroke were included. Serum folate and homocysteine levels were measured at admission. The primary outcome was composite of death and major disability (modified Rankin Scale score≥3) at 3 months after stroke onset. Univariate and multivariate logistic regression models were used. The mediation effect of homocysteine was examined. During follow-up, 1056 participants developed the primary outcome. In the univariate model, participants in the highest quartile of folate had a 29% (95% CI, 0.58-0.87) decreased risk of primary outcome compared with those in the lowest quartile. After multivariate adjustment, the odds ratio associated with the highest quartile of folate was 0.58 (95% CI, 0.46-0.73) for primary outcome. In contrast, participants in the highest quartile of homocysteine had a 52% (95% CI, 1.24-1.98) increased risk of primary outcome compared with those in the lowest quartile. After multivariate adjustment, the odds ratio associated with highest quartile of homocysteine was 1.57 (95% CI, 1.24-1.98) for primary outcome. In addition, 25.5% of the observed associations between folate and primary outcome was mediated through homocysteine (P=0.012). CONCLUSIONS: High folate levels were associated with low risks of death and major disability among Chinese patients with ischemic stroke, and homocysteine partially mediated the observed potential beneficial role of folate.

The potential of a nomogram risk assessment model for the diagnosis of abdominal aortic aneurysm: a multicenter retrospective study.

The incidence of abdominal aortic aneurysm (AAA) is very high, but there is no risk assessment model for early identification of AAA in clinic. The aim of this study was to develop a nomogram risk assessment model for predicting AAA. The data of 280 patients diagnosed as AAA and 385 controls in The Affiliated Suzhou Hospital of Nanjing Medical University were retrospectively reviewed. The LASSO regression method was applied to filter variables, and multivariate logistic regression was used to construct a nomogram. The discriminatory ability of the model was determined by calculating the area under the curve (AUC). The calibration capability of the model is evaluated by using bootstrap (resampling = 1000) internal validation and Hosmer-Lemeshow test. The clinical utility and clinical application value were evaluated by decision curve analysis (DCA) and clinical impact curve (CIC). In addition, a retrospective review of 133 AAA patients and 262 controls from The First Affiliated Hospital of Soochow University was performed as an external validation cohort. Eight variables are selected to construct the nomogram of AAA risk assessment model. The nomogram predicted AAA with AUC values of 0.928 (95%CI, 0.907-0.950) in the training cohort, and 0.902 (95%CI, 0.865-0.940) in the external validation cohort, the risk prediction model has excellent discriminative ability. The calibration curve and Hosmer-Lemeshow test proved that the nomogram predicted outcomes were close to the ideal curve, the predicted outcomes were consistent with the real outcomes, the DCA curve and CIC curve showed that patients could benefit. This finding was also confirmed in the external validation cohort. In this study, a nomogram was constructed that incorporated eight demographic and clinical characteristics of AAA patients, which can be used as a practical approach for the personalized early screening and auxiliary diagnosis of the potential risk factors.

Learning From Human Attention for Attribute-Assisted Visual Recognition.

With prior knowledge of seen objects, humans have a remarkable ability to recognize novel objects using shared and distinct local attributes. This is significant for the challenging tasks of zero-shot learning (ZSL) and fine-grained visual classification (FGVC), where the discriminative attributes of objects have played an important role. Inspired by human visual attention, neural networks have widely exploited the attention mechanism to learn the locally discriminative attributes for challenging tasks. Though greatly promoted the development of these fields, existing works mainly focus on learning the region embeddings of different attribute features and neglect the importance of discriminative attribute localization. It is also unclear whether the learned attention truly matches the real human attention. To tackle this problem, this paper proposes to employ real human gaze data for visual recognition networks to learn from human attention. Specifically, we design a unified Attribute Attention Network (A 2 Net) that learns from human attention for both ZSL and FGVC tasks. The overall model consists of an attribute attention branch and a baseline classification network. On top of the image feature maps provided by the baseline classification network, the attribute attention branch employs attribute prototypes to produce attribute attention maps and attribute features. The attribute attention maps are converted to gaze-like attentions to be aligned with real human gaze attention. To guarantee the effectiveness of attribute feature learning, we further align the extracted attribute features with attribute-defined class embeddings. To facilitate learning from human gaze attention for the visual recognition problems, we design a bird classification game to collect real human gaze data using the CUB dataset via an eye-tracker device. Experiments on ZSL and FGVC tasks without/with real human gaze data validate the benefits and accuracy of our proposed model. This work supports the promising benefits of collecting human gaze datasets and automatic gaze estimation algorithms learning from human attention for high-level computer vision tasks.

