Inclisiran Treatment for Cardiovascular Disease Risk Reduction: A Systematic Review and Meta-Analysis.

This study was a meta-analysis of patient data to investigate the therapeutic effects of inclisiran on LDL-C, PCSK9, and TC in patients with atherosclerosis. Authors searched the Cochrane Library, Pubmed, EMBASE, and Web of Science databases for randomised controlled trials. Data of 4,731 subjects from five randomised clinical trials were included in this analysis. Patients treated with the PCSK9 inhibitor inclisiran had significantly lower LDL-C levels than those treated with placebo or a statin (mean difference (MD) -1.477; 95% CI -1.551 to -1.403; p <0.001; I2 = 7.2%). The average level of PCSK9 was also relatively lower ((MD) -2.579; 95% CI -2.694 to -2.464; p <0.001; I2 = 36%). They exhibited significant reductions in total cholesterol protein levels ((MD) -1.477; 95% CI -1.585 to -1.369; p <0.001; I2 = 46.7%). Inclisiran reduced LDL-C and PCSK9 levels as well as TC and Apo B levels significantly in patients with atherosclerotic cardiovascular disease (ASCVD). Key Words: Inclisiran, Low-density lipoprotein cholesterol, Atherosclerosis, Adverse events, Meta-analysis.

[Characterizations of soil enzyme activities and stoichiometry in three subtropical forest stands]. / äºšçƒ­å¸¦ä¸‰ç§æž—åˆ†åœŸå£¤é ¶æ´»æ€§å’Œé ¶åŒ–å­¦è®¡é‡æ¯”ç‰¹å¾.

We conducted in a common garden experiment to explore the differences in soil enzyme activity, stoichiometry, and their influencing factors among a secondary Castanopsis carlesii forest, 10-year-old C. carlesii plantation, and Cunninghamia lanceolata plantation. The results showed that compared to the secondary forest, the soil organic carbon, total nitrogen, and dissolved organic carbon significantly decreased by 42.6%, 47.4%, and 60.9% in C. carlesii plantation, and by 42.9%, 36.7%, and 61.1% in C. lanceolata plantation. Soil microbial biomass C, microbial biomass N (MBN), and microbial biomass phosphorus decreased significantly by 40.6%, 35.5%, and 45.9% in C. carlesii plantation, and by 53.7%、56.4%, and 61.7% in C. lanceolata plantation. Compared to the secondary forest, soil enzymes activities in C. carlesii plantation did not change significantly, but in C. lanceolata plantation, the activities of ß-1,4-glucosidase and cellobiohydrolase significantly decreased by 51.2% and 59.8%, ß-N-acetyl glucosaminidase and acid phosphatase decreased significantly by 41.0% and 29.8%, and enzymatic C:N acquisition ratio and enzymatic C:P acquisition ratio significantly decreased by 11.3% and 7.7%, respectively. Results of redundancy analysis indicated that MBN and NO3--N were the primary factors influencing soil enzyme activity and enzymic stoichiometry. Collectively, there were significant differences in soil enzyme activity and microbial nutrient demands among different forest stands. Compared to secondary forests, the establishment of C. lanceolata plantations would intensify nutrient competition between plants and microbes, and exacerbate the N and P limitations for microbes.

Application of 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging in recurrent anastomotic tumors after surgery in digestive tract tumors.

