Nutrient-Sensitive Reinforcement Learning in Monkeys.

In reinforcement learning (RL), animals choose by assigning values to options and learn by updating these values from reward outcomes. This framework has been instrumental in identifying fundamental learning variables and their neuronal implementations. However, canonical RL models do not explain how reward values are constructed from biologically critical intrinsic reward components, such as nutrients. From an ecological perspective, animals should adapt their foraging choices in dynamic environments to acquire nutrients that are essential for survival. Here, to advance the biological and ecological validity of RL models, we investigated how (male) monkeys adapt their choices to obtain preferred nutrient rewards under varying reward probabilities. We found that the nutrient composition of rewards strongly influenced learning and choices. Preferences of the animals for specific nutrients (sugar, fat) affected how they adapted to changing reward probabilities; the history of recent rewards influenced choices of the monkeys more strongly if these rewards contained the their preferred nutrients (nutrient-specific reward history). The monkeys also chose preferred nutrients even when they were associated with lower reward probability. A nutrient-sensitive RL model captured these processes; it updated the values of individual sugar and fat components of expected rewards based on experience and integrated them into subjective values that explained the choices of the monkeys. Nutrient-specific reward prediction errors guided this value-updating process. Our results identify nutrients as important reward components that guide learning and choice by influencing the subjective value of choice options. Extending RL models with nutrient-value functions may enhance their biological validity and uncover nutrient-specific learning and decision variables.SIGNIFICANCE STATEMENT RL is an influential framework that formalizes how animals learn from experienced rewards. Although reward is a foundational concept in RL theory, canonical RL models cannot explain how learning depends on specific reward properties, such as nutrients. Intuitively, learning should be sensitive to the nutrient components of the reward to benefit health and survival. Here, we show that the nutrient (fat, sugar) composition of rewards affects how the monkeys choose and learn in an RL paradigm and that key learning variables including reward history and reward prediction error should be modified with nutrient-specific components to account for the choice behavior observed in the monkeys. By incorporating biologically critical nutrient rewards into the RL framework, our findings help advance the ecological validity of RL models.

A Neural Mechanism in the Human Orbitofrontal Cortex for Preferring High-Fat Foods Based on Oral Texture.

Although overconsumption of high-fat foods is a major driver of weight gain, the neural mechanisms that link the oral sensory properties of dietary fat to reward valuation and eating behavior remain unclear. Here we combine novel food-engineering approaches with functional neuroimaging to show that the human orbitofrontal cortex (OFC) translates oral sensations evoked by high-fat foods into subjective economic valuations that guide eating behavior. Male and female volunteers sampled and evaluated nutrient-controlled liquid foods that varied in fat and sugar ("milkshakes"). During oral food processing, OFC activity encoded a specific oral-sensory parameter that mediated the influence of the foods' fat content on reward value: the coefficient of sliding friction. Specifically, OFC responses to foods in the mouth reflected the smooth, oily texture (i.e., mouthfeel) produced by fatty liquids on oral surfaces. Distinct activity patterns in OFC encoded the economic values associated with particular foods, which reflected the subjective integration of sliding friction with other food properties (sugar, fat, viscosity). Critically, neural sensitivity of OFC to oral texture predicted individuals' fat preferences in a naturalistic eating test: individuals whose OFC was more sensitive to fat-related oral texture consumed more fat during ad libitum eating. Our findings suggest that reward systems of the human brain sense dietary fat from oral sliding friction, a mechanical food parameter that likely governs our daily eating experiences by mediating interactions between foods and oral surfaces. These findings identify a specific role for the human OFC in evaluating oral food textures to mediate preference for high-fat foods.SIGNIFICANCE STATEMENT Fat and sugar enhance the reward value of food by imparting a sweet taste and rich mouthfeel but also contribute to overeating and obesity. Here we used a novel food-engineering approach to realistically quantify the physical-mechanical properties of high-fat liquid foods on oral surfaces and used functional neuroimaging while volunteers sampled these foods and placed monetary bids to consume them. We found that a specific area of the brain's reward system, the orbitofrontal cortex, detects the smooth texture of fatty foods in the mouth and links these sensory inputs to economic valuations that guide eating behavior. These findings can inform the design of low-calorie fat-replacement foods that mimic the impact of dietary fat on oral surfaces and neural reward systems.

Effects of non-pharmacological interventions for adults with subjective cognitive decline: a network meta-analysis and component network meta-analysis.

