The causal effects of genetically predicted alcohol consumption on endometrial cancer risk from a Mendelian randomization study.

Endometrial cancer (EC) is a common gynecological tumor in females with an increasing incidence over the past few decades. Alcohol consumption has been linked to the occurrence of various cancers; However, epidemiological studies have shown inconsistent associations between alcohol consumption and EC risk. In order to avoid the influence of potential confounding factors and reverse causality in traditional epidemiological studies, we used a method based on genetic principles-Mendelian randomization (MR) analysis to test whether there is a causal relationship between alcohol consumption and EC. MR analysis was conducted using publicly available summary-level data from genome-wide association studies (GWAS). Fifty-seven single nucleotide polymorphisms (SNPs) were extracted as instrumental variables for alcohol exposure from the GWAS and Sequencing Consortium of Alcohol and Nicotine GWAS summary data involving 941,287 participants of European ancestry. SNPs for EC were obtained from the Endometrial Cancer Association Consortium, the Endometrial Cancer Epidemiology Consortium, and the UK Biobank, involving 121,885 European participants. The inverse variance weighted (IVW) method was used as the primary method to estimate the causal effect, and the MR-Egger regression and weighted median method were used as supplementary methods. Sensitivity analyses were conducted using the Mendelian Randomization Pleiotropy RESidual Sum and Outlier global test, MR-Egger intercept test, and leave-one-out analysis to evaluate the impact of pleiotropy on causal estimates. An increase of 1 standard deviation of genetically predicted log-transformed alcoholic drinks per day was associated with a 43% reduction in EC risk [odds ratio (OR) = 0.57, 95% confidence interval (CI) 0.41-0.79, P < 0.001]. Subgroup analysis of EC revealed that alcohol consumption was a protective factor for endometrioid endometrial cancer (EEC) (OR = 0.56, 95% CI 0.38-0.83, P = 0.004) but not for non-endometrioid endometrial cancer (NEC) (OR = 1.36, 95% CI 0.40-4.66, P = 0.626). The MR-Egger regression and weighted median method yielded consistent causal effects with the IVW method. The consistent results of sensitivity analyses indicated the reliability of our causal estimates. Additionally, alcohol consumption was associated with decreased human chorionic gonadotropin (HCG) and insulin-like growth factor 1 (IGF1) levels. This MR study suggests that genetically predicted alcohol consumption is a protective factor for EC, particularly for EEC, and this protective effect may be mediated through the reduction of HCG and IGF1.

Arresting the G2/M phase empowers synergy in magnetic nanomanipulator-based cancer mechanotherapy and chemotherapy.

Using mechanical cues for cancer cells can realize precise control and efficient therapeutic effects. However, the cell cycle-specific response for dynamic mechanical manipulation is barely investigated. Here, RGD-modified iron oxide nanomanipulators were utilized as the intracellular magneto-mechanical transducers to investigate the mechanical impacts on the cell cycle under a dynamic magnetic field for cancer treatment. The G2/M phase was identified to be sensitive to the intracellular magneto-mechanical modulation with a synergistic treatment effect between the pretreatment of cell cycle-specific drugs and the magneto-mechanical destruction, and thus could be an important mechanical-targeted phase for regulation of cancer cell death. Finally, combining the cell cycle-specific drugs with magneto-mechanical manipulation could significantly inhibit glioma and breast cancer growth in vivo. This intracellular mechanical stimulus showed cell cycle-dependent cytotoxicity and could be developed as a spatiotemporal therapeutic modality in combination with chemotherapy drugs for treating deep-seated tumors.

Rare, late onset of immune checkpoint inhibitor-induced type 1 diabetes mellitus in a patient with small-cell lung cancer treated with serplulimab: a case report and review of the literature.

