Potato glycoside alkaloids exhibit antifungal activity by regulating the tricarboxylic acid cycle pathway of Fusarium solani.

Fusarium solani is a pathogenic fungus that causes significant harm, leading to crop yield reduction, fruit quality reduction, postharvest decay, and other diseases. This study used potato glycoside alkaloids (PGA) as inhibitors to investigate their effects on the mitochondrial structure and tricarboxylic acid (TCA) cycle pathway of F. solani. The results showed that PGA could inhibit the colony growth of F. solani (54.49%), resulting in the disappearance of the mitochondrial membrane and the loss of contents. PGA significantly decreased the activities of aconitase (ACO), isocitrate dehydrogenase (IDH), α-ketoglutarate dehydrogenase (α-KGDH), succinate dehydrogenase (SDH), fumarase (FH), malate dehydrogenase (MDH), succinyl-CoA synthetase (SCS), and increased the activity of citrate synthase (CS) in F. solani. After PGA treatment, the contents of acetyl coenzyme A (CoA), citric acid (CA), malic acid (L-MA), and α-ketoglutaric acid (α-KG) in F. solani were significantly decreased. The contents of isocitric acid (ICA), succinyl coenzyme A (S-CoA), succinic acid (SA), fumaric acid (FA), and oxaloacetic acid (OA) were significantly increased. Transcriptomic analysis showed that PGA could significantly affect the expression levels of 19 genes related to TCA cycle in F. solani. RT-qPCR results showed that the expression levels of ACO, IDH, α-KGDH, and MDH-related genes were significantly down-regulated, and the expression levels of SDH and FH-related genes were significantly up-regulated, which was consistent with the results of transcriptomics. In summary, PGA can achieve antifungal effects by reducing the tricarboxylic acid cycle's flow and regulating key genes' expression levels. This study reveals the antifungal mechanism of PGA from the perspective of TCA cycle, and provides a theoretical basis for the development and application of PGA as a biopesticide.

Electro-Responsive Breathing Transition of Conductive Hydrogel for Broadband Kinetic Energy Harvesting.

Reclaiming kinetic energy from vibrating machines holds great promise for sustainable energy harvesting technologies. Nevertheless, the impulsive current induced by vibrations is incompatible with conventional energy storage devices. The energy-management system necessitates novel designs of soft materials for lightweight, miniaturized, and integrated high-frequency electrochemical devices. Here, this work develops a conductive hydrogel with an electro-responsive polymeric network. The electro-responsive breathing transition of the crosslinking points facilitates the expeditious formation of a localized electrolyte layer. This layer features an exceedingly high local charge density, surpassing that of a saturated electrolyte solution by an order of magnitude, and thus enabling rapid charge transport under the influence of an applied voltage. The micro-capacitor based on the gel exhibits record-high capacitance of ≈2 mF cm-2 when the frequency of energy input reaches up to 104  Hz. This work also demonstrates a prototype battery charger that harvests energy from a running car engine. This study presents a feasible strategy for waste energy recycling using integrated electrochemical devices, opening a new avenue for ambient energy management.

Association between meteorological factors and varicella incidence: a multicity study in Yunnan Province, China.

This multicenter study aimed to investigate the relationship between varicella incidence and meteorological factors including mean temperature, relative humidity, sunshine duration, diurnal temperature difference, wind speed, and rainfall, as previous studies have produced varying results. Our study also sought to identify potential sources of heterogeneity. Data on reported daily varicella numbers and meteorological factors were collected for 14 cities in Yunnan Province from 2017 to 2021. A distribution-lagged nonlinear model was constructed to explore the relationship between meteorological conditions and varicella incidence in each included city. We then used multiple meta-regression to explore sources of heterogeneity using demographic economics indicators, air pollutants, and geographic location as potential modifiers. The cumulative hazard effect plot showed an inverted S-shape for the relationship between temperature and varicella, with the smallest RR (relative risk) (0.533, 95% CI: 0.401-0.708) at temperatures up to 27.2 °C. The maximum RR (1.171, 95% CI: 1.001-1.371) was obtained when the relative humidity was equal to 98.5%. The RR (1.164, 95% CI: 1.002-1.352) was greatest at a diurnal temperature range of 2 °C (1.164, 95% CI: 1.002-1.352) and least (0.913, 95% CI: 0.834-0.999) at a diurnal temperature range of 16.1 °C. The maximum RR (1.214, 95% CI: 1.089-1.354) was obtained at 0 h of sunshine, and the minimum RR (0.808, 95% CI: 0.675-0.968) was obtained at 12.4 h of sunshine. The RR (0.792, 95% CI: 0.633-0.992) was minimum at a wind velocity of 4.8 m/s. Residual heterogeneity ranged from 1 to 42.7%, with PM10 (particles with an aerodynamic diameter less than 10 µm), GDP (gross domestic product), and population density explaining some of this heterogeneity. The temperature has a dual effect on varicella incidence. Varicella cases are negatively correlated with diurnal temperature range, sunshine duration, and wind speed, and positively correlated with relative humidity. GDP and PM10 may have a significant role in altering the association between temperature and varicella, while PM10 and population density may alter the association between wind velocity and varicella.