BACKGROUND: This study was to investigate the application value of whole-body dynamic 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging in recurrent anastomotic tumors of digestive tract after gastric and esophageal cancer surgery. Postoperative patients with gastric and esophageal cancer have a high risk of tumor recurrence, and traditional imaging methods have certain limitations in early detection of recurrent tumors. Whole-body dynamic 18F-FDG PET/CT imaging, due to its high sensitivity and specificity, can provide comprehensive information on tumor metabolic activity, which is expected to improve the early diagnosis rate of postoperative recurrent tumors, and provide an important reference for clinical treatment decision-making. AIM: To investigate the clinical value of whole-body dynamic 18F-FDG PET/CT imaging in differentiating anastomotic recurrence and inflammation after the operation of upper digestive tract tumors. METHODS: A retrospective analysis was performed on 53 patients with upper digestive tract tumors after operation and systemic dynamic 18F-FDG PET/CT imaging indicating abnormal FDG uptake by anastomosis, including 29 cases of gastric cancer and 24 cases of esophageal cancer. According to the follow-up results of gastroscopy and other imaging examinations before and after PET/CT examination, the patients were divided into an anastomotic recurrence group and anastomotic inflammation group. Patlak multi-parameter analysis software was used to obtain the metabolic rate (MRFDG), volume of distribution maximum (DVmax) of anastomotic lesions, and MRmean and DVmean of normal liver tissue. The lesion/background ratio (LBR) was calculated by dividing the MRFDG and DVmax of the anastomotic lesion by the MRmean and DVmean of the normal liver tissue, respectively, to obtain LBR-MRFDG and LBR-DVmax. An independent sample t test was used for statistical analysis, and a receiver operating characteristic curve was used to analyze the differential diagnostic efficacy of each parameter for anastomotic recurrence and inflammation. RESULTS: The dynamic 18F-FDG PET/CT imaging parameters MRFDG, DVmax, LBR-MRFDG, and LBR-DVmax of postoperative anastomotic lesions in gastric cancer and esophageal cancer showed statistically significant differences between the recurrence group and the inflammatory group (P < 0.05). The parameter LBR-MRFDG showed good diagnostic efficacy in differentiating anastomotic inflammation from recurrent lesions. In the gastric cancer group, the area under the curve (AUC) value was 0.935 (0.778, 0.993) when the threshold was 1.83, and in the esophageal cancer group, the AUC value was 1. When 86 is the threshold, the AUC value is 0.927 (0.743, 0.993). CONCLUSION: Whole-body dynamic 18F-FDG PET/CT imaging can accurately differentiate the diagnosis of postoperative anastomotic recurrence and inflammation of gastric cancer and esophageal cancer and has the potential to be an effective monitoring method for patients with upper digestive tract tumors after surgical treatment.

Mechanical Grinding-Induced Intermolecular Charge Transfer for Near-Infrared Photothermal Conversion.

In this study, charge-transfer-type compounds comprising synthesized naphthalenediimide derivative (H4NDISA) or its Pb-based coordination polymer (Pb-NDISA) and suitable primary or secondary amine organic molecules were prepared by the solvent-free mechanical grinding method. The coloration phenomenon arising from charge transfer during grinding serves as a discriminative tool for distinguishing various organic guest molecules. The porous structure of Pb-NDISA crystals facilitates the infiltration of guest molecules and contributes to the preservation of the intermolecular charge transfer state. Moreover, the intermolecular charge transfer induced by grinding exhibits remarkable stability in an ambient atmosphere, underscoring the pivotal role of well-ordered molecules in the mechanical grinding procedure. This mechanochromic phenomenon holds promise for the detection and sensing of organic molecules, while the exceptional charge-transfer absorption characteristics offer the potential for efficient near-infrared photothermal conversion.

Activation of α7 nicotinic acetylcholine receptors inhibits hepatic necroptosis and ameliorates acute liver injury in mice.

BACKGROUND: Acute liver injury (ALI) is a disease characterized by severe liver dysfunction, caused by significant infiltration of immune cells and extensive cell death with a high mortality. Previous studies demonstrated that the α7 nicotinic acetylcholine receptor (α7nAChR) played a crucial role in various liver diseases. The hypothesis of this study was that activating α7nAChR could alleviate ALI and investigate its possible mechanisms. METHODS: ALI was induced by intraperitoneal injection of lipopolysaccharide (LPS)/D-galactosamine (D-Gal) in wild type (WT), α7nAChR knockout (α7nAChR -/-) and Sting mutation (Stinggt/gt) mice in the presence or absence of a pharmacological selective α7nAChR agonist (PNU-282987). The effects of α7nAChR on hepatic injury, inflammatory response, mitochondrial damage, necroptosis and infiltration of immune cells during ALI were assessed. RESULTS: The expression of α7nAChR in liver tissue was increased in LPS/D-Gal induced ALI mice. Compared to the age-matched WT mice, α7nAChR deficiency decreased the survival rate, exacerbated the hepatic injury accompanied with enhanced inflammatory response and oxidative stress, and aggravated hepatic mitochondrial damage and necroptosis. Conversely, pharmacological activation of α7nAChR by PNU-282987 displayed the opposite trends. Furthermore, PNU-282987 significantly reduced the proportion of infiltrating monocyte-derived macrophages (CD45+CD11bhiF4/80int), M1 macrophages (CD45+CD11b+F4/80+CD86 hiCD163low), Ly6Chi monocytes (CD45+CD11b+MHCⅡ lowLy6C hi), but increased the resident Kupffer cells (CD45+CD11bintF4/80 hiTIM4 hi) in the damaged hepatic tissues caused by LPS/D-Gal. Interestingly, α7nAChR deficiency promoted the STING signaling pathway under LPS/D-Gal stimulation, while PNU-282987 treatment significantly prevented its activation. Finally, it was found that Sting mutation abolished the protective effects against hepatic injury by activating α7nAChR. CONCLUSIONS: Our study revealed that activating α7nAChR could protect against LPS/D-Gal induced ALI by inhibiting hepatic inflammation and necroptosis possibly via regulating immune cells infiltration and inhibiting STING signaling pathway.

