Comparative transcriptomic analysis of articular cartilage of post-traumatic osteoarthritis mouse models.

Animal models of post-traumatic osteoarthritis (PTOA) recapitulate the pathological changes observed in human PTOA. Here, skeletally mature C57Bl6 mice were subjected to either the rapid-onset, non-surgical, mechanical anterior cruciate ligament (ACL) rupture or surgical destabilisation of the medial meniscus (DMM) models. Transcriptome profiling of micro-dissected cartilage at day 7 and 42 post-ACL and DMM procedure respectively, showed that the two models were comparable and highly correlative (Spearman R =0.82, p<2.2E-16). Gene ontology enrichment analysis identified similarly enriched pathways, which were overrepresented by anabolic terms. To address the transcriptome changes more completely in the ACL model we also performed small RNA-seq, describing the first microRNA profile of this model. miR-199-5p was amongst the most abundant yet differentially expressed microRNAs and its inhibition in primary human chondrocytes led to a comparable transcriptome response to that observed in both human 'OA damaged vs intact cartilage' and murine DMM cartilage datasets. CELSR1, GIT1, ECE1 and SOS2 were all experimentally verified as novel miR-199-5p targets. Together, these data support the use of the ACL rupture model as a non-invasive companion to DMM.

Study on psychological resilience and associated influencing factors in lung cancer patients with bone metastases.

BACKGROUND: Evaluating the psychological resilience of lung cancer (LC) patients helps understand their mental state and guides future treatment. However, there is limited research on the psychological resilience of LC patients with bone metastases. AIM: To explore the psychological resilience of LC patients with bone metastases and identify factors that may influence psychological resilience. METHODS: LC patients with bone metastases who met the inclusion criteria were screened from those admitted to the Third Affiliated Hospital of Wenzhou Medical University. The psychological scores of the enrolled patients were collected. They were then grouped based on the mean psychological score: Those with scores lower than the mean value were placed in the low-score group and those with scores equal to or greater than the mean value was placed in the high-score group. The baseline data (age, gender, education level, marital status, residence, monthly income, and religious beliefs), along with self-efficacy and medical coping mode scores, were compared. RESULTS: This study included 142 LC patients with bone metastases admitted to our hospital from June 2022 to December 2023, with an average psychological resilience score of 63.24 ± 9.96 points. After grouping, the low-score group consisted of 69 patients, including 42 males and 27 females, with an average age of 67.38 ± 9.55 years. The high-score group consisted of 73 patients, including 49 males and 24 females, with a mean age of 61.97 ± 5.00 years. χ 2 analysis revealed significant differences between the two groups in education level (χ 2 = 6.604, P = 0.037), residence (χ 2 = 12.950, P = 0.002), monthly income (χ 2 = 9.375, P = 0.009), and medical coping modes (χ 2 = 19.150, P = 0.000). Independent sample t-test showed that the high-score group had significantly higher self-efficacy scores (t = 3.383, P = 0.001) and lower age than the low-score group (t = 4.256, P < 0.001). Furthermore, multivariate logistic regression hazard analysis confirmed that self-efficacy is an independent protective factor for psychological resilience [odds ratio (OR) = 0.926, P = 0.035, 95% confidence interval (CI): 0.862-0.995], while age (OR = 1.099, P = 0.003, 95%CI: 1.034-1.169) and medical coping modes (avoidance vs confrontation: OR = 3.767, P = 0.012, 95%CI: 1.342-10.570; resignation vs confrontation: OR = 5.687, P = 0.001, 95%CI: 1.974-16.385) were identified as independent risk factors. A predictive model based on self-efficacy, age, and medical coping modes was developed. The receiver operating characteristic analysis showed an area under the curve value of 0.778 (95%CI: 0.701-0.856, P < 0.001), indicating that the model has good predictive performance. CONCLUSION: LC patients with bone metastases are less psychologically resilient than the general population. Factors such as self-efficacy, age, and medical coping modes influence their psychological resilience. Patients with low self-efficacy, old age, and avoidance/resignation coping modes should be closely observed.

Small molecules targeting selective PCK1 and PGC-1α lysine acetylation cause anti-diabetic action through increased lactate oxidation.