BACKGROUND: Non-pharmacological interventions have a myriad of available intervention options and contain multiple components. Whether specific components of non-pharmacological interventions or combinations are superior to others remains unclear. The main aim of this study is to compare the effects of different combinations of non-pharmacological interventions and their specific components on health-related outcomes in adults with subjective cognitive decline. METHODS: PubMed, Embase, Cochrane, CINAHL, PsycINFO, CENTRAL, Web of Science, and China's two largest databases, CNKI and Wanfang, were searched from inception to 22nd, January 2023. Randomized controlled trials using non-pharmacological interventions and reporting health outcomes in adults with subjective cognitive decline were included. Two independent reviewers screened studies, extracted data, and assessed risk of bias. Component network meta-analysis was conducted employing an additive component model for network meta-analysis. This study followed the PRISMA reporting guideline and the PRISMA checklist is presented in Additional file 2. RESULTS: A total of 39 trials with 2959 patients were included (range of mean ages, 58.79-77.41 years). Resistance exercise might be the optimal intervention for reducing memory complaints in adults with subjective cognitive decline; the surface under the cumulative ranking p score was 0.888, followed by balance exercise (p = 0.859), aerobic exercise (p = 0.832), and cognitive interventions (p = 0.618). Music therapy, cognitive training, transcranial direct current stimulation, mindfulness therapy, and balance exercises might be the most effective intervention components for improving global cognitive function (iSMD, 0.83; 95% CI, 0.36 to 1.29), language (iSMD, 0.31; 95% CI, 0.24 to 0.38), ability to perform activities of daily living (iSMD, 0.55; 95% CI, 0.21 to 0.89), physical health (iSMD, 3.29; 95% CI, 2.57 to 4.00), and anxiety relief (iSMD, 0.71; 95% CI, 0.26 to 1.16), respectively. CONCLUSIONS: The form of physical activity performed appears to be more beneficial than cognitive interventions in reducing subjective memory complaints for adults with subjective cognitive decline, and this difference was reflected in resistance, aerobic, and balance exercises. Randomized clinical trials with high-quality and large-scale are warranted to validate the findings. TRIAL REGISTRATION: PROSPERO registry number. CRD42022355363.

Defect Engineering in a Nanoporous Thulium-Organic Framework in Catalyzing Knoevenagel Condensation and Chemical CO2 Fixation.

Defect engineering is an extremely effective strategy for modifying metal-organic frameworks (MOFs), which can break through the application limitations of traditional MOFs and enhance their functionality. Herein, we report a highly robust nanoporous thulium(III)-organic framework, {[Tm2(BDCP)(H2O)5](NO3)·3DMF·2H2O}n (NUC-105), with [Tm(COO)2(H2O)]n chains and [Tm2(COO)4(H2O)8] dinuclears as metal nodes and 2,6-bis(2,4-dicarboxylphenyl)-4-(4-carboxylphenyl)pyridine (BDCP) linkers. In NUC-105, each of the four chains of [Tm(COO)2]n and the two rows of [Tm2(COO)4(H2O)8] units is unified by the organic skeleton, resulting in a rectangular nanochannel with dimensions of 15.35 Å × 11.29 Å, which leads to a void volume of 50%. It is worth mentioning that the [Tm2(COO)4(H2O)8] cluster is very rare in terms of its higher level of associated water molecules, implying that the activated host framework can serve as a strong Lewis acid. NUC-105a exhibited great heterogeneous catalytic performance for CO2 cycloaddition with epoxides under the reaction conditions (0.60 mol % NUC-105a, 5.0 mol % n-Bu4NBr, 65 °C, 5 h), ensuring exclusive selectivity and high conversion rates. In addition, NUC-105a's strong catalytic impact on the Knoevenagel condensation of aldehydes and malononitrile can be attributed to the collaboration between the drastically unsaturated Lewis acidic Tm3+ centers and Lewis basic pyridine groups.

Construction of platelet count-optical method reflex test rules using Micro-RBC#, Macro-RBC%, "PLT clumps?" flag, and "PLT abnormal histogram" flag on the Mindray BC-6800plus hematology analyzer in clinical practice.

OBJECTIVES: Utilizing RBC or PLT-related parameters to establish rules for the PLT-O reflex test can assist laboratories in quickly identifying specimens with interfered PLT-I that require PLT-O retesting. METHODS: Prospective PLT-I and PLT-O testing was performed on 6857 EDTA-anticoagulated whole blood samples, split randomly into training and validation cohorts at a 2:3 ratio. Reflex and non-reflex groups were distinguished based on the differences between PLT-I and PLT-O results. By comparing RBC and PLT parameter differences and flags in the training set, we pinpointed factors linked to PLT-O reflex testing. Utilizing Lasso regression, then refining through univariate and multivariate logistic regression, candidate parameters were selected. A predictive nomogram was constructed from these parameters and subsequently validated using the validation set. ROC curves were also plotted. RESULTS: Significant differences were observed between the reflex and non-reflex groups for 19 parameters including RBC, MCV, MCH, MCHC, RDW-CV, RDW-SD, Micro-RBC#, Micro-RBC%, Macro-RBC#, Macro-RBC%, MPV, PCT, P-LCC, P-LCR, PLR,"PLT clumps?" flag, "PLT abnormal histogram" flag, "IDA Anemia?" flag, and "RBC abnormal histogram" flag. After further analysis, Micro-RBC#, Macro-RBC%,"PLT clumps?", and "PLT abnormal histogram" flag were identified as candidate parameters to develop a nomogram with an AUC of 0.636 (95 %CI: 0.622-0.650), sensitivity of 42.9 % (95 %CI: 37.8-48.1 %), and specificity of 90.5 % (95 %C1: 89.6-91.3 %). CONCLUSIONS: The established rules may help laboratories improve efficiency and increase accuracy in determining platelet counts as a supplement to ICSH41 guidelines.