BACKGROUND: As a newly approved immune checkpoint inhibitor in China, serplulimab has been widely used in the immunotherapy of tumors. However, the immune-related adverse events of immune checkpoint inhibitors should not be ignored. Although immune checkpoint inhibitor-induced type 1 diabetes mellitus is a rare complication, it may cause diabetic ketoacidosis and endanger the lives of patients. CASE PRESENTATION: This case report describes a 55-year-old male of Han nationality from China diagnosed with small-cell lung cancer with multiple metastases who experienced an adverse event of type 1 diabetes mellitus 68 weeks after receiving serplulimab therapy. The patient presented with typical symptoms of diabetic ketoacidosis, including severe thirst, nausea, vomiting, deep respirations, and stupor. Despite the absence of diabetes-related autoantibodies, the patient had extremely low levels of insulin and C-peptide release. Other potential causes of diabetes were ruled out, confirming the condition as serplulimab-induced immune checkpoint inhibitor-induced type 1 diabetes mellitus. After aggressive treatment to correct diabetic ketoacidosis, the patient's blood glucose levels stabilized and symptoms of diabetes improved significantly, although long-term insulin maintenance therapy was necessary. CONCLUSION: This case highlights a rare, late-onset adverse event of immune checkpoint inhibitor-induced type 1 diabetes mellitus that may be overlooked during treatment with serplulimab. The monitoring of blood glucose levels and early signs and symptoms of diabetes cannot be relaxed at the late stage of treatment, even if patients do not have elevated blood glucose levels before and during the middle stage of treatment.

Comparison of the efficacy of fish oil and probiotic supplementation on glucose and lipid metabolism in patients with type 2 diabetes: a systematic review and network meta-analysis.

BACKGROUND: Abnormalities in glucose and lipid metabolism contribute to the progression and exacerbation of type 2 diabetes mellitus (T2DM). Fish oil and probiotics are dietary supplements that have the potential to improve glucose and lipid metabolism. However, their efficacy remains unclear in T2DM patients. METHODS: PubMed, Embase, and the Cochrane Library were retrieved to collect randomized controlled trials (RCTs) on the efficacy of fish oil or probiotic supplementation in T2DM patients from the database inception to December 13, 2023. Primary outcome indicators encompassed glycated hemoglobin (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR) and blood lipid profile (triglyceride (TG) and total cholesterol (TC). Secondary outcome indicators included inflammatory markers such as tumor necrosis factor -α (TNF-α) and adipocytokine (including leptin and adiponectin). The R software was used for statistical analysis, and GraphPad Prism was used for figure rendering. RESULTS: A total of 60 RCTs involving 3845 T2DM patients were included in the analysis. The results showed that the probiotics (Bifidobacterium, Lactobacillus, Lactococcus, Propionibacterium, etc.) were more effective in reducing HOMA-IR than fish oil (Surca = 0.935). Bifidobacterium demonstrated the highest efficacy in reducing HbA1c levels (Surca = 0.963). Regarding lipid metabolism, fish oil was superior to probiotics in lowering TG and TC levels (Surca values of 0.978 and 0.902, respectively). Furthermore, fish oil outperformed probiotics in reducing TNF-α (Surca = 0.839) and leptin (Surca = 0.712), and increasing adiponectin levels (Surca = 0.742). Node-splitting analysis showed good consistency (P > 0.05 for direct, indirect, and network comparison across various interventions). CONCLUSIONS: In T2DM patients, fish oil was more effective than probiotics in regulating lipid metabolism. Probiotics outperformed fish oil in regulating glucose metabolism particularly; specifically, Bifidobacterium showed higher efficacy in reducing blood glucose.

Efficacy and safety analysis of stereotactic body radiotherapy for brain multi-metastases in non-small cell lung cancer patients.

BACKGROUND: Lung cancer is prone to metastasize to the brain, which is difficult for surgery and leads to poor prognosis due to poor chemotherapy efficacy. OBJECTIVE: Our aim is to evaluate the efficacy and safety of stereotactic body radiotherapy (SBRT) for brain multi-metastases. METHODS: In the retrospective study, a total of 51 non-small cell lung cancer (NSCLC) patients with brain multi-metastases (3-5 metastases) receiving SBRT in the local hospital between 2016 and 2019 were enrolled for analyzing the efficacy and safety of SBRT. The primary endpoints included 1-year local control rate, radiotherapy toxicity, overall survival and progression-free survival. RESULTS: The median follow-up for the enrolled patients was 21 months, and the 1-year and 2-year OS rates were 82.4% and 45.1%, respectively. Demographic analysis showed no significant differences between SBRT alone and combination with whole brain radiotherapy in clinical characteristics including age, gender and Eastern Cooperative Oncology Group performance status. The 1-year local control rate was 77.3% (17/22) for SBRT alone, which was comparable to 79.3% (23/29) of combined radiotherapy. Cox proportional hazard regression demonstrated that the prognostic benefit of combining WBRT was not significantly superior to SBRT alone (HR = 0.851, P= 0.263). Their radiotherapy toxicity rate was lower in SBRT alone group (13.6%, vs. 44.8% for combination; P= 0.017). CONCLUSION: The current research suggested that SBRT alone could effectively relieve tumor burden and improve the prognosis and quality of life for NSCLC patients with brain multi-metastases, which should be validated in further prospective clinical trials.