Small molecules selectively inducing peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1α acetylation and inhibiting glucagon-dependent gluconeogenesis causing anti-diabetic effects have been identified. However, how these small molecules selectively suppress the conversion of gluconeogenic metabolites into glucose without interfering with lipogenesis is unknown. Here, we show that a small molecule SR18292 inhibits hepatic glucose production by increasing lactate and glucose oxidation. SR18292 increases phosphoenolpyruvate carboxykinase 1 (PCK1) acetylation, which reverses its gluconeogenic reaction and favors oxaloacetate (OAA) synthesis from phosphoenolpyruvate. PCK1 reverse catalytic reaction induced by SR18292 supplies OAA to tricarboxylic acid (TCA) cycle and is required for increasing glucose and lactate oxidation and suppressing gluconeogenesis. Acetylation mimetic mutant PCK1 K91Q favors anaplerotic reaction and mimics the metabolic effects of SR18292 in hepatocytes. Liver-specific expression of PCK1 K91Q mutant ameliorates hyperglycemia in obese mice. Thus, SR18292 blocks gluconeogenesis by enhancing gluconeogenic substrate oxidation through PCK1 lysine acetylation, supporting the anti-diabetic effects of these small molecules.

Realizing Excellent Infrared Nonlinear Optical Performance in Eu-Based Chalcogenides via Rational Cross Substitution Strategy.

In recent years, rare-earth-based chalcogenides have gained attention promising materials in the field of infrared nonlinear optical (IR-NLO) applications owing to their exceptional physicochemical properties. However, they frequently encounter challenges such as adverse two-photon absorption and low laser-induced damage thresholds (LIDTs) caused by narrow optical band gaps (Eg), which limit their practical utility. In this study, we started with the centrosymmetric (CS) parent compound EuGa2S4 to develop two new noncentrosymmetric (NCS) Eu-based chalcogenides, namely, EuZnSiS4 and EuCdSiS4, employing a rational cross-substitution strategy. Despite having identical stoichiometry, both compounds crystallize in distinct NCS orthorhombic space groups [Fdd2 (no. 43) vs Ama2 (no. 40)], as confirmed by single-crystal structure analysis. Their crystal structures feature highly distorted tetrahedral motifs interconnected via corner-sharing, forming unique two-dimensional layers that host Eu2+ cations. Furthermore, both compounds exhibit robust phase-matching second-harmonic generation (SHG) intensities of 1.5 × AgGaS2 for EuZnSiS4 and 2.8 × AgGaS2 for EuCdSiS4 under 2050 nm excitation. They also demonstrate high LIDTs (approximately 14-17 × AgGaS2), wide Eg (>2.5 eV), and transparency windows extending up to 18.2 µm. Particularly noteworthy, EuCdSiS4 stands out as a pioneering example in the Eu-based IR-NLO system for successfully combining a broad Eg (>2.56 eV, equivalent to that of AgGaS2) with a significant SHG effect (>1.0 × AgGaS2) simultaneously. Structural analyses and theoretical insights underscore that the reasonable combination of asymmetric functional units plays a pivotal role in driving the CS-to-NCS structural transformation and enhancing the NLO and linear optical properties of these Eu-based chalcogenides. This study presents a promising chemical pathway for advancing rare-earth-based functional materials and suggests exciting opportunities for their future applications in IR-NLO technologies.

Adolescent Takayasu's arteritis with hypertensive intracerebral hemorrhage: a case report and literature review.

Takayasu's arteritis is a primary systemic vasculitis that affects predominantly large vessels, affecting the aorta and its major branches. We report a case of adolescent female patient who initially experienced numbness and weakness in her limbs, subsequently developing severe hypertension. Physical examination revealed uneven blood pressure in the limbs and a murmur in the auscultation area of the abdominal aorta without decreased pulses. Auxiliary examinations revealed diffuse blood vessel stenosis, leading to the diagnosis of Takayasu's arteritis. One month later, the patient was diagnosed with multiple cerebral hemorrhages following sudden impairment of limb movement. Digital subtraction angiography did not reveal any evident vascular malformations or aneurysms. Following surgery and biologic intervention with tocilizumab, the patient's condition improved, with no new bleeding episodes and stable blood pressure control achieved. We also reviewed the literature that have been previously reported with hypertensive intracerebral hemorrhage complicated by Takayasu's arteritis. We recommend that Takayasu's arteritis be taken into account when considering the hypertension in young patients. Timely vascular imaging and standardized treatment are imperative for diagnosing and managing effectively.