Accuracy of cell-free Mycobacterium tuberculosis DNA testing in pleural effusion for diagnosing tuberculous pleurisy: a multicenter cross-sectional study.

BACKGROUND: The diagnosis of tuberculous pleurisy (TP) presents a significant challenge due to the low bacterial load in pleural effusion (PE) samples. Cell-free Mycobacterium tuberculosis DNA (cf-TB) in PE samples is considered an optimal biomarker for diagnosing TP. This study aimed to evaluate the applicability of cf-TB testing across diverse research sites with a relatively large sample size. METHODS: Patients suspected of TP and presenting with clinical symptoms and radiological evidence of PE were consecutively enrolled by treating physicians from 11 research sites across 6 provinces in China between April 2020 and August 2022. Following centrifugation, sediments obtained from PE were used for Xpert MTB/RIF (Xpert) and mycobacterial culture, while the supernatants were subjected to cf-TB testing. This study employed a composite reference standard to definite TP, which was characterized by any positive result for Mycobacterium tuberculosis (MTB) through either PE culture, PE Xpert, or pleural biopsy. RESULTS: A total of 1412 participants underwent screening, and 1344 (95.2%) were subsequently enrolled in this study. Data from 1241 (92.3%) participants were included, comprising 284 with definite TP, 677 with clinically diagnosed TP, and 280 without TP. The sensitivity of cf-TB testing in definite TP was 73.6% (95% CI 68.2-78.4), significantly higher than both Xpert (40.8%, 95% CI 35.3-46.7, P < 0.001) and mycobacterial culture (54.2%, 95% CI 48.4-59.9, P < 0.001). When clinically diagnosed TP was incorporated into the composite reference standard for sensitivity analysis, cf-TB testing showed a sensitivity of 46.8% (450/961, 95% CI 43.7-50.0), significantly higher than both Xpert (116/961, 12.1%, 95% CI 10.2-14.3, P < 0.001) and mycobacterial culture (154/961, 16.0%, 95% CI 13.8-18.5, P < 0.001). The specificities of cf-TB testing, Xpert, and mycobacterial culture were all 100.0%. CONCLUSIONS: The performance of cf-TB testing is significantly superior to that of Xpert and mycobacterial culture methods, indicating that it can be considered as the primary diagnostic approach for improving TP detection. Trial registration The trial was registered on Chictr.org.cn (ChiCTR2000031680, https://www.chictr.org.cn/showproj.html?proj=49316 ).

Photochemical [2 + 2] Cycloaddition Enables the Synthesis of Highly Thermally Stable and Acid/Base-Resistant Polyesters from a Nonpolymerizable α,ß-Conjugated Valerolactone.