A General Method to Access Sterically Encumbered Geminal Bis(boronates) via Formal Umpolung Transformation of Terminal Diboron Compounds.

General methods for the preparation of geminal bis(boronates) are of great interest due to their widespread applications in organic synthesis. While the terminal gem-diboron compounds are readily accessible, the construction of the sterically encumbered, internal analogues has remained a prominent challenge. Herein, we report a formal umpolung strategy to access these valuable building blocks. The readily available 1,1-diborylalkanes were first converted into the corresponding α-halogenated derivatives, which then serve as electrophilic components, undergoing a formal substitution with a diverse array of nucleophiles to form a series of C-C, C-O, C-S, and C-N bonds. This protocol features good tolerance to steric hindrance and a wide variety of functional groups and heterocycles. Notably, this strategy can also be extended to the synthesis of diaryl and terminal gem-diboron compounds, therefore providing a general approach to various types of geminal bis(boronates).

A Lysosome-Targeted Magnetic Nanotorquer Mechanically Triggers Ferroptosis for Breast Cancer Treatment.

Targeting ferroptosis has attracted exponential attention to eradicate cancer cells with high iron-dependent growth. Increasing the level of intracellular labile iron pool via small molecules and iron-containing nanomaterials is an effective approach to induce ferroptosis but often faces insufficient efficacy due to the fast drug metabolism and toxicity issues on normal tissues. Therefore, developing a long-acting and selective approach to regulate ferroptosis is highly demanded in cancer treatment. Herein, a lysosome-targeted magnetic nanotorquer (T7-MNT) is proposed as the mechanical tool to dynamically induce the endogenous Fe2+ pool outbreak for ferroptosis of breast cancer. T7-MNTs target lysosomes via the transferrin receptor-mediated endocytosis in breast cancer cells. Under the programmed rotating magnetic field, T7-MNTs generate torques to trigger endogenous Fe2+ release by disrupting the lysosomal membrane. This magneto-mechanical manipulation can induce oxidative damage and antioxidant defense imbalance to boost frequency- and time-dependent lipid peroxidization. Importantly, in vivo studies show that T7-MNTs can efficiently trigger ferroptosis under the magnetic field and play as a long-acting physical inducer to boost ferrotherapy efficacy in combination with RSL3. It is anticipated that this dynamic targeted strategy can be coupled with current ferroptosis inducers to achieve enhanced efficacy and inspire the design of mechanical-based ferroptosis inducers for cancer treatment.

Triglyceride-Glucose Index as a Predictor of Lower Extremity Arterial Disease in Patients with Diabetes: A Hospitalized Population Retrospective Study.

BACKGROUND: The triglyceride-glucose (TyG) index is a new, simple, and inexpensive marker of insulin resistance that is becoming increasingly important as a promising predictor of diseases such as atherosclerosis. Atherosclerosis is the main cause of lower extremity arterial disease (LEAD). In this study, we investigated the relationship between TyG index values and LEAD risk in patients with diabetes. METHODS: Patients with diabetes hospitalized at the Endocrinology Department of our hospital from June 1, 2021, to May 31, 2022, were retrospectively included. Baseline data, biochemical indicators, and ankle-brachial index values were collected. Statistical methods were used to assess the relationship between TyG index values and the risk of LEAD. RESULTS: A total of 1,040 hospitalized patients with diabetes were included, they were divided into the LEAD group with 168 patients and the no LEAD group with 872 patients. TyG index values in the LEAD group were higher than those in the no LEAD group (9.94 ± 0.78 vs. 9.36 ± 0.70, P < 0.001). TyG index values were independently correlated with LEAD risk in patients with diabetes (odds ratio = 3.92, 95% confidence interval (CI): 2.92-5.26, P < 0.001) in multivariate logistic regression analysis after adjusting for different risk factors (all P < 0.05). The area under the receiver operating characteristic curve was 0.72 (95% CI: 0.68-0.76) when TyG index values were used to diagnose LEAD in patients with diabetes. When Youden's index reached the maximum value of 0.34, the optimal TyG index threshold for predicting the onset of diabetic LEAD was 9.56, sensitivity was 71.1%, and specificity was 63.0%. CONCLUSIONS: Increases in TyG index values were associated with the risk of LEAD in patients with diabetes and, thus, may be used as a predictor of LEAD in this patient population, especially in primary care institutions with relatively few resources.