Dysregulation of AMPK-mTOR signaling leads to comorbid anxiety in Dip2a KO mice.

Autism is often comorbid with other psychiatric disorders. We have previously shown that Dip2a knockout (KO) induces autism-like behaviors in mice. However, the role of Dip2a in other psychiatric disorders remains unclear. In this paper, we revealed that Dip2a KO mice had comorbid anxiety. Dip2a KO led to a reduction in the dendritic length of cortical and hippocampal excitatory neurons. Molecular mechanism studies suggested that AMPK was overactivated and suppressed the mTOR cascade, contributing to defects in dendritic morphology. Deletion of Dip2a in adult-born hippocampal neurons (Dip2a conditional knockout (cKO)) increased susceptibility to anxiety upon acute stress exposure. Application of (2R,6R)-hydroxynorketamine (HNK), an inhibitor of mTOR, rescued anxiety-like behaviors in Dip2a KO and Dip2a cKO mice. In addition, 6 weeks of high-fat diet intake alleviated AMPK-mTOR signaling and attenuated the severity of anxiety in both Dip2a KO mice and Dip2a cKO mice. Taken together, these results reveal an unrecognized function of DIP2A in anxiety pathophysiology via regulation of AMPK-mTOR signaling.

Biomaterial-enabled therapeutic modulation of cGAS-STING signaling for enhancing antitumor immunity.

cGAS-STING signaling is a central component in the therapeutic action of most existing cancer therapies. The accumulated knowledge of tumor immunoregulatory network in recent years has spurred the development of cGAS-STING agonists for tumor treatment as an effective immunotherapeutic strategy. However, the clinical translation of these agonists is thus far unsatisfactory because of the low immunostimulatory efficacy and unrestricted side effects under clinically relevant conditions. Interestingly, the rational integration of biomaterial technology offers a promising approach to overcome these limitations for more effective and safer cGAS-STING-mediated tumor therapy. Herein, we first outline the cGAS-STING signaling axis and generally discuss its association with tumors. We then symmetrically summarize the recent progress in those biomaterial-based cGAS-STING agonism strategies to generate robust antitumor immunity, categorized by the chemical nature of those cGAS-STING stimulants and carrier substrates. Finally, a perspective is provided to discuss the existing challenges and potential opportunities in cGAS-STING modulation for tumor therapy.

Defect-engineered indium-organic framework displays the higher CO2 adsorption and more excellent catalytic performance on the cycloaddition of CO2 with epoxides under mild conditions.

In order to achieve the high adsorption and catalytic performance of CO2, the direct self-assembly of robust defect-engineered MOFs is a scarcely reported and challenging proposition. Herein, a highly robust nanoporous indium(III)-organic framework of {[In2(CPPDA)(H2O)3](NO3)·2DMF·3H2O}n (NUC-107) consisting of two kinds of inorganic units of chain-shaped [In(COO)2(H2O)]n and watery binuclear [In2(COO)4(H2O)8] was generated by regulating the growth environment. It is worth mentioning that [In2(COO)4(H2O)8] is very rare in terms of its richer associated water molecules, implying that defect-enriched metal ions in the activated host framework can serve as strong Lewis acid. Compared to reported skeleton of [In4(CPPDA)2(µ3-OH)2(DMF)(H2O)2]n (NUC-66) with tetranuclear clusters of [In4(µ3-OH)2(COO)10(DMF)(H2O)2] as nodes, the void volume of NUC-107 (50.7%) is slightly lower than the one of NUC-66 (52.8%). However, each In3+ ion in NUC-107 has an average of 1.5 coordinated small molecules (H2O), which far exceeds the average of 0.75 in NUC-66 (H2O and DMF). After thermal activation, NUC-107a characterizes the merits of unsaturated In3+ sites, free pyridine moieties, solvent-free nanochannels (10.2 × 15.7 Å2). Adsorption tests prove that the host framework of NUC-107a has a higher CO2 adsorption (113.2 cm3/g at 273 K and 64.8 cm3/g at 298 K) than NUC-66 (91.2 cm3/g at 273 K and 53.0 cm3/g at 298 K). Catalytic experiments confirmed that activated NUC-107a with the aid of n-Bu4NBr was capable of efficiently catalyzing the cycloaddition of CO2 with epoxides into corresponding cyclic carbonates under the mild conditions. Under the similar conditions of 0.10 mol% MOFs, 0.5 mol% n-Bu4NBr, 0.5 MP CO2, 60 °C and 3 h, compared with NUC-66a, the conversion of SO to SC catalyzed by NUC-107a increased by 21%. Hence, this work offers a valuable perspective that the in situ creation of robust defect-engineered MOFs can be realized by regulating the growth environment.