Soil keystone viruses are regulators of ecosystem multifunctionality.

Ecosystem multifunctionality reflects the capacity of ecosystems to simultaneously maintain multiple functions which are essential bases for human sustainable development. Whereas viruses are a major component of the soil microbiome that drive ecosystem functions across biomes, the relationships between soil viral diversity and ecosystem multifunctionality remain under-studied. To address this critical knowledge gap, we employed a combination of amplicon and metagenomic sequencing to assess prokaryotic, fungal and viral diversity, and to link viruses to putative hosts. We described the features of viruses and their potential hosts in 154 soil samples from 29 farmlands and 25 forests distributed across China. Although 4,460 and 5,207 viral populations (vOTUs) were found in the farmlands and forests respectively, the diversity of specific vOTUs rather than overall soil viral diversity was positively correlated with ecosystem multifunctionality in both ecosystem types. Furthermore, the diversity of these keystone vOTUs, despite being 10-100 times lower than prokaryotic or fungal diversity, was a better predictor of ecosystem multifunctionality and more strongly associated with the relative abundances of prokaryotic genes related to soil nutrient cycling. Gemmatimonadota and Actinobacteria dominated the host community of soil keystone viruses in the farmlands and forests respectively, but were either absent or showed a significantly lower relative abundance in that of soil non-keystone viruses. These findings provide novel insights into the regulators of ecosystem multifunctionality and have important implications for the management of ecosystem functioning.

[Behavioral treatment of functional anejaculation and factors influencing the therapeutic effect].

OBJECTIVE: To study the effect of a modified behavioral treatment (MBT) on functional anejaculation and analyze the factors influencing the therapeutic efficacy. METHODS: We enrolled in this study 59 men aged 24－45 years visiting the Andrology Clinic of Shanghai First Maternity and Infant Hospital from August 2019 to May 2021 and complaining of aejaculation in sexual intercourse but normally ejaculating during masturbation. Thirty-nine of the patients underwent conventional behavioral treatment (the CBT group) and the other 20 received MBT, namely, changing the masturbation method combined with audiovisual stimulation during sexual intercourse (the MBT group). We compared the therapeutic effects between the two groups of patients, and analyzed the correlation of the outcomes of MBT with age, abstinence duration, use of audiovisual stimulation, change of the sexual position, mean bilateral testis volume and sex hormone levels. RESULTS: After treatment, 22 (37.29%) of the patients achieved successful ejaculation at least once in sexual intercourse, 11 (55.00%) in the MBT group, and the other 11 (28.21) in the CBT group, with a significantly higher effectiveness rate in the former than in the latter (P<0.05). The effectiveness rate was significantly correlated to the method of standing-position masturbation plus sexual intercourse and reduction in the frequency of masturbation among various strategies of behavioral treatment (P<0.05). CONCLUSION: MBT has a certain effect on functional anejaculation, and targeting the previous events of the patient is the key to the therapeutic efficacy. Further exploration of more effective strategies of behavioral treatment will become the trend of development in the management of functional anejaculation.

The additive effect of the triglyceride-glucose index and estimated glucose disposal rate on long-term mortality among individuals with and without diabetes: a population-based study.