Comparison of healing effectiveness of different debridement approaches for diabetic foot ulcers: a network meta-analysis of randomized controlled trials.

Objectives: The choice of the debridement method is very important for the healing of diabetic foot ulcers (DFUs), but the relative effectiveness of different debridement methods in the healing of DFUs remains unclear. This study conducted a network meta-analysis of the relative healing effectiveness of different debridement methods in patients with DFUs. Methods: We performed a literature search in PubMed, Embase, and Cochrane Library from database inception up to 30 June 2023 for screening randomized controlled trials on the healing effectiveness of debridement in DFUs. Outcome measures included ulcer healing rate and ulcer area reduction rate. The Cochrane Risk Bias Tool, version 2.0, was used to assess the risk of bias in the included trials. R software was used for performing statistical analysis and GraphPad Prism was used for image plotting. Results: A total of 19 randomized controlled trials were included, and 900 patients with DFUs were assessed in this analysis. The proteolytic fraction from the latex of Vasconcellea cundinamarcensis (P1G10) in enzymatic debridement showed the best ulcer healing rate (SURCA = 0.919) when compared with the standard of care (SOC) group, with a mean difference (MD) and 95% confidence interval (CI) of 1.40 (0.57, 2.36). Kiwifruit extract demonstrated the best effect on the ulcer area reduction rate (SURCA = 0.931), when compared with that in the SOC group, with an MD and 95% CI of 0.47 (0.27, 0.66). Conclusion: Enzymatic debridement was superior to other debridement methods in terms of ulcer healing rate and ulcer area reduction rate in patients with DFUs. However, as the quality of the included trials is low, enzymatic debridement can be used as a candidate debridement method in addition to sharp-based debridement in clinical practice. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023441715.

The impact of superselective adrenal artery embolization on renal function in patients with primary aldosteronism: a prospective cohort study.

Superselective adrenal artery embolization (SAAE) is an effective treatment for patients with primary aldosteronism (PA). However, the impact of SAAE on renal function in the PA population remains uncertain. We investigated the estimated glomerular filtration rate (eGFR) and age, sex, body mass index, and diabetes-specific percentiles of eGFR residuals in 182 PA patients treated with SAAE in a prospective cohort from Nanchang SAAE in treating PA registry study. Data suggest that SAAE caused a significant decrease in eGFR from 91.9 ± 26.1 to 88.7 ± 24.1 ml/min/1.73 m2 (p < 0.05) after a median follow-up of 8 months in PA patients. Patients experienced a significant decrease in eGFR from 110.6 ± 18.9 to 103.8 ± 18.2 ml/min/1.73 m2 (p < 0.001) and a very slight increase from 71.1 ± 14.8 to 71.8 ± 17.8 ml/min/1.73 m2 (p = 0.770) with baseline eGFR ≥90 and <90 ml/min/1.73 m2, respectively. Patients with high eGFR residuals (glomerular hyperfiltration) experienced a significant decrease in their eGFR levels from 123.1 ± 22.6 to 105.0 ± 18.6 ml/min/1.73 m2 (p < 0.001). In contrast, there was no significant impact of SAAE on the eGFR of patients with normal or low eGFR residuals. The very early eGFR changes (24 h after SAAE) best predicted the effect of SAAE on eGFR changes after median of eight months in PA patients. On the whole, SAAE seems to have a beneficial impact on renal function in patients with PA, the results of which vary depending on the patient's baseline eGFR and glomerular hyperfiltration status.

Safety Review of Radiotherapy for Tumor Patients with Implantable Cardiac Pacemaker.