We report a simple strategy to transform a nonpolymerizable six-membered α,ß-conjugated lactone, 5,6-dihydro-2H-pyran-2-one (DPO), into polymerizable bicyclic lactones via photochemical [2 + 2] cycloaddition. Two bicyclic lactones, M1 and M2, were obtained by the photochemical [2 + 2] cycloaddition of tetramethylethylene and DPO. Ring-opening polymerization (ROP) of M1 and M2 catalyzed by diphenyl phosphate (DPP), La[N(SiMe3)2]3, and 1-tert-butyl-4,4,4-tris(dimethylamino)-2,2-bis[tris (dimethylamino) phosphoranylide-namino]-2λ5, 4λ5-catenadi(phosphazene) (tBu-P4) were conducted. M1 is highly polymerizable, either DPP or La[N(SiMe3)2]3 could catalyze its living ROP under mild conditions, affording the well-defined PM1 with a predictable molar mass and low dispersity. M2 could only be polymerized with tBu-P4 as the catalyst, also generating the same polymer PM1. PM1 has high thermal stability, with a Td,5% being up to 376 °C. Ring-opening copolymerization (ROcP) of M1 and δ-valerolactone (δ-VL) catalyzed by La[N(SiMe3)2]3 afforded a series of random copolymers with enhanced thermal stabilities. Both PM1 and the copolymer containing 10 mol % M1 exhibited excellent resistance to acidic and basic hydrolysis. Our results demonstrate that direct photochemical [2 + 2] cycloaddition of α,ß-conjugated valerolactone is not only a strategy to tune its polymerizability, but also allows for the synthesis of highly thermally stable aliphatic polyesters, inaccessible by other methods.

Simulated human digestion and fermentation of a high-molecular weight polysaccharide from Lentinula edodes mushroom and protective effects on intestinal barrier.

Lentinula edodes (Shiitake) is an important edible mushroom and polysaccharides are its major constituents with proven health benefits. The study was to investigate the gut bacterial fermentation and subsequent effects on gut barrier function of a glucan-rich polysaccharide, LePS40 precipitated from the mushroom water extract with 40 % (v/v) ethanol. LePS40 consisted of a ß-(1→3)-glucan main chain with substitution in the C-6 position with side chains mainly composed of (1 → 6)-linked ß-Glcp residues, (1 → 6)-linked α-Galp residues and terminal residues of ß-Glcp. LePS40 was found highly resistant to digestive enzymes and gastric acid in simulated human gastrointestinal tract, but highly fermentable during in vitro human fecal fermentation. The fecal fermentation degradation of LePS40 appeared to selectively break the glucoside linkage in view of the dramatic decrease in the glucose molar ratio (12.68 to 1.07). Compared with the prebiotic reference FOS, LePS40 led to much higher levels of butyric, and propionic acid and a lower level of acetic acid. Moreover, LePS40 enhanced the abundance of some beneficial bacterial populations, but decreased the bacteria possibly linked with fatty-liver disease and colorectal cancer. Furthermore, the fecal fermentation products of LePS40 showed a potential protective effect on intestinal barrier function against inflammatory damage in Caco-2/Raw264.7 co-culture model. These findings suggest the potential of LePS40 for improvement of gut health through modulation of gut microbiota.

How health seeking behavior develops in patients with type 2 diabetes: a qualitative study based on health belief model in China.

Background: Type 2 diabetes(T2DM) is a global health problem which is accompanied with multi-systemic complications, and associated with long-term health burden and economic burden. Effective health seeking behavior (HSB) refers to reasonably utilize health resources, effectively prevent and treat diseases, and maintain health. Effective health seeking behavior (HSB) is vital to mitigate the risk of T2DM complications. However, health seeking behavior for T2DM patients remains sub-optimal worldwide. Objective: The study aimed to explore the internal logic of how health seeking behavior of T2DM patients develops and the influencing factors of health seeking behavior. With a view to provide a reference basis for improving the health seeking behavior situation of T2DM patients. Methods: This study was conducted at an integrated tertiary hospital in China. People who were diagnosed with T2DM, capable of expressing clearly and had no mental illness, were approached based on a purposive sampling. The experience of T2DM and health seeking behavior were collected via in-depth interviews. A theory-driven thematic analysis based on Health Belief Model (HBM) was applied for data analysis. Inductive reasoning was used to identify emerging themes which were not included in HBM. Results: 26 patients with T2DM were included in the current study. Seven themes were identified, including: (1) T2DM diagnosis and severity; (2) T2DM treatment and management; (3) Perceived susceptibility of diabetes progression; (4) Perceived severity of diabetes progression; (5) Perceived benefits of health seeking behavior; (6) Perceived barriers of health seeking behavior; (7) Perception of behavioral cues. Generally, patients with T2DM lacked reliable sources of information, considered T2DM to be slow-progressing and without posing an immediate threat to life. Consequently, they did not fully grasp the long-term risks associated with T2DM or the protective effects of health seeking behavior. Conclusion: This study highlighted the challenges in health seeking behavior for patients with T2DM. It suggested that future interventions and strategies should involve multi-faceted approaches, targeting healthcare providers (HCPs), patients with T2DM, and their support networks. This comprehensive strategy can help patients better understand their condition and the importance of effective health seeking behavior. Ultimately, enhancing their capacity for adopting appropriate health-seeking practices.