BACKGROUND: The triglyceride-glucose (TyG) index and estimated glucose disposal rate (eGDR), which are calculated using different parameters, are widely used as markers of insulin resistance and are associated with cardiovascular diseases and prognosis. However, whether they have an additive effect on the risk of mortality remains unclear. This study aimed to explore whether the combined assessment of the TyG index and eGDR improved the prediction of long-term mortality in individuals with and without diabetes. METHODS: In this cross-sectional and cohort study, data were derived from the National Health and Nutrition Examination Survey (NHANES) 2001-2018, and death record information was obtained from the National Death Index. The associations of the TyG index and eGDR with all-cause and cardiovascular mortality were determined by multivariate Cox regression analysis and restricted cubic splines. RESULTS: Among the 17,787 individuals included in the analysis, there were 1946 (10.9%) all-cause deaths and 649 (3.6%) cardiovascular deaths during a median follow-up of 8.92 years. In individuals with diabetes, the restricted cubic spline curves for the associations of the TyG index and eGDR with mortality followed a J-shape and an L-shape, respectively. The risk of mortality significantly increased after the TyG index was > 9.04 (all-cause mortality) or > 9.30 (cardiovascular mortality), and after eGDR was < 4 mg/kg/min (both all-cause and cardiovascular mortality). In individuals without diabetes, the association between eGDR and mortality followed a negative linear relationship. However, there was no association between the TyG index and mortality. Compared with individuals in the low TyG and high eGDR group, those in the high TyG and low eGDR group (TyG > 9.04 and eGDR < 4) showed the highest risk for all-cause mortality (hazard ratio [HR] = 1.592, 95% confidence interval [CI] 1.284-1.975) and cardiovascular mortality (HR = 1.683, 95% CI 1.179-2.400) in the overall population. Similar results were observed in individuals with and without diabetes. CONCLUSIONS: There was a potential additive effect of the TyG index and eGDR on the risk of long-term mortality in individuals with and without diabetes, which provided additional information for prognostic prediction and contributed to improving risk stratification.

Mesoporous zinc-polyphenol nanozyme for attenuating renal ischemia-reperfusion injury.

Aim: To target the reactive oxygen species (ROS) accumulation and renal tubular epithelial cell (rTEC) death in renal ischemia-reperfusion injury (IRI), we constructed a nanoparticle that offers ROS scavenging and rTEC-death inhibition: mesoporous zinc-tannic acid nanozyme (ZnTA). Materials & methods: After successfully constructing ZnTA, we proceeded to examine its effect on ROS accumulation, cellular ferroptosis and apoptosis, as well as injury severity. Results: Malondialdehyde, Fe2+ amounts and 4-HNE staining demonstrated that ZnTA effectively attenuated rTEC ferroptosis. TUNEL staining confirmed that Zn2+ carried by ZnTA could effectively inhibit caspase 3 and caspase 9, mitigating apoptosis. Finally, it reduced renal IRI through the synergistic effect of ROS scavenging and cell-death inhibition. Conclusion: This study is expected to provide a paradigm for a combined therapeutic strategy for renal IRI.

[Box: see text].

Epidemiological features and temporal trends of the co-infection between HIV and tuberculosis, 1990-2021: findings from the Global Burden of Disease Study 2021.

BACKGROUND: The co-infection of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and tuberculosis (TB) poses a significant clinical challenge and is a major global public health issue. This study aims to elucidate the disease burden of HIV-TB co-infection in global, regions and countries, providing critical information for policy decisions to curb the HIV-TB epidemic. METHODS: The ecological time-series study used data from the Global Burden of Disease (GBD) Study 2021. The data encompass the numbers of incidence, prevalence, mortality, and disability-adjusted life year (DALY), as well as age-standardized incidence rate (ASIR), prevalence rate (ASPR), mortality rate (ASMR), and DALY rate for HIV-infected drug-susceptible tuberculosis (HIV-DS-TB), HIV-infected multidrug-resistant tuberculosis (HIV-MDR-TB), and HIV-infected extensively drug-resistant tuberculosis (HIV-XDR-TB) from 1990 to 2021. from 1990 to 2021. The estimated annual percentage change (EAPC) of rates, with 95% confidence intervals (CIs), was calculated. RESULTS: In 2021, the global ASIR for HIV-DS-TB was 11.59 per 100,000 population (95% UI: 0.37-13.05 per 100,000 population), 0.55 per 100,000 population (95% UI: 0.38-0.81 per 100,000 population), for HIV-MDR-TB, and 0.02 per 100,000 population (95% UI: 0.01-0.03 per 100,000 population) for HIV-XDR-TB. The EAPC for the ASIR of HIV-MDR-TB and HIV-XDR-TB from 1990 to 2021 were 4.71 (95% CI: 1.92-7.59) and 13.63 (95% CI: 9.44-18.01), respectively. The global ASMR for HIV-DS-TB was 2.22 per 100,000 population (95% UI: 1.73-2.74 per 100,000 population), 0.21 per 100,000 population (95% UI: 0.09-0.39 per 100,000 population) for HIV-MDR-TB, and 0.01 per 100,000 population (95% UI: 0.00-0.03 per 100,000 population) for HIV-XDR-TB in 2021. The EAPC for the ASMR of HIV-MDR-TB and HIV-XDR-TB from 1990 to 2021 were 4.78 (95% CI: 1.32-8.32) and 10.00 (95% CI: 6.09-14.05), respectively. CONCLUSIONS: The findings indicate that enhancing diagnostic and treatment strategies, strengthening healthcare infrastructure, increasing access to quality medical care, and improving public health education are essential to combat HIV-TB co-infection.