The Association between Gut Microbiota and Its Metabolites in Gestational Diabetes Mellitus.

Gut microbial metabolites have been demonstrated to play a role in diabetes mellitus and gestational diabetes mellitus (GDM). This study aimed to investigate gut microbiome, fecal metabolomics, and their association in pregnant women with and without GDM. The metabolome indicated that the top 2 differential metabolic pathways between control (Con) and GDM groups were phenylalanine metabolism and nucleotide metabolism. The increased Phenylalanylglycine, m-coumaric acid, and Phenylacetic acid were among the top differential metabolites between Con and GDM groups and involved in phenylalanine metabolism. Uracil and hypoxanthine were top differential metabolites in Con vs. GDM and involved in nucleotide metabolism. The proficiently altered gut microbiota at the class level was c_unclassified_ Firmicutes. Association analysis between gut microbiota and fecal metabolites indicated that the increased gut symbiont Clostridium belonged to Firmicutes and was linked to the dysregulation of phenylalanine metabolism in GDM. This study may provide the mechanism underlying how Clostridium-phenylalanine metabolism association contributes to GDM pathogenesis and also be a novel therapeutic strategy to treat GDM.

[Relationship Between Physical Activity and Depressive Symptoms Among Middle-Aged and Older Adults in Chengdu,Sichuan,China].

Objective To investigate the current status of physical activity and depressive symptoms among middle-aged and older adults in Chengdu,Sichuan and explore the relationship between physical activity and depressive symptoms. Methods Multi-stage proportional stratified random sampling was employed to select middle-aged and older adults aged ≥45 years as the participants,and face-to-face interviews were carried out to collect data.Logistic regression was adopted to explore the relationship between physical activity and depressive symptoms in middle-aged and older adults.The trend test was performed for the relationship between different levels of physical activity and depressive symptoms.The subgroup analysis and the test for multiplicative interactions were conducted for the relationship between physical activity and depressive symptoms. Results A total of 4376 middle-aged and older adults were included.Among them,14.58% (638/4376),25.98% (1137/4376),and 27.83% (1218/4376) had depressive symptoms,failed to reach the guideline-recommended standards of physical activity,and were at low levels of physical activity,respectively.There was a negative association between reaching guideline-recommended physical activity standard and depressive symptoms in middle-aged and older adults (OR=0.713,95%CI=0.589-0.861,P<0.001).In addition,moderate levels (OR=0.714,95%CI=0.586-0.871,P=0.001) and high levels of physical activity (OR=0.705,95%CI=0.548-0.906,P=0.006) had negative associations with the presence of depressive symptoms.The trend test revealed that the negative association between physical activity and depressive symptoms in middle-aged and older adults enhanced as the level of physical activity increased (Pfor trend=0.001).The subgroup analysis and the test for multiplicative interactions revealed that neither reaching guideline-recommended physical activity standards or not nor the physical activity level had an interaction with each of the subgroups (all Pfor interaction>0.05). Conclusion The current status of depressive symptoms among middle-aged and older adults in Chengdu,Sichuan needs to be ameliorated.A negative association existed between reaching the guideline-recommended physical activity standard and presence of depressive symptoms,and the negative association enhanced as the physical activity level elevated.

Developmental trajectories of professional preparedness among senior nursing students during clinical placement: A longitudinal study.