A few-shot identification method for stochastic dynamical systems based on residual multipeaks adaptive sampling.

Neural networks are popular data-driven modeling tools that come with high data collection costs. This paper proposes a residual-based multipeaks adaptive sampling (RMAS) algorithm, which can reduce the demand for a large number of samples in the identification of stochastic dynamical systems. Compared to classical residual-based sampling algorithms, the RMAS algorithm achieves higher system identification accuracy without relying on any hyperparameters. Subsequently, combining the RMAS algorithm and neural network, a few-shot identification (FSI) method for stochastic dynamical systems is proposed, which is applied to the identification of a vegetation biomass change model and the Rayleigh-Van der Pol impact vibration model. We show that the RMAS algorithm modifies residual-based sampling algorithms and, in particular, reduces the system identification error by 76% with the same sample sizes. Moreover, the surrogate model accurately predicts the first escape probability density function and the P bifurcation behavior in the systems, with the error of less than 1.59×10-2. Finally, the robustness of the FSI method is validated.

Entropic stochastic resonance of finite-size particles in confined Brownian transport.

We demonstrate the existence of entropic stochastic resonance (ESR) of passive Brownian particles with finite size in a double- or triple-circular confined cavity, and compare the similarities and differences of ESR in the double-circular cavity and triple-circular cavity. When the diffusion of Brownian particles is constrained to the double- or triple-circular cavity, the presence of irregular boundaries leads to entropic barriers. The interplay between the entropic barriers, a periodic input signal, the gravity of particles, and intrinsic thermal noise may give rise to a peak in the spectral amplification factor and therefore to the appearance of the ESR phenomenon. It is shown that ESR can occur in both a double-circular cavity and a triple-circular cavity, and by adjusting some parameters of the system, the response of the system can be optimized. The differences are that the spectral amplification factor in a triple-circular cavity is significantly larger than that in a double-circular cavity, and compared with the ESR in a double-circular cavity, the ESR effect in a triple-circular cavity occurs within a wider range of external force parameters. In addition, the strength of ESR also depends on the particle radius, and smaller particles can induce more obvious ESR, indicating that the size effect cannot be safely neglected. The ESR phenomenon usually occurs in small-scale systems where confinement and noise play an important role. Therefore, the mechanism that is found could be used to manipulate and control nanodevices and biomolecules.

Prognostic value of the Naples prognostic score in patients with intrahepatic cholangiocarcinoma after hepatectomy.

BACKGROUND: The Naples Prognostic Score (NPS), integrating inflammatory and nutritional biomarkers, has been reported to be associated with the prognosis of various malignancies, but there is no report on intrahepatic cholangiocarcinoma (ICC). This study aimed to explore the prognostic value of NPS in patients with ICC. METHODS: Patients with ICC after hepatectomy were collected, and divided into three groups. The prognosis factors were determined by Cox regression analysis. Predictive efficacy was evaluated by the time-dependent receiver operating characteristic (ROC) curves. RESULTS: A total of 174 patients were included (Group 1: 33 (19.0%) patients; Group 2: 83 (47.7%) patients; and Group 3: 58 (33.3%) patients). The baseline characteristics showed the higher the NPS, the higher the proportion of patients with cirrhosis and Child-Pugh B, and more advanced tumors. The Kaplan-Meier curves reflect higher NPS were associated with poor survival. Multivariable analysis showed NPS was an independent risk factor of overall survival (NPS group 2 vs. 1: HR = 1.671, 95% CI: 1.022-3.027, p = 0.009; NPS group 3 vs. 1: HR = 2.208, 95% CI: 1.259-4.780, p = 0.007) and recurrence-free survival (NPS group 2 vs. 1: HR = 1.506, 95% CI: 1.184-3.498, p = 0.010; NPS group 3 vs. 1: HR = 2.141, 95% CI: 2.519-4.087, P = 0.001). The time ROC indicated NPS was superior to other models in predicting prognosis. CONCLUSIONS: NPS is a simple and effective tool for predicting the long-term survival of patients with ICC after hepatectomy. Patients with high NPS require close follow-up, and improving NPS may prolong the survival time.