Infection and biogeographical characteristics of Paragonimus westermani and P. skrjabini in humans and animal hosts in China: A systematic review and meta-analysis.

BACKGROUND: Paragonimiasis, primarily caused by Paragonimus westermani and P. skrjabini in China, is a common food-borne parasitic zoonosis. However, the national distribution of Paragonimus spp. infection and its associated environmental determinants remain poorly understood. In this paper, we summarize the infection of P. westermani and P. skrjabini and describe key biogeographical characteristics of the endemic areas in China. METHODS: Data on Paragonimus infection in humans and animal hosts were extracted from eight electronic databases, including CNKI, CWFD, Chongqing VIP, SinoMed, Medline, Embase, PubMed, and Web of Science. A random-effects meta-analysis model was used to estimate the pooled prevalence. All survey locations were georeferenced and plotted on China map, and scatter plots were used to illustrate the biogeographical characteristics of regions reporting Paragonimus infection. RESULTS: A total of 28,948 cases of human paragonimiasis have been documented, with 2,401 cases reported after 2010. Among the 11,443 cases with reported ages, 88.05% were children or adolescents. The pooled prevalence of P. skrjabini is 0.45% (95% CI: 0.27-0.66%) in snails, 31.10% (95% CI: 24.77-37.80%) in the second intermediate host, and 20.31% (95% CI: 9.69-33.38%) in animal reservoirs. For P. westermani, the pooled prevalence is 0.06% (95% CI: 0.01-0.13%) in snails, 52.07% (95% CI: 43.56-60.52%) in the second intermediate host, and 21.40% (95% CI: 7.82-38.99%) in animal reservoirs. Paragonimus are primarily distributed in regions with low altitude, high temperature, and high precipitation. In northeastern China, only P. westermani infections have been documented, while in more southern areas, infections of both P. westermani and P. skrjabini have been reported. CONCLUSIONS: Paragonimiasis remains prevalent in China, particularly among children and adolescents. Variations exist in the intermediate hosts and geographical distribution of P. westermani and P. skrjabini. Additionally, altitude, temperature, and precipitation may influence the distribution of Paragonimus.

A triangular-trapezoidal dual-channel shaping algorithm for resistive anode readout systems and its FPGA implementation.

This paper introduces a novel digital triangular-trapezoidal double-channel shaping algorithm to enhance the counting rate of resistive anode detectors. The algorithm is based on the trapezoidal shaping algorithm and improves it. At the extreme counting rate, the trapezoidal shaping algorithm cannot alleviate the pulse pileup, so the counting rate cannot meet the requirements of a high performance detector. The triangular-trapezoidal double-channel shaping algorithm is introduced in the resistance anode detector, which can replace the trapezoidal shaping filtering algorithm to process the output signal of the resistance anode detector and obtain the single photon position information. This improvement improves the counting rate of the resistor anode detector and reduces the resolution degradation caused by pulse pileup. The algorithm is simulated by System Generator software and implemented on FPGA (field programmable gate array). The triangular-trapezoidal double-channel shaping algorithm presented in this paper plays an important role in reducing electronic noise and pulse pileup. The algorithm is subjected to simulation testing, and it can recognize signals with a minimum pulse interval of 1 µs and counting rate up to 1000 kcps.

S100a8/a9 regulated by LPS/TLR4 axis plays an important role in Salmonella-based tumor therapy and host defense.

Bacteria are ideal anticancer agents and carriers due to their unique capabilities that are convenient in genetic manipulation, tumor-specific targeting, and deep-tissue penetration. However, the specific molecular mechanisms of bacteria-mediated cancer therapy (BMCT) have not been clarified. In this study, we found that TLR4 signaling pathway is critical for Salmonella-mediated tumor targeting, tumor suppression, and liver and spleen protection. TLR4 knockout in mice decreased the levels of cytokines and chemokines, such as S100a8, S100a9, TNF-α, and IL-1ß, in tumor microenvironments (TMEs) after Salmonella treatment, which inhibited tumor cell death and nutrient release, led to reduced bacterial contents in tumors and attenuated antitumor efficacy in a negative feedback manner. Importantly, we found that S100a8 and S100a9 played a leading role in Salmonella-mediated cancer therapy (SMCT). The antitumor efficacy was abrogated and liver damage was prominent when blocked with a specific inhibitor. These findings elucidated the mechanism of Salmonella-mediated tumor targeting, suppression, and host antibacterial defense, providing insights into clinical cancer therapeutics.