BACKGROUND: Newly graduated nurses' lack of professional competence is associated with inadequate preparation during their clinical placement as nursing students. Clinical placement is a critical stage in the development of nursing students' professional preparedness. However, research on the trajectory of nursing students' professional preparedness during clinical placement has not yielded findings with the same specificity. OBJECTIVES: The aim of this study is to estimate differences in professional preparedness levels at different clinical placement stages, to identify distinct patterns of professional preparedness trajectories during clinical placement, and to evaluate predictors of these trajectory group memberships. DESIGN: A quantitative longitudinal study. SETTINGS: Participants were recruited on a voluntary basis using convenience sampling at a tertiary hospital in Nanning, China. PARTICIPANTS: 224 senior nursing students were initially invited to participate in the study. A total of 178 nursing students successfully completed the follow-up assessments at baseline, as well as at 1 month, 4 months, and 8 months into their clinical placement. METHODS: Participants completed four online surveys, during which their professional preparedness level was measured using the Perceived Professional Preparedness questionnaire for senior nursing students. Professional preparedness scores at different time points were compared using one-way repeated measures ANOVA and latent growth model. Group-based trajectory model was applied to identify professional preparedness trajectories. Multiple logistic regression was adopted to determine the predictors of trajectory group memberships. RESULTS: The entire sample of Senior nursing students experienced a significant increase in professional preparedness during clinical placement. The best-fitting group-based trajectory model delineated three distinct trajectories: low-slowly increase trajectory (27.53 % of sample), moderate-rapidly increase trajectory (47.19 % of sample) and a high-stably increase trajectory (25.28 % of sample). Male, good and excellent academic performance, and very high degree of professional interest are the predictors of the moderate-rapidly increase trajectory. While male, good and excellent academic performance, high and very high degree of professional interest and participating in medical-related part-time employment are the predictors of the high-stable increase trajectory. CONCLUSIONS: Senior nursing students exhibit different levels of professional preparedness throughout their clinical placement. Simultaneously, three different trajectories were identified among the sample of nursing students. Therefore, in future research, greater attention should be directed towards the professional preparedness levels of nursing students with different trajectories, and early identification and targeted interventions should be prioritized.

Post-translational modifications in sepsis-induced organ dysfunction: mechanisms and implications.

As a grave and highly lethal clinical challenge, sepsis, along with its consequent multiorgan dysfunction, affects millions of people worldwide. Sepsis is a complex syndrome caused by a dysregulated host response to infection, leading to fatal organ dysfunction. An increasing body of evidence suggests that the pathogenesis of sepsis is both intricate and rapid and involves various cellular responses and signal transductions mediated by post-translational modifications (PTMs). Hence, a comprehensive understanding of the mechanisms and functions of PTMs within regulatory networks is imperative for understanding the pathological processes, diagnosis, progression, and treatment of sepsis. In this review, we provide an exhaustive and comprehensive summary of the relationship between PTMs and sepsis-induced organ dysfunction. Furthermore, we explored the potential applications of PTMs in the treatment of sepsis, offering a forward-looking perspective on the understanding of infectious diseases.

Antifungal effect of cinnamon essential oil against Penicillium oxalicum on rice noodles.

Plant essential oils have been extensively investigated for their application in food industry due to their broad antimicrobial spectrum and safety. However, rare studies investigated their application in decontaminating rice noodles from fungal contamination. In this study, the cinnamon essential oil was screened out among 12 species of plant essential oils, and its antifungal activity against Penicillium oxalicum isolated from rice noodles was investigated. Our study revealed that cinnamon essential oil inhibited the spore germination in a concentration-dependent manner, and a dosage of 0.025% (v/v) could entirely disable the spore germination. The disruption of the fungal plasma membrane was evidenced by the change of plasma membrane permeability and the leakage of cellular components. The cinnamon essential oil in vapor phase (0.00625% [v/v]) could totally inhibit the growth of fungi inoculated on rice noodles. In addition to the potential application in inactivating fungi germination on rice noodles, this study also demonstrated the feasibility of cinnamon essential as an environmental disinfectant. This study is the first report that cinnamon essential oil has been studied for decontaminating rice noodles from fungal contamination with P. oxalicum, which not only broadens the application field of plant essential oil but also provides an alternative approach for rice noodle preservation.

SERPINA3 is a marker of cartilage differentiation and is essential for the expression of extracellular matrix genes during early chondrogenesis.