Better efficacy of triple antibiotics therapy for human brucellosis: A systematic review and meta-analysis.

BACKGROUND: The treatment of brucellosis suffers from a high recurrence rate and drug resistance. Our study researched the differences in efficacy and side effects between triple antibiotics therapy and dual antibiotics therapy in the treatment of brucellosis through a systematic review and meta-analysis. METHODS: We searched 4 English electronic databases and 2 Chinese electronic databases for randomized controlled trials and cohort studies published through September 2022 on the use of triple antibiotics versus dual antibiotics in the treatment of brucellosis. Overall outcome indicators were therapeutic failure rate, relapse rate, overall therapeutic failure rate, and side effect rate. Relative risk (RR) and 95% confidence intervals (95% CIs) were used as summary statistics. A fixed-effects model was used to combine the overall effect sizes. RESULTS: The meta-analysis included 15 studies consisting of 11 randomized controlled trials and 4 cohort studies. Triple antibiotics showed better efficacy than dual antibiotics in a comparison of 3 overall outcome indicators (therapeutic failure rate (RR 0.42; 95% CI 0.30 to 0.59 heterogeneity P = 0.29, I2 = 15%), relapse rate (RR 0.29; 95% CI 0.18 to 0.45 heterogeneity P = 0.88, I2 = 0%), and overall therapeutic failure rate (RR 0.37; 95% CI 0.28 to 0.48 heterogeneity P = 0.35, I2 = 9%)). The incidence of side effects in patients with brucellosis treated with triple antibiotics was not significantly different from that in brucellosis patients treated with dual antibiotics (RR 0.85; 95% CI 0.67 to 1.06 heterogeneity P = 0.1, I2 = 35%). Sensitivity analyses showed robust results and Peter's test showed no publication bias. The results of subgroup analyses for the research type, drugs, and type of brucellosis were largely consistent with the overall outcome indicators, indicating the reliability and robustness of the overall results. CONCLUSIONS: In the treatment of brucellosis, triple antibiotics have better efficacy than dual antibiotics and do not increase the incidence of side effects.

Predictive value of radiomics-based machine learning for the disease-free survival in breast cancer: a systematic review and meta-analysis.

Purpose: This study summarized the previously-published studies regarding the use of radiomics-based predictive models for the identification of breast cancer-associated prognostic factors, which can help clinical decision-making and follow-up strategy. Materials and methods: This study has been pre-registered on PROSPERO. PubMed, Embase, Cochrane Library, and Web of Science were searched, from inception to April 23, 2022, for studies that used radiomics for prognostic prediction of breast cancer patients. Then the search was updated on July 18, 2023. Quality assessment was conducted using the Radiomics Quality Score, and meta-analysis was performed using R software. Results: A total of 975 articles were retrieved, and 13 studies were included, involving 5014 participants and 35 prognostic models. Among the models, 20 models were radiomics-based and the other 15 were based on clinical or pathological information. The primary outcome was Disease-free Survival (DFS). The retrieved studies were screened using LASSO, and Cox Regression was applied for modeling. The mean RQS was 18. The c-index of radiomics-based models for DFS prediction was 0.763 (95%CI 0.718-0.810) in the training set and 0.702 (95%CI 0.637-0.774) in the validation set. The c-index of combination models was 0.807 (95%CI0.736-0.885) in the training set and 0.840 (95%CI 0.794-0.888) in the validation set. There was no significant change in the c-index of DFS at 1, 2, 3, and over 5 years of follow-up. Conclusion: This study has proved that radiomics-based prognostic models are of great predictive performance for the prognosis of breast cancer patients. combination model shows significantly enhanced predictive performance. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022332392.