Permanent pacemaker implantation is one of the most effective treatments for chronic arrhythmia. However, there is a certain risk associated with radiation therapy in cancer patients with implantable cardiac pacemakers. To prevent radiotherapy-induced pacemaker failure, there are established medical guidelines for the use of pacemakers in patients undergoing radiotherapy. With advancements in science and technology, the variety of available pacemakers has considerably increased, and radiotherapy equipment has also been updated. Given the variations in irradiation methods and the types of radiation used in clinical practice, there is a pressing need for international consensus on the regulations governing the use of cardiac pacemakers in cancer patients. Currently, many countries lack clinical guidelines for radiotherapy in cancer patients with cardiac pacemakers. This review summarizes recent reports and studies from PubMed (National Center for Biotechnology Information) regarding the safety of radiotherapy in cancer patients with implanted cardiac pacemakers, and provides valuable insights for clinical practice.

Production of AmpC ß-Lactamase and Development of a Competitive Array for Discriminative Determination of Cephalosporins in Milk.

In this study, AmpC ß-lactamase of Escherichia coli was expressed, and its intermolecular interaction mechanisms with 15 cephalosporins (CPs) were studied by using a molecular docking technique. Results showed that this enzyme mainly interacted with the ß-lactam ring of these CPs, and the key contacting amino acids were Ser80 and Ser228. The AmpC ß-lactamase was combined with 5 horseradish peroxidase-labeled conjugates to develop a direct competitive array on a microplate for determination of 15 drugs in milk. Due to the use of principal component analysis method to analyze the data, this method could discriminate the 15 drugs at the concentration as low as 10 ng/mL. The detection results for the unknown milk samples were consistent with those obtained by the liquid chromatography-mass spectrometry method. As a general comparison, this method is better than the previous antibody-based and receptor-based detection methods for CPs. This is the first paper reporting a competitive array for discriminative determination of a class of small-molecule substances.

Anti-infection effects of heparin on SARS-CoV-2 in a diabetic mouse model.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in more severe syndromes and poorer outcomes in patients with diabetes and obesity. However, the precise mechanisms responsible for the combined impact of corona virus disease 2019 (COVID-19) and diabetes have not yet been elucidated, and effective treatment options for SARS-CoV-2-infected diabetic patients remain limited. To investigate the disease pathogenesis, K18-hACE2 transgenic (hACE2 Tg) mice with a leptin receptor deficiency (hACE2-Lepr -/-) or high-fat diet (hACE2-HFD) background were generated. The two mouse models were intranasally infected with a 5×10 5 median tissue culture infectious dose (TCID 50) of SARS-CoV-2, with serum and lung tissue samples collected at 3 days post-infection. The hACE2-Lepr -/- mice were then administered a combination of low-molecular-weight heparin (LMWH) (1 mg/kg or 5 mg/kg) and insulin via subcutaneous injection prior to intranasal infection with 1×10 4 TCID 50 of SARS-CoV-2. Daily drug administration continued until the euthanasia of the mice. Analyses of viral RNA loads, histopathological changes in lung tissue, and inflammation factors were conducted. Results demonstrated similar SARS-CoV-2 susceptibility in hACE2 Tg mice under both lean (chow diet) and obese (HFD) conditions. However, compared to the hACE2-Lepr +/+ mice, hACE2-Lepr -/- mice exhibited more severe lung injury, enhanced expression of inflammatory cytokines and hypoxia-inducible factor-1α, and increased apoptosis. Moreover, combined LMWH and insulin treatment effectively reduced disease progression and severity, attenuated lung pathological changes, and mitigated inflammatory responses. In conclusion, pre-existing diabetes can lead to more severe lung damage upon SARS-CoV-2 infection, and LMWH may be a valuable therapeutic approach for managing COVID-19 patients with diabetes.

Dendroclimatic response of Pinus tabuliformis Carr. along an altitudinal gradient in the warm temperate region of China.