Reactive Oxygen Species-Scavenging Mesoporous Poly(tannic acid) Nanospheres Alleviate Acute Kidney Injury by Inhibiting Ferroptosis.

Acute kidney injury (AKI), predominantly associated with the excess production of endogenous ROS, is a serious renal dysfunction syndrome. Ferroptosis characterized by iron-dependent regulated cell death has significant involvement in AKI pathogenesis. As symptomatic treatment of AKI remains clinically limited, a new class of effective therapies has emerged, which is referred to as nanozyme. In our research, a natural mesoporous poly(tannic acid) nanosphere (referred to as PTA) was developed that can successfully mimic the activity of superoxide dismutase (SOD) by Mussel-inspired interface deposition strategy, for effective ROS scavenging and thus inhibition of ferroptosis to attenuate AKI. As anticipated, PTA mitigated oxidative stress and inhibited ferroptosis, as opposed to other modes of cell death such as pyroptosis or necrosis. Furthermore, PTA exhibited favorable biocompatibility and safeguarded the kidney against ferroptosis by enhancing the expression of SLC7a11/glutathione peroxidase 4(GPX4) and Nrf2/HO-1, while reducing the levels of ACSL4 protein in the ischemia and reperfusion injury (IRI)-induced AKI model. Moreover, PTA effectively suppressed aberrant expression of inflammatory factors. Overall, this study introduced antioxidative nanozymes in the form of mesoporous polyphenol nanospheres, showcasing exceptional therapeutic efficacy in addressing ROS-related diseases. This novel approach holds promise for clinical AKI treatment and broadens the scope of biomedical applications for nanozymes.

Associations between brain imaging-derived phenotypes and cognitive functions.

We aimed to evaluate the potential causal relationship between brain imaging-derived phenotypes and cognitive functions via Mendelian randomization analyses. Genetic instruments for 470 brain imaging-derived phenotypes were selected from a genome-wide association study based on the UK Biobank (n = 33,224). Statistics for cognitive functions were obtained from the genome-wide association study based on the UK Biobank. We used the inverse variance weighted Mendelian randomization method to investigate the associations between brain imaging-derived phenotypes and cognitive functions, and reverse Mendelian randomization analyses were performed for significant brain imaging-derived phenotypes to examine the reverse causation for the identified associations. We identified three brain imaging-derived phenotypes to be associated with verbal-numerical reasoning, including cortical surface area of the left fusiform gyrus (beta, 0.18 [95% confidence interval, 0.11 to 0.25], P = 4.74 × 10-7), cortical surface area of the right superior temporal gyrus (beta, 0.25 [95% confidence interval, 0.15 to 0.35], P = 6.30 × 10-7), and orientation dispersion in the left superior longitudinal fasciculus (beta, 0.14 [95% confidence interval, 0.09 to 0.20], P = 8.37 × 10-7). The reverse Mendelian randomization analysis indicated that verbal-numerical reasoning had no effect on these three brain imaging-derived phenotypes. This Mendelian randomization study identified cortical surface area of the left fusiform gyrus, cortical surface area of the right superior temporal gyrus, and orientation dispersion in the left superior longitudinal fasciculus as predictors of verbal-numerical reasoning.

Path to bacteriotherapy: From bacterial engineering to therapeutic perspectives.

The major reason for the failure of conventional therapies is the heterogeneity and complexity of tumor microenvironments (TMEs). Many malignant tumors reprogram their surface antigens to evade the immune surveillance, leading to reduced antigen-presenting cells and hindered T-cell activation. Bacteria-mediated cancer immunotherapy has been extensively investigated in recent years. Scientists have ingeniously modified bacteria using synthetic biology and nanotechnology to enhance their biosafety with high tumor specificity, resulting in robust anticancer immune responses. To enhance the antitumor efficacy, therapeutic proteins, cytokines, nanoparticles, and chemotherapeutic drugs have been efficiently delivered using engineered bacteria. This review provides a comprehensive understanding of oncolytic bacterial therapies, covering bacterial design and the intricate interactions within TMEs. Additionally, it offers an in-depth comparison of the current techniques used for bacterial modification, both internally and externally, to maximize their therapeutic effectiveness. Finally, we outlined the challenges and opportunities ahead in the clinical application of oncolytic bacterial therapies.