Physical frailty intensifies the positive association of oral frailty with poor global cognitive function and executive function among older adults especially for females: a cross-sectional study.

BACKGROUND: Oral frailty is reported to increase the risk of new onset of mild cognitive impairment. Whereas, the association of oral frailty with cognition among older adults in both physical frail and non-physical frail status has not been sufficiently explored, and whether there are sex differences in the association is unclear. This study investigated the association of oral frailty and physical frailty with global cognitive function and executive function among older adults, as well as the sex differences in such association. METHODS: This cross-sectional study included 307 participants aged ≥ 60 years old from communities between June 2023 and August 2023, in Nanjing, China. Global cognitive function and executive function were assessed by using the Montreal Cognitive Assessment (MoCA) and Trail Making Tests A (TMT-A), respectively. Oral frailty was identified by the combination of natural tooth, Oral Frailty Index-8 (OFI-8), and oral diadochokinesis. Physical frailty was measured by using Fried phenotype model which contained 5 criteria: unintentional weight loss, weakness, exhaustion, slowness, and low physical activity. Multiple linear regression analyses for overall participants and stratified by sex and presence or absence of physical frailty were performed, respectively, to examine the association between oral frailty and cognitive functions. RESULTS: The median age of participants was 70 years old. The study included 158 (51.5%) females, 53 (17.3%) individuals with physical frailty, and 65 (21.2%) participants with oral frailty. After adjustment, the association between oral frailty and global cognitive function was observed in the physical frailty group (B = -2.67, 95% Confidence Interval [CI]: -5.27 to -0.07, p = 0.045) and the females with physical frailty (B = -4, 95% CI: -7.41 to -0.58, p = 0.024). Oral frailty was associated with executive function in overall participants (B = 0.12, 95% CI: 0.01 to 0.22, p = 0.037), physical frailty group (B = 23.68, 95% CI: 1.37 to 45.99, p = 0.038). In the adjusted models, oral frailty was significantly associated with executive function in all females (B = 0.21, 95% CI: 0.05 to 0.36, p = 0.009), in females without physical frailty (B = 0.19, 95% CI: 0.02 to 0.36, p = 0.027), and in females with physical frailty (B = 48.69, 95% CI: 7.17 to 90.21, p = 0.024). CONCLUSIONS: Physical frailty intensifies the positive association of oral frailty with poor global cognitive function and executive function among older adults, particularly among females. It is ponderable to consider sex differences and facilitate the management of physical frailty when it comes to promoting cognitive health based on the perspective of oral health among older adults.

Tissue-engineered Bicipital Autologous Tendon Patch Enhances Massive Rotator Cuff Defect Repair in a Rabbit Infraspinatus Tendon Defect Model.