Introduction: Global climate change can affect the sensitivity of tree radial growth to climate factors, but the specific responses of tree radial growth to microclimate along the altitudinal gradient in the long term are still unclear. Methods: In this study, the tree-ring width chronologies of Pinus tabuliformis Carr. in Shanxi Province of China were studied at three altitude gradients (1200-1300 m (low altitude), 1300-1400 m (medium altitude) and 1400-1500 m (high altitude)) during 1958-2017. Results: The results showed that (1) the climate background could be divided into two periods based on the Mann-Kendall test analysis: 1958-1996 was a stable period (mean annual temperature (MAT)=10.25°C, mean annual precipitation (MAP)=614.39 mm), and 1997-2017 was a rapid change period (MAT=10.91°C, MAP=564.70 mm), indicating a warming and drying trend in the study region. (2) The radial growth of P. tabuliformis at different altitudes showed inconsistent variation patterns. The tree radial growth at low and medium altitudes (CV=27.01% for low altitude and CV=24.69% for medium altitude) showed larger variation amplitudes during the rapid change period than that in the stable period (CV=12.40% for low altitude and CV=18.42% for medium altitude). In contrast to the increasing trend, the tree radial growth rates at the high altitude showed a decreasing trend across years. (3) In the stable period, the radial growth of P. tabuliformis at the low altitude showed a significantly negative response to temperature and a positive response to precipitation in May and June. The tree radial growth at the medium altitude was positively related to precipitation in June and minimum temperature in February. The tree growth at the high altitude was mainly positively correlated with the temperature in May and August. In the rapid change period, the radial growth of P. tabuliformis at the low altitude was affected by more meteorological factors than that in the stable period. Medium-altitude trees were positively influenced by precipitation in June and minimum temperature in January, whereas high-altitude trees responded positively to wind speed in February. (4) Along altitudinal gradients, tree radial growth was more related to temperature than precipitation in the stable period. The tree radial growth at the high altitude during the rapid change period was only affected by wind speed in February, whereas the tree radial growth at low and medium altitudes was mainly affected by temperature to a similar extent during the two periods. Discussion: The study indicated that tree growth-climate response models could help deeply understand the impact of climate change on tree growth adaptation and would be beneficial for developing sustainable management policies for forest ecosystems in the transition zone from warm-temperate to subtropical climates.

Facile Access to Cyclopropylboronates via Stereospecific Deborylative Cyclization: A Leaving Group-Assisted Activation of Geminal Diborons.

Herein we reported a transition metal-free deborylative cyclization strategy, based on which two routes have been developed, generating racemic and enantioenriched cyclopropylboronates. The cyclization of geminal-bis(boronates) bearing a leaving group was highly diastereoselective, tolerating a few functional groups and applicable to heterocycles. When optically active epoxides were used as the starting materials, enantioenriched cyclopropylboronates could be efficiently prepared with >99 % stereospecificity. Mechanistic studies showed that the leaving group at the γ-position played a crucial role and significantly promoted the activation of the gem-diboron moiety.

Superselective adrenal arterial embolization for primary aldosteronism without lateralized aldosterone secretion: an efficacy and safety, proof-of-principle study.

Superselective adrenal arterial embolization (SAAE) appears to be beneficial in primary aldosteronism (PA) patients with lateralized aldosterone secretion (unilateral PA). As confirmed by adrenal vein sampling (AVS), nearly 40% of PA patients would be PA without lateralized aldosterone secretion (bilateral PA). We aimed to investigate the efficacy and safety of SAAE on bilateral PA. We identified 171 bilateral PA patients from 503 PA patients who completed AVS. Thirty-eight bilateral PA patients received SAAE, and 31 completed a median 12-month clinical follow-up. The blood pressure and biochemical improvements of these patients were carefully analyzed. 34% of patients were identified as bilateral PA. Plasma aldosterone concentration, plasma renin activity, and aldosterone/renin ratio (ARR) were significantly improved 24-h after SAAE. SAAE was associated with 38.7% and 58.6% of complete/partial clinical and biochemical success within a median 12-month follow-up. A significant reduction in left ventricular hypertrophy was shown in patients who obtained complete biochemical success compared with partial/absent biochemical success. SAAE was associated with a more apparent nighttime blood pressure reduction than daytime blood pressure reduction in patients with complete biochemical success. No major adverse safety events related to SAAE were reported during the intraoperative, postoperative, and follow-up periods. SAAE was associated with blood pressure and biochemical improvements in part of bilateral PA and appeared safe. The biochemistry success was accompanied by improved cardiac remodeling and a more prominent decrease in nocturnal blood pressure. This study was part of a trial registered with the Chinese Clinical Trial Registry, number ChiCTR2100047689.