Thermally Stable and Chemically Recyclable Poly(ketal-ester)s Regulated by Floor Temperature.

Chemical recycling to monomers (CRM) offers a promising closed-loop approach to transition from current linear plastic economy toward a more sustainable circular paradigm. Typically, this approach has focused on modulating the ceiling temperature (Tc) of monomers. Despite considerable advancements, polymers with low Tc often face challenges such as inadequate thermal stability, exemplified by poly(γ-butyrolactone) (PGBL) with a decomposition temperature of ∼200 °C. In contrast, floor temperature (Tf)-regulated polymers, particularly those synthesized via the ring-opening polymerization (ROP) of macrolactones, inherently exhibit enhanced thermodynamic stability as the temperature increases. However, the development of those Tf regulated chemically recyclable polymers remains relatively underexplored. In this context, by judicious design and efficient synthesis of a biobased macrocyclic diester monomer (HOD), we developed a type of Tf -regulated closed-loop chemically recyclable poly(ketal-ester) (PHOD). First, the entropy-driven ROP of HOD generated high-molar mass PHOD with exceptional thermal stability with a Td,5% reaching up to 353 °C. Notably, it maintains a high Td,5% of 345 °C even without removing the polymerization catalyst. This contrasts markedly with PGBL, which spontaneously depolymerizes back to the monomer above its Tc in the presence of catalyst. Second, PHOD displays outstanding closed-loop chemical recyclability at room temperature within just 1 min with tBuOK. Finally, copolymerization of pentadecanolide (PDL) with HOD generated high-performance copolymers (PHOD-co-PPDL) with tunable mechanical properties and chemical recyclability of both components.

A qualitative study on inner experience of self-management behavior among elderly patients with type 2 diabetes in rural areas.

BACKGROUND: As a chronic metabolic disease, diabetes poses a serious threat to human health and has become a major public health problem in China and worldwide. In 2020, 30% of Chinese people (aged ≥ 60 years) reported having diabetes mellitus. Moreover, individuals with diabetes living in rural areas face a significantly higher mortality risk compared to those in urban areas. In this study, we explored the inner experience of self-management behaviors in elderly patients with type 2 diabetes in rural areas to inform targeted interventions. METHODS: A phenomenological research design was used to explore the inner experience of self-management in rural elderly diabetes. Ten elderly diabetic patients were sampled from December 2022 to March 2023 in rural areas of Yangcheng County, Jincheng City, ShanXi Province, China. The seven-step Colaizzi phenomenological was used to analyze the interview data and generate themes. RESULTS: Four themes emerged: "Insufficient self-management cognition", "Negative self-management attitude", "Slack self-management behavior", and "No time for self-management". CONCLUSION: The level of self-management among elderly patients with type 2 diabetes in rural areas is low. Healthcare professionals should develop targeted interventions aimed at enhancing their cognitive levels, modifying their coping styles, and improving their self-management abilities to improve their quality of life.

Suppression of photoreactivation of E. coli by excimer far-UV light (222 nm) via damage to multiple targets.