Serine proteinase inhibitors (serpins) are a family of structurally similar proteins which regulate many diverse biological processes from blood coagulation to extracellular matrix (ECM) remodelling. Chondrogenesis involves the condensation and differentiation of mesenchymal stem cells (MSCs) into chondrocytes which occurs during early development. Here, and for the first time, we demonstrate that one serpin, SERPINA3 (gene name SERPINA3, protein also known as alpha-1 antichymotrypsin), plays a critical role in chondrogenic differentiation. We observed that SERPINA3 expression was markedly induced at early time points during in vitro chondrogenesis. We examined the expression of SERPINA3 in human cartilage development, identifying significant enrichment of SERPINA3 in developing cartilage compared to total limb, which correlated with well-described markers of cartilage differentiation. When SERPINA3 was silenced using siRNA, cartilage pellets were smaller and contained lower proteoglycan as determined by dimethyl methylene blue assay (DMMB) and safranin-O staining. Consistent with this, RNA sequencing revealed significant downregulation of genes associated with cartilage ECM formation perturbing chondrogenesis. Conversely, SERPINA3 silencing had a negligible effect on the gene expression profile during osteogenesis suggesting the role of SERPINA3 is specific to chondrocyte differentiation. The global effect on cartilage formation led us to investigate the effect of SERPINA3 silencing on the master transcriptional regulator of chondrogenesis, SOX9. Indeed, we observed that SOX9 protein levels were markedly reduced at early time points suggesting a role for SERPINA3 in regulating SOX9 expression and activity. In summary, our data support a non-redundant role for SERPINA3 in enabling chondrogenesis via regulation of SOX9 levels.

Constructed wetlands and hyperaccumulators for the removal of heavy metal and metalloids: A review.

Water pollutions of heavy metal and metalloids (HMMs), typically including As, Cd, Cu, Cr, Mn, Ni, Pb, and Zn, are becoming a severe environmental problem to be controlled. Constructed wetlands (CWs) have been intensively investigated and applied for the removal of HMMs. By analyzing a mass of data from the existing literatures, this review found that the HMM removals in CWs varied from 12.35 % to 91.01 %, depending upon the HMM species and CW conditions. Nonetheless, 88.50 % of the influent HMMs were eventually immobilized in the CW sediments, while the common wetland plants are inefficient (i.e., accounting for 4.64 %) to uptake and accumulate the HMMs. It was also found that the concentrations of certain HMMs in the CW sediments have already exceeded up to 100 % of various environmental standards, indicating the urgency of introducing HMM hyperaccumulators in the systems. Through comparison, both the aboveground and belowground HMM accumulating capacities of reported hyperaccumulators were higher by magnitudes than common wetland plants. Following this, the efficacies and mechanisms of candidate hyperaccumulators were provided for the various scenarios of HMM control in CWs. Further, the selection principals, culture methods, and harvest strategies of hyperaccumulator in CWs were discussed. Finally, several perspectives were suggested for the future research. Overall, this review provided guiding information for the utilization of hyperaccumulators in CWs, which can improve the efficiency and sustainability of HMM removal in the CW systems.

Characteristics of imaging in hepatic inflammatory pseudotumors: a comparison between IgG4-related and IgG4-unrelated cases.

OBJECTIVES: The objective of this study was to examine the imaging features of hepatic inflammatory pseudotumors (IPTs) associated with IgG4-related and IgG4-unrelated conditions and to enhance the approach toward distinguishing between these two types of IPTs. METHODS: A retrospective study was conducted, involving 20 patients diagnosed with hepatic IPTs. Imaging procedures were conducted within a timeframe of 4 weeks prior to hepatectomy or biopsy. The imaging features were then analyzed and compared using chi-squared analysis. RESULTS: Seventeen (81.0%) IPTs were located in the hepatic subcapsular area; six (66.7%) IgG4-related IPTs were distributed around the hepatic hilum; and eleven (91.7%) IgG4-unrelated and three (33.3%) IgG4-related IPTs had unclear boundaries. All lesions exhibited similar characteristics in CT scans, T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and diffusion-weighted imaging (DWI), with the apparent diffusion coefficient (ADC) values slightly higher than the surrounding liver tissue. Delayed hypoenhancement, observed in five cases (55.6%), was exclusively present in IgG4-related IPTs. The remaining IPT lesions displayed progressive enhancement, septal and marginal enhancement, and persistent enhancement. Central enhancement was absent in three IgG4-related IPTs (33.3%) and ten IgG4-unrelated IPTs (83.3%). The duct-penetrating sign was identified in two IgG4-unrelated IPTs (16.7%) and seven IgG4-related IPTs (77.8%). Furthermore, seven patients with IgG4-related IPTs had additional lesions outside the liver. CONCLUSIONS: IgG4-related lesions are frequently found in the vicinity of the hepatic hilum; they display the duct-penetrating sign and affect other organs as well. Both groups exhibited progressive or persistent contrast enhancement in typical IPT lesions, but delayed hypoenhancement was only observed in the IgG4-related IPT group. IgG4-unrelated IPT lesions often exhibited indistinct boundaries lacking central enhancement. CRITICAL RELEVANCE STATEMENT: Differences in imaging features differentiate IgG4-related and -unrelated inflammatory pseudotumors (IPT). IgG4-related lesions are frequently near the hepatic hilum, display duct-penetrating sign, and affect other organs. Only the IgG4-related group demonstrated delayed hypoenhancement. IgG4-unrelated IPT lesions often exhibited indistinct boundaries lacking central enhancement. KEY POINTS: Compared with IgG 4-unrelated IPTs, IgG4-related IPTs show delayed hypoenhancement and affect other organs. IgG4-unrelated IPTs have unclear boundaries and lack central enhancement. Improved IPT diagnostic capabilities can help minimize additional, potentially unnecessary, interventions.