Effect of Potato Glycoside Alkaloids on Energy Metabolism of Fusarium solani.

Fusarium solani is one of the primary pathogens causing root rot of wolfberry. The aims of this study were to investigate the inhibitory effect of potato glycoside alkaloids (PGA) on F. solani and its energy metabolism. In this study, the effects of PGA treatment on the growth and development of F. solani were investigated and the changes in the glycolytic pathway (EMP), ATPase activity, mitochondrial complex activity, mitochondrial structure, and energy charge level were analyzed to elucidate the possible antifungal mechanism of PGA on F. solani. The results showed that PGA treatment inhibited the colony growth, biomass, and spore germination of F. solani. PGA treatment reduced the glucose content and Hexokinase (HK) activity of F. solani, but increased the activity of Fructose-6-Phosphate Kinase (PFK) and Pyruvate Kinase (PK) and promoted the accumulation of pyruvic acid. In addition, PGA treatment inhibited the activities of H+-ATPase, Ca2+-ATPase, and mitochondrial complex IV, increased the mitochondrial inner membrane Ca2+ content and mitochondrial membrane permeability transition pore, and decreased the contents of ATP, ADP, and AMP as well as the energy charge. These results indicate that PGA treatment inhibits the growth and development of F. solani, activates the glycolysis pathway, inhibits ATPase activity and mitochondrial complex activity, and destroys the structure and function of mitochondrial membrane, resulting in a lower energy charge level.

Follow-up outcomes of asymptomatic brucellosis: a systematic review and meta-analysis.

Balancing the potentially serious outcomes of asymptomatic brucellosis and "waiting" for treatment in clinical practice is an urgent issue. Therefore, we assessed the follow-up outcomes and epidemiological characteristics of asymptomatic brucellosis in the absence of treatment to provide evidence-based clinical clues. We searched eight databases in which 3610 studies from 1990 to 2021 were related to the follow-up outcomes of asymptomatic brucellosis. Thirteen studies, involving 107 cases, were finally included. Regarding the follow-up outcomes, we examined the presence or absence of symptoms and decreased serum agglutination test (SAT) titre. During the 0.5-18 months follow-up period, the pooled prevalence of appearing symptomatic was 15.4% (95% CI 2.1%-34.3%), cases that remained asymptomatic were 40.3% (95% CI 16.6%-65.8%), and decreased SAT titre was observed in 36.5% (95% CI 11.6%-66.1%). Subgroup analysis indicated that the pooled prevalence of appearing symptomatic with follow-up times of less than 6 months, 6-12 months, and 12-18 months was 11.5%, 26.4%, and 47.6%, respectively. The student subgroup had a higher prevalence of symptoms (46.6%) than the occupational and family populations. In conclusion, asymptomatic brucellosis has a high likelihood of appearing symptomatic and its severity may be underestimated. Active screening of occupational and family populations should be enhanced, and special attention should be paid to high-titre students for early intervention, if necessary. Additionally, future prospective, long-term, and large-sample follow-up studies are essential.

Prehension kinematics in humans and macaques.

Nonhuman primates, especially rhesus macaques, have been a dominant model to study sensorimotor control of the upper limbs. Indeed, human and macaques have similar hands and homologous neural circuits to mediate manual behavior. However, few studies have systematically and quantitatively compared the manual behaviors of the two species. Such comparison is critical for assessing the validity of using the macaque sensorimotor system as a model of its human counterpart. In this study, we systematically compared the prehensile behaviors of humans and rhesus macaques using an identical experimental setup. We found human and macaque prehension kinematics to be generally similar with a few subtle differences. Although the structure of the preshaping hand postures is similar in humans and macaques, human postures are more object-specific and human joints are less intercorrelated. Conversely, monkeys demonstrate more stereotypical preshaping behaviors that are common across all objects and more variability in their postures across repeated presentations of the same object. Despite these subtle differences in manual behavior between humans and monkeys, our results bolster the use of the macaque model to understand the neural mechanisms of manual dexterity in humans.NEW & NOTEWORTHY Macaques have been a dominant animal model to study the neural mechanisms of human dexterity because they exhibit complex manual behavior. We show that the kinematics of prehension, a critical dexterous behavior, are largely similar in humans and macaques. However, human preshaping postures are more object-specific and the movement of human digits is less correlated with each other. The thumb, index, and wrist are major drivers of these interspecies differences.