BACKGROUND: Massive rotator cuff defects represent an important source of shoulder pain and functional debilitation, substantially diminishing patients' quality of life. The primary treatment of massive rotator cuff defects includes complete or partial repair and patch augmentation. However, because of the tendon's limited regenerative ability, the tendon retear risk after rotator cuff defect repair is still high. Thus, a new therapy is needed to promote tendon regeneration for repair of massive rotator cuff defects. QUESTIONS/PURPOSES: Using an in vitro analysis, we first asked: (1) What is the biocompatibility and collagen synthesis ability of fibrin glue, and what is the cell growth of tissue-engineered bicipital tendon patches, which is comprised of fibrin glue and biceps tendon tissue particles? Then, using an in vivo animal model of full-thickness defects in the infraspinatus tendon in New Zealand White rabbits, we asked: (2) What is the potential of the tissue-engineered bicipital autologous tendon patch to promote tendon regeneration? METHODS: In vitro experiments were conducted to assess the survival, proliferation, and collagen synthesis ability of tendon stem/progenitor cells cultured in fibrin glue. This was achieved through an assay of live/dead cell viability, cell counting kit-8 (CCK-8) assay, and Sirius red staining, respectively. The in vivo animal study was conducted using 8- to 12-week-old New Zealand White rabbits. The left shoulder of each animal was operated on, with equal numbers of males and females. There were 12 rabbits in the control group and 15 rabbits each in the gel and patch groups. Six rabbits were allocated to each of the three groups at the 1- and 3-month time points and three rabbits each were in the gel and patch groups at 2-month time point. Through an infraspinatus tendon defect model, the effectiveness of tissue-engineered bicipital autologous tendon patches (patch group) in tendon repair was assessed compared with untreated (control group) and fibrin glue (gel group) treatments in vivo. This assessment included histological evaluation of repaired tissue morphology, transmission electron microscopy (TEM) evaluation of regenerated collagen fibrils, and RNA sequencing to explore the potential mechanisms of tissue-engineered bicipital autologous tendon patches in tendon regeneration. RESULTS: In vitro experiments demonstrated that fibrin glue enhanced the collagen synthesis ability of tendon stem/progenitor cells (0.38 ± 0.02) compared with standard cell culture alone (0.27 ± 0.02, mean difference 0.11 [95% CI 0.07 to 0.14]; p < 0.001). With prolonged cultivation, the cell growth area of tissue-engineered bicipital tendon patches showed a notable increase after culturing for 14 days (78.13% ± 3.68%) compared with 11 days (13.05% ± 8.78%, mean difference -65.08% [95% CI -77.99% to -52.15%]; p＜0.001), 7 days (2.67% ± 2.62%, mean difference -75.46% [95% CI -88.37% to -62.53%]; p＜0.001), and 1 day (0.33% ± 0.30%, mean difference -77.80% [95% CI -90.71% to -64.87%]; p＜0.001). At 3 months after transplantation, in vivo experiments revealed that compared with the control and gel groups, the patch group displayed improved repair outcomes. This was evidenced by better histological scores in the patch group (3.83 ± 2.01) compared with the gel group (10.67 ± 0.58, mean difference 6.84 [95% CI 3.67 to 10.00]; p = 0.001) and control group (10.75 ± 0.66, mean difference 6.92 [95% CI 3.75 to 10.08]; p = 0.001), and by regular alignment and larger diameters of newly formed collagen fibrils in the patch group (77.52 ± 44.41 nm) compared with the control group (53.34 ± 6.64 nm, mean difference 24.18 [95% CI 22.24 to 26.11]; p < 0.001). RNA sequencing analysis revealed that a tissue-engineered bicipital autologous tendon patch facilitated tendon regeneration by modulating the immune response, promoting collagen fibril organization, and alleviating vasoconstriction. CONCLUSION: This animal study demonstrates that the tissue-engineered bicipital autologous tendon patch effectively modulates an immune response and collagen fibril organization, leading to the promotion of tendon regeneration. CLINICAL RELEVANCE: The tissue-engineered bicipital autologous tendon patch represents a promising strategy for tendon regeneration, offering potential in the repair of massive rotator cuff defects during clinical rotator cuff surgery. Subsequent research could focus on large animal experiments using a tissue-engineered bicipital autologous tendon patch to explore their feasibility for clinical translation.

Preferences for nutrients and sensory food qualities identify biological sources of economic values in monkeys.

Value is a foundational concept in reinforcement learning and economic choice theory. In these frameworks, individuals choose by assigning values to objects and learn by updating values with experience. These theories have been instrumental for revealing influences of probability, risk, and delay on choices. However, they do not explain how values are shaped by intrinsic properties of the choice objects themselves. Here, we investigated how economic value derives from the biologically critical components of foods: their nutrients and sensory qualities. When monkeys chose nutrient-defined liquids, they consistently preferred fat and sugar to low-nutrient alternatives. Rather than maximizing energy indiscriminately, they seemed to assign subjective values to specific nutrients, flexibly trading them against offered reward amounts. Nutrient-value functions accurately modeled these preferences, predicted choices across contexts, and accounted for individual differences. The monkeys' preferences shifted their daily nutrient balance away from dietary reference points, contrary to ecological foraging models but resembling human suboptimal eating in free-choice situations. To identify the sensory basis of nutrient values, we developed engineering tools that measured food textures on biological surfaces, mimicking oral conditions. Subjective valuations of two key texture parameters-viscosity and sliding friction-explained the monkeys' fat preferences, suggesting a texture-sensing mechanism for nutrient values. Extended reinforcement learning and choice models identified candidate neuronal mechanisms for nutrient-sensitive decision-making. These findings indicate that nutrients and food textures constitute critical reward components that shape economic values. Our nutrient-choice paradigm represents a promising tool for studying food-reward mechanisms in primates to better understand human-like eating behavior and obesity.

Recent advances in proton exchange membrane water electrolysis.