A Psychometric Development and Evaluation of the Flow State Scale for Caregiving Tasks Among Clinical Nurses.

BACKGROUND: The extensive research already conducted in numerous non-healthcare disciplines has consistently demonstrated the effectiveness of flow in alleviating work-related stress and boosting employee engagement in the workplace. Despite the potential benefits to nursing of improving flow, no valid instrument is currently available to measure the work-related flow experience of clinical nurses. PURPOSE: This study was designed to develop the Flow State Scale for Caregiving Tasks (FSS-CT) and to evaluate its psychometric properties in the context of clinical nurses. METHODS: This study, guided by the flow theory of Mihaly Csikszentmihalyi (1975), employed a three-phase approach to developing and evaluating the psychometric properties of the FSS-CT. Five hundred thirty-six full-time clinical nurses working in hospitals of various levels in Taiwan were recruited via cluster random sampling to participate in an anonymous online survey. The content validity of the developed scale was established through expert panel verification, criterion-related validity was assessed by correlating the scale with the Work-related Flow Inventory, and construct validity was evaluated via explanatory and confirmatory factor analyses. Scale reliability was determined using Cronbach's α coefficient. RESULTS: The FSS-CT, a 12-item Likert scale comprising four domains, was developed. These domains capture the elements of nurses' work-related flow, including professional confidence, merging of action and awareness, balance between skill and challenge, and autotelic experience. The FSS-CT demonstrated high content validity (content validity index > .90) and satisfactory criterion-related validity (coefficient = .55, p < .001). Furthermore, the scale was found to have excellent internal consistency (Cronbach's α = .91). Factor analyses yielded a four-factor structure accounting for 69.34% of the total variance, indicating a good fit for the final model based on recommended goodness-of-fit indices. CONCLUSIONS: The FSS-CT is a viable and dependable instrument for assessing the work-related flow experiences of nurses, with the measured outcomes offering to nursing administrators valuable insights into or directions for personnel development and work allocation initiatives.

Bi-functional NiFe2O4/SrTiO3 S-scheme heterojunction for eminent performance photocatalytic treatment of sewage effluent and electrochemical hydrazine determination.

Devising of materials that afforded dual applicability in decontamination and pollutant detection were still a towering challenge owing to the increasing flux of discharge toxic contaminants over the years. Herein, the NiFe2O4 nanoparticles-loaded on cube-like SrTiO3 (NiFe2O4/SrTiO3) composite was fabricated by a two-step hydrothermal approach providing remarkable photocatalytic treatment and electrochemical sensing of noxious pollutants in wastewater. The material traits of the fabricated composite were scrutinized by myriad characterization approaches. The NiFe2O4/SrTiO3 hybrid material demonstrated high surface area of 19.81 m2/g, adequate band gap energy of 2.75 eV, and prominent photoluminescence characteristics. In the presence of visible light, the NiFe2O4/SrTiO3 exhibited profound photocatalysis capability to eliminate sewage effluent-bearing chlortetracycline hydrochloride (CTCH) with 88.6% COD removal in 120 min, outperforming other pure materials. Meanwhile, the toxicity examination of effluent, the possible degradation pathway of CTCH and the proposed photocatalysis mechanism were also divulged. More importantly, the glassy carbon electrode was modified with synergized NiFe2O4/SrTiO3 (NiFe2O4/SrTiO3-GCE) was adopted for the precise quantification of Hydrazine (Hz). The NiFe2O4/SrTiO3-GCE obeyed first-order response for the Hz detection within the range of 1-10 mM: cyclic voltametric: limit of detection (LOD) of 0.119 µM with sensitivity of 18.9 µA µM-1 cm-2, and linear sweep voltametric: LOD of 0.222 µM with a sensitivity of 12.05 µA µM-1 cm-2. The stability and interference of modified electrode were also inspected. This work furnished valuable insights to yield a composite with the prominent S-scheme heterojunction system for quenching of charge carrier recombination and consequently contributing to the future realization into the domains of environmental clean-up and toxic chemical detection.