Low-pressure mercury lamps emitting at 254 nm (UV254) are used widely for disinfection. However, subsequent exposure to visible light results in photoreactivation of treated bacteria. This study employed a krypton chloride excimer lamp emitting at 222 nm (UV222) to inactivate E. coli. UV222 and UV254 treatment had similar E. coli-inactivation kinetics. Upon subsequent irradiation with visible light, E. coli inactivated by UV254 was reactivated from 2.71-log to 4.75-log, whereas E. coli inactivated by UV222 showed negligible photoreactivation. UV222 treatment irreversibly broke DNA strands in the bacterium, whereas UV254 treatment primarily formed nucleobase dimers. Additionally, UV222 treatment caused cell membrane damage, resulting in wizened, pitted cells and permeability changes. The damage to the cell membrane was mainly due to the photolysis of proteins and lipids by UV222. Furthermore, the photolysis of proteins by UV222 destroyed enzymes, which blocked photoreactivation and dark repair. The multiple damages can be further evidenced by 4.0-61.1 times higher quantum yield in the photolysis of nucleobases and amino acids for UV222 than UV254. This study demonstrates that UV222 treatment damages multiple sites in bacteria, leading to their inactivation. Employing UV222 treatment as an alternative to UV254 could be viable for inhibiting microorganism photoreactivation in water and wastewater.

Identification of Key lncRNAs in Gout Under Copper Death and Iron Death Mechanisms: A Study Based on ceRNA Network Analysis and Random Forest Algorithm.

This study focused on identifying potential key lncRNAs associated with gout under the mechanisms of copper death and iron death through ceRNA network analysis and Random Forest (RF) algorithm, which aimed to provide new insights into the molecular mechanisms of gout, and potential molecular targets for future therapeutic strategies of gout. Initially, we conducted an in-depth bioinformatics analysis of gout microarray chips to screen the key cuproptosis-related genes (CRGs) and key ferroptosis-related genes (FRGs). Using these data, we constructed a key ceRNA network for gout. Finally, key lncRNAs associated with gout were identified through the RF algorithm combined with ROC curves, and validated using the Comparative Toxicogenomics Database (CTD). We successfully identified NLRP3, LIPT1, and DBT as key CRGs associated with gout, and G6PD, PRKAA1, LIG3, PHF21A, KLF2, PGRMC1, JUN, PANX2, and AR as key FRGs associated with gout. The key ceRNA network identified four downregulated key lncRNAs (SEPSECS-AS1, LINC01054, REV3L-IT1, and ZNF883) along with three downregulated mRNAs (DBT, AR, and PRKAA1) based on the ceRNA theory. According to CTD validation inference scores and biological functions of target mRNAs, we identified a potential gout-associated lncRNA ZNF883/hsa-miR-539-5p/PRKAA1 regulatory axis. This study identified the key lncRNA ZNF883 in the context of copper death and iron death mechanisms related to gout for the first time through the application of ceRNA network analysis and the RF algorithm, thereby filling a research gap in this field and providing new insights into the molecular mechanisms of gout. We further found that lncRNA ZNF883 might function in gout patients by regulating PRKAA1, the mechanism of which was potentially related to uric acid reabsorption in the proximal renal tubules and inflammation regulation. The proposed lncRNA ZNF883/hsa-miR-539-5p/PRKAA1 regulatory axis might represent a potential RNA regulatory pathway for controlling the progression of gout disease. This discovery offered new molecular targets for the treatment of gout, and had significant implications for future therapeutic strategies in managing the gout.

Deep learning using contrast-enhanced ultrasound images to predict the nuclear grade of clear cell renal cell carcinoma.

PURPOSE: To assess the effectiveness of a deep learning model using contrastenhanced ultrasound (CEUS) images in distinguishing between low-grade (grade I and II) and high-grade (grade III and IV) clear cell renal cell carcinoma (ccRCC). METHODS: A retrospective study was conducted using CEUS images of 177 Fuhrmangraded ccRCCs (93 low-grade and 84 high-grade) from May 2017 to December 2020. A total of 6412 CEUS images were captured from the videos and normalized for subsequent analysis. A deep learning model using the RepVGG architecture was proposed to differentiate between low-grade and high-grade ccRCC. The model's performance was evaluated based on sensitivity, specificity, positive predictive value, negative predictive value and area under the receiver operating characteristic curve (AUC). Class activation mapping (CAM) was used to visualize the specific areas that contribute to the model's predictions. RESULTS: For discriminating high-grade ccRCC from low-grade, the deep learning model achieved a sensitivity of 74.8%, specificity of 79.1%, accuracy of 77.0%, and an AUC of 0.852 in the test set. CONCLUSION: The deep learning model based on CEUS images can accurately differentiate between low-grade and high-grade ccRCC in a non-invasive manner.