Synergistic integration of climate change and zoonotic diseases by artificial intelligence: a holistic approach for sustainable solutions.

Artificial intelligence (AI) is a rapidly evolving field that can impel research in communicable diseases with respect to climate projections, ecological indicators and environmental impact, at the same time revealing new, previously overlooked events. A number of zoonotic and vector-borne diseases already show signs of expanding their northern geographical ranges and appropriate risk assessment and decision support are urgently needed. The deployment of AI-enabled monitoring systems tracking animal populations and environmental changes is of immense potential in the study of transmission under different climate scenarios. In addition, AI's capability to identify new treatments should not only accelerate drug and vaccine discovery but also help predicting their effectiveness, while its contribution to genetic pathogen speciation would assist the evaluation of spillover risks with regard to viral infections from animals to human. Close collaboration between AI experts, epidemiologists and other stakeholders is not only crucial for responding to challenges interconnected with a variety of variables effectively, but also necessary to warrant responsible AI use. Despite its wider successful implementation in many fields, AI should be seen as a complement to, rather than a replacement of, traditional public health measures.

Schistosomiasis transmission in Zimbabwe: Modelling based on machine learning.

Zimbabwe, located in Southern Africa, faces a significant public health challenge due to schistosomiasis. We investigated this issue with emphasis on risk prediction of schistosomiasis for the entire population. To this end, we reviewed available data on schistosomiasis in Zimbabwe from a literature search covering the 1980-2022 period considering the potential impact of 26 environmental and socioeconomic variables obtained from public sources. We studied the population requiring praziquantel with regard to whether or not mass drug administration (MDA) had been regularly applied. Three machine-learning algorithms were tested for their ability to predict the prevalence of schistosomiasis in Zimbabwe based on the mean absolute error (MAE), the root mean squared error (RMSE) and the coefficient of determination (R2). The findings revealed different roles of the 26 factors with respect to transmission and there were particular variations between Schistosoma haematobium and S. mansoni infections. We found that the top-five correlation factors, such as the past (rather than current) time, unsettled MDA implementation, constrained economy, high rainfall during the warmest season, and high annual precipitation were closely associated with higher S. haematobium prevalence, while lower elevation, high rainfall during the warmest season, steeper slope, past (rather than current) time, and higher minimum temperature in the coldest month were rather related to higher S. mansoni prevalence. The random forest (RF) algorithm was considered as the formal best model construction method, with MAE = 0.108; RMSE = 0.143; and R2 = 0.517 for S. haematobium, and with the corresponding figures for S. mansoni being 0.053; 0.082; and 0.458. Based on this optimal model, the current total schistosomiasis prevalence in Zimbabwe under MDA implementation was 19.8%, with that of S. haematobium at 13.8% and that of S. mansoni at 7.1%, requiring annual MDA based on a population of 3,003,928. Without MDA, the current total schistosomiasis prevalence would be 23.2%, that of S. haematobium 17.1% and that of S. mansoni prevalence at 7.4%, requiring annual MDA based on a population of 3,521,466. The study reveals that MDA alone is insufficient for schistosomiasis elimination, especially that due to S. mansoni. This study predicts a moderate prevalence of schistosomiasis in Zimbabwe, with its elimination requiring comprehensive control measures beyond the currently used strategies, including health education, snail control, population surveillance and environmental management.

Universal scales of electronegativity and ionicity from electron scattering factors.

Electronegativity and ionicity are important but difficult concepts. In this work, we present the universal scale of electronegativity by utilizing electron scattering factors. A mapping of our proposed "scattering electronegativity" with Pauling electronegativity and other electronegativity scales is given. Two new ionicity scales based on electron scattering factors are also proposed and compared with Philips's ionicity and Pauling's ionicity. Although electron scattering factors are based on neutral, free, atomic features, scattering electronegativity and ionicity are able to provide rich charge or bonding information of materials in molecules or solid states. Our newly proposed electronegativity scale satisfies the metalloid band criterion (or Si rule). A new Mg rule and a new concept of critical ionicity gap are proposed, successfully distinguishing between the four-fold and six-fold coordinates in the ANB8-N crystals.