Screening Strategy Identifies an Overlooked Deep-Ultraviolet Transparent Nonlinear Optical Crystal.

In the deep-ultraviolet (DUV) region, nonlinear optical (NLO) crystals must meet stringent requirements, including a large optical band gap and sufficient second harmonic generation (SHG) response. Typically, these criteria are fulfilled by borates, carbonates and nitrates containing π-conjugated groups. In contrast, sulfates and phosphates, with polarizabilities significantly smaller than those of π-conjugated groups, struggle to achieve similar performance. Here, we present the discovery of Mg2PO4Cl, a magnesium-based phosphate, identified from over 10,000 phosphates based on a polar-axial-symmetry screening strategy, which exhibits the highest SHG response (5.2 × KH2PO4 (KDP)) with phase-matching ability among non-π-conjugated DUV transparent NLO crystals. This compound belongs to the Pna21 space group, with [PO4] units consistently aligned along the 21 screw axis and glide planes throughout its crystal structure. Theoretical calculations attribute its remarkable SHG effect to the orderly arrangement of heteroanionic [MgO5Cl] and [MgO4Cl2] polyhedra alongside isolated [PO4] tetrahedra, supported by Berry phase analysis. Furthermore, a crystallographic structure analysis of phosphates and sulfates with significant SHG effects validates the effectiveness of our screening strategy. These findings offer valuable insights into the origins of NLO effects in non-π-conjugated compounds from both a material design and structural chemistry perspective, inspiring future efforts to revitalize DUV phosphates.

Dual-site molecular glues for enhancing protein-protein interactions of the CDK12-DDB1 complex.

Protein-protein interactions (PPIs) stabilization with molecular glues plays a crucial role in drug discovery, albeit with significant challenges. In this study, we propose a dual-site approach, targeting the PPI region and its dynamic surroundings. We conduct molecular dynamics simulations to identify critical sites on the PPI that stabilize the cyclin-dependent kinase 12 - DNA damage-binding protein 1 (CDK12-DDB1) complex, resulting in further cyclin K degradation. This exploration leads to the creation of LL-K12-18, a dual-site molecular glue, which enhances the glue properties to augment degradation kinetics and efficiency. Notably, LL-K12-18 demonstrates strong inhibition of gene transcription and anti-proliferative effects in tumor cells, showing significant potency improvements in MDA-MB-231 (88-fold) and MDA-MB-468 cells (307-fold) when compared to its precursor compound SR-4835. These findings underscore the potential of dual-site approaches in disrupting CDK12 function and offer a structural insight-based framework for the design of cyclin K molecular glues.

Unlocking the potential: strategic synthesis of a previously predicted pyrazolate-based stable MOF with unique clusters and high catalytic activity.

The metal-organic framework (MOF) constructed from [Co4Pz8] clusters (Pz = pyrazolate) and 1,3,5-tris(pyrazolate-4-yl) benzene (BTP3-) ligands was structurally predicted many years ago, and expected to be a promising candidate for various applications owing to its unique clusters and highly open 3D framework structure. However, this MOF has not been experimentally prepared yet, despite extensive efforts were made. In this work, we present the successful construction of this MOF, hereinafter referred to as BUT-124(Co), by adopting a two-step synthesis strategy, involving the initial construction of a template framework (BUT-124(Cd)) followed by a post-synthetic metal metathesis process. The effects of various cobalt sources and solvents were systematically investigated, and an innovative stepwise metathesis strategy was employed to optimize the exchange rates and the porosity of the material. BUT-124(Co) demonstrates high catalytic activity in the oxygen evolution reaction (OER), achieving a competitive performance with an overpotential of 393 mV at a current density of 10 mA cm-2, and also affords remarkable long-term stability during potentiostatic electrolysis in 1 M KOH solution, surpassing the durability of many benchmark catalysts. This work not only introduces a novel MOF material with promising properties but also exemplifies a strategic synthesis approach for pyrazolate-based MOFs, paving the way for advancements in diverse application fields.