Enabling Closed-Loop Circularity of "Non-Polymerizable" α, ß-Conjugated Lactone Towards High-Performance Polyester with the Assistance of Cyclopentadiene.

Chemical recycling of polymers to monomers presents a promising solution to the escalating crisis associated with plastic waste. Despite considerable progress made in this field, the primary efforts have been focused on redesigning new monomers to produce readily recyclable polymers. In contrast, limited research into the potential of seemingly "non-polymerizable" monomers has been conducted. Herein, we propose a paradigm that leverages a "chaperone"-assisted strategy to establish closed-loop circularity for a "non-polymerizable" α, ß-conjugated lactone, 5,6-dihydro-2H-pyran-2-one (DPO). The resulting PDPO, a structural analogue of poly(δ-valerolactone) (PVL), exhibits enhanced thermal properties with a melting point (Tm) of 114 °C and a decomposition temperature (Td,5%) of 305 °C. Notably, owing to the structural similarity between DPO and δ-VL, the copolymerization generates semi-crystalline P(DPO-co-VL)s irrespective of the DPO incorporation ratio. Intriguingly, the inherent C=C bonds in P(DPO-co-VL)s enable their convenient post-functionalization via Michael-addition reaction. Lastly, PDPO was demonstrated to be chemically recyclable via ring-closing metathesis (RCM), representing a significant step towards the pursuit of enabling the closed-loop circularity of "non-polymerizable" lactones without altering the ultimate polymer structure.

Photothermal Conversion Perylene-Based Metal-Organic Framework with Panchromatic Absorption Bandwidth across the Visible to Near-Infrared.

Recently, facilely designable metal-organic frameworks have gained attention in the construction of photothermal conversion materials. Nonetheless, most of the previously reported photothermal conversion metal-organic frameworks exhibit limited light absorption capabilities. In this work, a distinctive metal-organic framework with heterogeneous periodic alternate spatial arrangements of metal-oxygen clusters and perylene-based derivative molecules was prepared by in situ synthesis. The building blocks in this inimitable structure behave as both electron donors and electron acceptors, giving rise to the significant inherent charge transfer in this crystalline material, resulting in a narrow band gap with excellent panchromatic absorption, with the ground state being the charge transfer state. Moreover, it can retain excellent air-, photo-, and water-stability in the solid state. The excellent stability and broad light absorption characteristics enable the effective realization of near-infrared (NIR) photothermal conversion, including infrequent NIR-II photothermal conversion, in this perylene-based metal-organic framework.

Bioinformatics Analysis and Experimental Validation of Differential Genes and Pathways in Bone Nonunions.

Non-union fractures pose a significant clinical challenge, often leading to prolonged pain and disability. Understanding the molecular mechanisms underlying non-union fractures is crucial for developing effective therapeutic interventions. This study integrates bioinformatics analysis and experimental validation to unravel key genes and pathways associated with non-union fractures. We identified differentially expressed genes (DEGs) between non-union and fracture healing tissues using bioinformatics techniques. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were employed to elucidate the biological processes and pathways involved. Common DEGs were identified, and a protein-protein interaction (PPI) network was constructed. Fibronectin-1 (FN1), Thrombospondin-1 (THBS1), and Biglycan (BGN) were pinpointed as critical target genes for non-union fracture treatment. Experimental validation involved alkaline phosphatase (ALP) and Alizarin Red staining to confirm osteogenic differentiation. Our analysis revealed significant alterations in pathways related to cell behavior, tissue regeneration, wound healing, infection, and immune responses in non-union fracture tissues. FN1, THBS1, and BGN were identified as key genes, with their upregulation indicating potential disruptions in the bone remodeling process. Experimental validation confirmed the induction of osteogenic differentiation. The study provides comprehensive insights into the molecular mechanisms of non-union fractures, emphasizing the pivotal roles of FN1, THBS1, and BGN in extracellular matrix dynamics and bone regeneration. The findings highlight potential therapeutic targets and pathways for further investigation. Future research should explore interactions between these genes, validate results using in vivo fracture models, and develop tailored treatment strategies for non-union fractures, promising significant advances in clinical management.