Unexpected complexity of everyday manual behaviors.

How does the brain control an effector as complex and versatile as the hand? One possibility is that neural control is simplified by limiting the space of hand movements. Indeed, hand kinematics can be largely described within 8 to 10 dimensions. This oft replicated finding has been construed as evidence that hand postures are confined to this subspace. A prediction from this hypothesis is that dimensions outside of this subspace reflect noise. To address this question, we track the hand of human participants as they perform two tasks-grasping and signing in American Sign Language. We apply multiple dimension reduction techniques and replicate the finding that most postural variance falls within a reduced subspace. However, we show that dimensions outside of this subspace are highly structured and task dependent, suggesting they too are under volitional control. We propose that hand control occupies a higher dimensional space than previously considered.

Synergy with interferon-lambda 3 and sorafenib suppresses hepatocellular carcinoma proliferation.

Hepatocellular carcinoma (HCC) is a common and fatal malignancy of the liver. Sorafenib is a small molecule multikinase inhibitor that acts against different cancer cell lines and is used for the treatment of HCC. However, some advanced HCC patients fail to respond to sorafenib, and those who do lack a meaningful clinical benefit. Interferon-lambda 3 (IFN-λ3) is a type III interferon with antiviral, antiproliferative, and immunomodulatory functions. Here, we evaluated the use of IFN-λ3 as an adjuvant treatment with sorafenib in HCC. In the present study, CCK-8 and colony formation assay results showed that treatment with a combination of IFN-λ3 and sorafenib suppresses the viability of HepG2 and SMMC7721 liver cancer cell lines more than treatment with either alone. In addition, flow cytometry results confirmed that treatment with a combination of IFN-λ3 and sorafenib promotes the loss of mitochondrial membrane potential and induces the production of ROS more than treatment with either alone. Furthermore, using a subcutaneous SMMC7721 tumor model, treatment with a combination of IFN-λ3 and sorafenib significantly reduced the tumor growth/volume and induced apoptosis compared to treatment with sorafenib alone. These results show that combined treatment with IFN-λ3 and sorafenib facilitates a synergistic effect on suppressing HCC cancer growth and promoting cell apoptosis in vitro and in vivo. Thus, IFN-λ3 in combination with sorafenib might prove to be a useful adjunctive strategy for the clinical treatment of HCC.

An Explanation of the Underlying Mechanisms for the In Vitro and In Vivo Antiurolithic Activity of Glechoma longituba.

Purpose. To use in vitro and in vivo models to evaluate Glechoma longituba extract to provide scientific evidence for this extract's antiurolithic activity. Materials and Methods. Potassium citrate was used as a positive control group. Oxidative stress (OS) markers and the expression of osteopontin (OPN) and kidney injury molecule-1 (KIM-1) were measured to assess the protective effects of Glechoma longituba. Multiple urolithiasis-related biochemical parameters were evaluated in urine and serum. Kidneys were harvested for histological examination and the assessment of crystal deposits. Results. In vitro and in vivo experiments demonstrated that treatment with Glechoma longituba extract significantly decreased calcium oxalate- (CaOx-) induced OPN expression, KIM-1 expression, and OS compared with the positive control group (P < 0.05). Additionally, in vivo rats that received Glechoma longituba extract exhibited significantly decreased CaOx deposits and pathological alterations (P < 0.05) compared with urolithic rats. Significantly lower levels of oxalate, creatinine, and urea and increased citrate levels were observed among rats that received Glechoma longituba (P < 0.05) compared with urolithic rats. Conclusion. Glechoma longituba has antiurolithic effects due to its possible combined effects of increasing antioxidant levels, decreasing urinary stone-forming constituents and urolithiasis-related protein expression, and elevating urinary citrate levels.