Evaluation of Factors Influencing Postoperative Cognitive Dysfunction in Patients After Cranial Tumor Surgery.

BACKGROUND: The authors retrospectively analyzed the perioperative data of 81 patients who underwent cranial tumor surgery to explore the factors influencing POCD in patients after the surgery. METHODS: The authors evaluated preoperative cognitive dysfunction using the Mini-Mental State Examination (MMSE) score measured. For patients whose cognitive function was normal, the authors retrieved the MMSE score on the seventh day after surgery and compared it to determine whether the patients had POCD. The authors used a univariate logistic regression analysis to analyze the perioperative factors in patients, namely, age, gender, history of underlying diseases, tumor size, peritumoral edema, duration of surgery, blood loss, intraoperative fluid infusion, and type of anesthetic drugs. The authors then performed a multivariate logistic regression analysis for the statistically significant factors. RESULTS: The authors found that 23 of 81 patients (28.4%) developed POCD. Univariate logistic analysis showed that a history of diabetes mellitus, peritumoral edema, intraoperative blood loss, and anesthetic drugs were the risk factors for patients developing POCD after cranial tumor surgery. Multivariate logistic regression analysis showed that a history of diabetes mellitus, peritumoral edema, and use of ciprofol as the anesthetic drug were independent risk factors for POCD after cranial tumor surgery. CONCLUSIONS: A history of diabetes mellitus, the degree of brain tumor edema, and the choice of anesthetic drugs significantly influence the occurrence of POCD in patients after cranial tumor surgery.

Electroacupuncture activates AMPKα1 to improve learning and memory in the APP/PS1 mouse model of early Alzheimer's disease by regulating hippocampal mitochondrial dynamics.

OBJECTIVE: Studies have shown that electroacupuncture (EA) can alleviate cognitive impairments from Alzheimer's disease (AD) by regulating the expression of adenosine monophosphate-activated protein kinase (AMPK), but the specific mechanism involved remains to be elucidated. Therefore, this study explores the potential mechanism by which EA improves cognitive function from the perspective of mitochondrial dynamics. METHODS: The four-month-old transgenic mice with amyloid precursor protein (APP)/presenilin 1 (PS1) and AMPKα1-subunit conditional knockout (AMPKα1-cKO) were used for experiments. To evaluate the effects of EA treatment on cognitive function, the T-maze and Morris water maze were used. In addition, chemical exchange saturation transfer, thioflavin staining, transmission electron microscopy, mitochondrial membrane potential, and Western blotting were used to examine the potential mechanisms underlying the effects of EA on APP/PS1 mice. RESULTS: Both APP/PS1 mice and AMPKα1-cKO mice exhibited dysfunction in mitochondrial dynamics accompanied by learning and memory impairment. Inactivation of the AMPK/peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) pathway increased pathological amyloid-ß (Aß) deposition and aggravated the dysfunction in mitochondrial dynamics. In addition, EA rescued learning and memory deficits in APP/PS1 mice by activating the AMPK/PGC-1α pathway, specifically by reducing pathological Aß deposition, normalizing energy metabolism, protecting the structure and function of mitochondria, increasing the levels of mitochondrial fusion proteins, and downregulating the expression of fission proteins. However, the therapeutic effect of EA on cognition in APP/PS1 mice was hindered by AMPKα1 knockout. CONCLUSION: The regulation of hippocampal mitochondrial dynamics and reduction in Aß deposition via the AMPK/PGC-1α pathway are critical for the ability of EA to ameliorate cognitive impairment in APP/PS1 mice. Please cite this article as: Jia WW, Lin HW, Yang MG, Dai YL, Ding YY, Xu WS, Wang SN, Cao YJ, Liang SX, Wang ZF, Chen C, Liu WL. Electroacupuncture activates AMPKα1 to improve learning and memory in the APP/PS1 mouse model of early Alzheimer's disease by regulating hippocampal mitochondrial dynamics. J Integr Med. 2024; 22(5): 588-599.