A New Evidential Reasoning Rule Considering Interval Uncertainty and Perturbation.

The evidential reasoning (ER) rule has been widely applied in the multiple attribute decision making (MADM), which makes the decision-making process transparent and credible by using a belief structure. To improve the ability of the ER rule in dealing with the interval uncertainty, a new interval ER (IER) rule is proposed in this article. The interval uncertainty is described as the interval grade in the new frame of discernment (FoD) to model the local ignorance. It is proved that the IER rule is a generalization of the ER rule. To study the influence of perturbation on the IER rule, the perturbation is first introduced to the belief structure, and the perturbation analysis (PA) is conducted for the IER rule. An optimization model is established to estimate the perturbation threshold, which can measure the effectiveness of the inference result under perturbation. Two numerical examples and a case study are carried out, respectively, to show the implementation process of the proposed IER rule and validate its effectiveness in different decision-making scenarios.

Photomagnetically Powered Spiky Nanomachines with Thermal Control of Viscosity for Enhanced Cancer Mechanotherapy.

Nanomachines with active propulsion have emerged as an intelligent platform for targeted cancer therapy. Achieving an efficient locomotion performance using an external energy conversion is a key requirement in the design of nanomachines. In this study, inspired by diverse spiky structures in nature, a photomagnetically powered nanomachine (PMN) with a spiky surface and thermally dependent viscosity tunability is proposed to facilitate mechanical motion in lysosomes for cancer mechanotherapy. The hybrid nanomachine is integrated with magnetic nanoparticles as the core and covered with gold nanotips. Physical simulations and experimental results prove that the spiky structure endows nanomachines with an obvious photomagnetic coupling effect in the NIR-II region through the alignment and orienting movement of plasmons on the gold tips. Using a coupling-enhanced magnetic field, PMNs are efficiently assembled into chain-like structures to further elevate energy conversion efficiency. Notably, PMNs with the thermal control of viscosity are efficiently propelled under simultaneously applied dual external energy sources in cell lysosomes. Enhanced mechanical destruction of cancer cells via PMNs is confirmed both in vitro and in vivo under photomagnetic treatment. This study provides a new direction for designing integrated nanomachines with active adaptability to physiological environments for cancer treatment.

Impact of myeloid differentiation protein 1 on cardiovascular disease.

Cardiovascular disease remains the leading cause of disability and mortality worldwide and a significant global burden. Many lines of evidence suggest complex remodeling responses to cardiovascular disease, such as myocardial ischemia, hypertension and valve disease, which lead to poor clinical outcomes, including heart failure, arrhythmia and sudden cardiac death (SCD). The mechanisms underlying cardiac remodeling are closely related to reactive oxygen species (ROS) and inflammation. Myeloid differentiation protein 1 (MD1) is a secreted glycoprotein known as lymphocyte antigen 86. The complex of MD1 and radioprotective 105 (RP105) is an important regulator of inflammation and is involved in the modulation of vascular remodeling and atherosclerotic plaque development. A recent study suggested that the expression of MD1 in hypertrophic cardiomyopathy (HCM) patients is decreased compared with that in donor hearts. Therefore, MD1 may play an important role in the pathological processes of cardiovascular disease and have potential clinical value. Here, this review aims to discuss the current knowledge regarding the role of MD1 in the regulation of cardiac pathophysiology.

C1-based biomanufacturing: Advances, challenges and perspectives.

One-carbon (C1) compounds have emerged as a key research focus due to the growth of metabolic engineering and synthetic biology as affordable and sustainable nonfood sugar feedstocks for energy-efficient and environmentally friendly biomanufacturing. This paper summarizes and discusses current developments in C1 compounds for biomanufacturing. First, two primary groups of microbes that use C1 compounds (native and synthetic) are introduced, and the traits, categorization, and functions of C1 microbes are summarized. Second, engineering strategies for C1 utilization are compiled and reviewed, including reconstruction of C1-utilization pathway, enzyme engineering, cofactor engineering, genome-scale modeling, and adaptive laboratory evolution. Third, a review of C1 compounds' uses in the synthesis of biofuels and high-value compounds is presented. Finally, potential obstacles to C1-based biomanufacturing are highlighted along with future research initiatives.