Proton exchange membrane water electrolyzers (PEMWEs) are an attractive technology for renewable energy conversion and storage. By using green electricity generated from renewable sources like wind or solar, high-purity hydrogen gas can be produced in PEMWE systems, which can be used in fuel cells and other industrial sectors. To date, significant advances have been achieved in improving the efficiency of PEMWEs through the design of stack components; however, challenges remain for their large-scale and long-term application due to high cost and durability issues in acidic conditions. In this review, we examine the latest developments in engineering PEMWE systems and assess the gap that still needs to be filled for their practical applications. We provide a comprehensive summary of the reaction mechanisms, the correlation among structure-composition-performance, manufacturing methods, system design strategies, and operation protocols of advanced PEMWEs. We also highlight the discrepancies between the critical parameters required for practical PEMWEs and those reported in the literature. Finally, we propose the potential solution to bridge the gap and enable the appreciable applications of PEMWEs. This review may provide valuable insights for research communities and industry practitioners working in these fields and facilitate the development of more cost-effective and durable PEMWE systems for a sustainable energy future.

Co-augmentation of a transport gene mfsT1 in Mycolicibacterium neoaurum with genome engineering to enhance ergothioneine production.

Ergothioneine (EGT) is a rare thiohistidine derivative with exceptional antioxidant properties. The blood level of EGT is considered highly reliable predictors for cardiovascular diseases and mortality, yet animals lack the ability to synthesize this compound. Free plasmids have been previously used to overexpress genes involved in the EGT biosynthetic pathway of Mycolicibacterium neoaurum. Here, we tentatively introduced a putative transporter gene mfsT1 into high-copy plasmids and sharply increased the ratio of extracellular EGT concentration from 18.7% to 44.9%. Subsequently, an additional copy of egtABCDE, hisG, and mfsT1 was inserted into the genome with a site-specific genomic integration tool of M. neoaurum, leading a 2.7 times increase in EGT production. Co-enhancing the S-adenosyl-L-methionine regeneration pathway, or alternatively, the integration of three copies of egtABCDE, hisG and mfsT1 into the genome further increased the total EGT yield by 16.1% (64.6 mg/L) and 21.7% (67.7 mg/L), respectively. After 168-h cultivation, the highest titer reached 85.9 mg/L in the latter strain with three inserted copies. This study provided a solid foundation for genome engineering to increase the production of EGT in M. neoaurum.

Synergistic bioremediation of petroleum-contaminated soil using immobilized consortium of Rhodococcus rhodochrous and Bacillus subtilis laccase.

Petroleum-contaminated soil represents a significant environmental and public health challenge on a global scale. Microbial bioremediation has shown potential, yet the role of enzymes in enhancing petroleum degradation remains underexplored. In this study, the synergistic effects of Rhodococcus rhodochrous (R.rh) and Bacillus subtilis-derived laccase (BsLac) was investigated in the remediation of petroleum-contaminated soil. Immobilized R.rh (PSIMRH) and BsLac (ADIMLac) exhibited higher petroleum degradation rates than their free state, achieving 78.3% and 56.3% degradation in liquid systems, respectively. The combined treatment of PSIMRH and ADIMLac demonstrated a synergistic effect on petroleum degradation, achieving 43.6% with a maximum degradation constant of 0.0335 d-1, representing a 202.7% improvement over untreated soil. PSIMRH enhanced petroleum degradation through microbial metabolism, while ADIMLac accelerated the initial breakdown of complex hydrocarbons into simpler, more bioavailable ones via enzymatic oxidation, providing growth substrates for microbes and significantly improving petroleum degradation rates. The microbial analysis revealed an increase abundance of known petroleum-degrading bacterial genera, including Rhodococcus, Lysobacter, Micromonospora, and Streptomyces. However, the presence of BsLac appeared to reduce the competitive advantage of Rhodococcus, promoting the proliferation of indigenous strains like Lysobacter and Streptomyces. These results suggest that enzyme-microbe synergy can enhance the bioremediation process by altering microbial community dynamics and accelerating petroleum degradation. This study attempts to remediate petroleum-contaminated pollution with the combined use of strains and enzymes, providing a new approach for the remediation of other pollution problems.

Impact of caring leadership on nurses' work engagement: examining the chain mediating effect of calling and affective organization commitment.

BACKGROUND: Previous studies have established a positive link between nurse managers' caring leadership and nurses' work engagement, but the processes and conditions through which this leadership style influences positive work behaviors remain largely unexplored. To address this gap and contribute to the existing body of knowledge, we developed a chain-mediated effects model to elucidate the impact of caring leadership on nurses' work engagement and the underlying mechanisms. In this model, we identified professional mission and affective organizational commitment as the mediating variables, offering a novel perspective on the relationship between caring leadership and work engagement. METHODS: A robust multi-center and large-sample cross-sectional survey was conducted, involving 2502 first-line nurses from six general tertiary hospitals across the eastern, central, and western regions of China. The data collection instruments included a comprehensive questionnaire covering demographic information, the caring leadership scale, the Chinese calling scale, the affective organizational commitment scale, and the Utrecht work engagement scale. Data were meticulously screened and analyzed, employing descriptive analysis to summarize the demographic information, correlation analysis to test the relationship among the variables, stepwise regression analysis to explore the mediating role of calling and affective organization commitment, and the bootstrap method to test the chain mediating effect. This rigorous methodology not only ensures the reliability and validity of research findings but also instills confidence in the robustness of this research. RESULTS: The results indicated a positive relationship among caring leadership, calling, affective organizational commitment, and nurses' work engagement (p < 0.001). Specifically, caring leadership was significantly associated with nurses' calling (ß = 0.55, p < 0.001), affective organizational commitment (ß = 0.21, p < 0.001), and work engagement (ß = 0.05, p < 0.001). And the analysis further revealed that calling and affective organizational commitment mediate the process between caring leadership and work engagement(Effect: 0.17, 0.03, 0.05), with a relative effect size of 89.3% for the total indirect effect. These findings highlight the crucial role of these factors in enhancing nurses' work engagement, providing valuable insights for healthcare leaders and policymakers. CONCLUSION: Caring leadership positively predicts nurses' work engagement and indirectly mediates calling and affective organizational commitment. The results of this study revealed that the mechanisms of caring leadership influence nurses' work engagement, which provides a new approach to strengthening nurses' work engagement and improving patient healthcare outcomes and organizational performance. Healthcare organizations face continuous challenges; this study embodies the significance of caring leadership in improving nurses' work experience and increasing their work engagement. Nursing managers should enhance their knowledge of caring leadership and receive caring leadership training, thus actively improving their leadership behaviors in nurse management, enhancing leadership effectiveness, and creating more possibilities for developing healthcare organizations.

Epidemiology and risk factors of oral frailty among older people: an observational study from China.

OBJECTIVES: This study aimed to compare the prevalence of oral frailty among community-dwelling older people in Nanjing, China with the usage of different measurements, and to investigate the potential risk factors of oral frailty. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: A total of 338 community-dwelling older people in Nanjing, China were recruited. METHODS: Oral frailty was measured based on the Oral Frailty Index-8 (OFI-8) scale and other measurement methods including the number of natural teeth (TN), repetitive saliva-swallowing test (RSST), and oral diadochokinesis (ODK). The chi-square test and the binary logistic regression analysis were performed to identify potential risk factors for oral frailty. RESULTS: There were 310 participants included in the analysis. Prevalence of oral frailty by using the OFI-8, OFI-8 + TN, OFI-8 + ODK, OFI-8 + TN + ODK and RSST measurement methods were 69.0%, 27.4%, 51.9%, 21.0% and 2.9%, respectively. Passive smoking (OR = 2.04; 95%CI 1.03-4.03), being widowed/unmarried (OR1 = 2.53; 95%CI 1.25-5.10; OR2 = 2.94; 95%CI 1.12-7.77), pre-frailty (OR = 1.76; 95%CI 1.03-3.01), frailty (OR = 3.01; 95%CI 1.39-6.54), and aged 80 years and above (OR = 3.99; 95%CI 1.35-11.81) were found to be risk factors of oral frailty by the usage of the four kinds of measurement methods. CONCLUSIONS AND IMPLICATIONS: The definition and diagnostic criteria of oral frailty are strongly needed to be unified in future research. Only subjective assessment is not enough for assessing oral frailty. Among objective indicators, RSST is not suitable as a screening method for oral frailty. In addition, objective indicators including TN and ODK should be valued for early screening and preventive interventions. The risk factors of oral frailty include physical frailty, passive smoking, and being widowed.

[Applications of Artificial Intelligence in Pancreatic Cystic Lesion Imaging].

As the detection rate of pancreatic cystic lesions(PCL)increases,artificial intelligence(AI)has made breakthroughs in the imaging workflow of PCL,including image post-processing,lesion detection,segmentation,diagnosis and differential diagnosis.AI-based image post-processing can optimize the quality of medical images and AI-assisted models for lesion detection,segmentation,diagnosis and differential diagnosis significantly enhance the work efficiency of radiologists.This article reviews the application progress of AI in PCL imaging and provides prospects for future research directions.

Immobilization of the Polar Group into an Ultramicroporous Metal-Organic Framework Enabling Benchmark Inverse Selective CO2/C2H2 Separation with Record C2H2 Production.

One-step harvest of high-purity light hydrocarbons without the desorption process represents an advanced and highly efficient strategy for the purification of target substances. The separation and purification of acetylene (C2H2) from carbon dioxide (CO2) by CO2-selective adsorbents are urgently demanded yet are very challenging owing to their similar physicochemical properties. Here, we employ the pore chemistry strategy to adjust the pore environment by immobilizing polar groups into an ultramicroporous metal-organic framework (MOF), achieving one-step manufacture of high-purity C2H2 from CO2/C2H2 mixtures. Embedding methyl groups into prototype stable MOF (Zn-ox-trz) not only changes the pore environment but also improves the discrimination of guest molecules. The methyl-functionalized Zn-ox-mtz thus exhibits the benchmark reverse CO2/C2H2 uptake ratio of 12.6 (123.32/9.79 cm3 cm-3) and an exceptionally high equimolar CO2/C2H2 selectivity of 1064.9 at ambient conditions. Molecular simulations reveal that the synergetic effect of pore confinement and surfaces decorated with methyl groups provides high recognition of CO2 molecules through multiple van der Waals interactions. The column breakthrough experiments suggest that Zn-ox-mtz dramatically achieved the one-step purification capacity of C2H2 from the CO2/C2H2 mixture with a record C2H2 productivity of 2091 mmol kg-1, surpassing all of the CO2-selective adsorbents reported so far. In addition, Zn-ox-mtz exhibits excellent chemical stability under different pH values of aqueous solutions (pH = 1-12). Moreover, the highly stable framework and excellent inverse selective CO2/C2H2 separation performance showcase its promising application as a C2H2 splitter for industrial manufacture. This work paves the way to developing reverse-selective adsorbents for the challenging gas separation process.

Adjuvant Chemotherapy for Patients with Adenocarcinoma of the Esophagogastric Junction: A Retrospective, Multicenter, Observational Study.

BACKGROUND: Although the incidence of adenocarcinoma of the esophagogastric junction (AEG) has been increasing since the past decade, the proportion of AEG cases in two previous clinical trials (ACTS-GC and CLASSIC) that investigated the efficacy of adjuvant chemotherapy was relatively small. Therefore, whether AEG patients can benefit from adjuvant chemotherapy remains unclear. METHODS: Patients who were diagnosed with pathological stage II/III, Siewert II/III AEG, and underwent curative surgery at three high-volume institutions were assessed. Clinical outcomes were analyzed by using Kaplan-Meier curves, log-rank test, and Cox regression model. Propensity score matching (PSM) was used to reduce the selection bias. RESULTS: A total of 927 patients were included (the chemotherapy group: 696 patients; the surgery-only group: 231 patients). The median follow-up was 39.0 months. The 5-year overall survival was 63.1% (95% confidence interval [CI]: 59.0-67.6%) for the chemotherapy group and 50.2% in the surgery-only group (hazard ratio [HR] = 0.69, 95% CI: 0.54-0.88; p = 0.003). The 5-year, disease-free survival was 35.4% for the chemotherapy group and 16.6% for the surgery-only group (HR = 0.66, 95% CI: 0.53-0.83; p < 0.001). After PSM, the survival benefit of adjuvant chemotherapy for AEG was maintained. Multivariate analysis for overall survival and disease-free survival further demonstrated the survival benefit of adjuvant chemotherapy, with HRs of 0.63 (p < 0.001) and 0.52 (p < 0.001), respectively. CONCLUSIONS: Postoperative adjuvant chemotherapy was associated with improved overall survival and disease-free survival in patients with operable stage II or III AEG after D2 gastrectomy.

Experimental and numerical study of multi-pulse picosecond laser ablation on 316†L stainless steel.

An experimental and numerical study on 10 ps laser ablation of 316 L stainless steel up to 400 hundred pulse exposure has been carried out. In this simulation, the material removal threshold temperature has been carefully discussed depending on the different ablation driving mechanisms. The influence of the instantaneous material removal has also been considered which will affect the calculation of the next pulse's absorption. For single-pulse ablation, the simulated ablation threshold Fsim = 0.26 J/cm2 is close to the fitted experimental result F0th = (0.29 ± 0.01) J/cm2. For multi-pulse ablation, the simulated ablation rate Rsim = 11.4 nm/pulse is close to the fitted experimental result Rexp = (12.4 ± 0.1) nm/pulse under 0.9 J/cm2 fluence, while the simulated ablation rate Rsim = 19.8 nm/pulse is slightly larger than the fitted experimental result Rexp = (16.1 ± 0.7) nm/pulse at 2.7 J/cm2, providing good agreement between theory and experiment for both single and multi-pulse ablation. This study could be used to predict the multi-pulse laser processing performance, especially with the help of a machine learning method to find the best parameters automatically.