The crucial role of NR2A mediating the activation of satellite glial cells in the trigeminal ganglion contributes to orofacial inflammatory pain during TMJ inflammation.

Temporomandibular joint inflammatory diseases are a significant subtype of temporomandibular disorders (TMD) characterized by inflammatory pain in the orofacial area. The N-methyl-D-aspartate receptor (NMDAR), specifically the NR2A subtype, was crucial in neuropathic pain. However, the exact role of NR2A in inflammatory pain in the TMJ and the molecular and cellular mechanisms mediating peripheral sensitization in the trigeminal ganglion (TG) remain unclear. This study utilized male and female mice to induce the TMJOA model by injecting Complete Freund's adjuvant (CFA) into the TMJ and achieve conditional knockout (CKO) of NR2A in the TG using Cre/Loxp technology. The Von-Frey filament test results showed that CFA-induced orofacial pain with reduced mechanical withdrawal threshold (MWT), which was not developed in NR2A CKO mice. Additionally, the up-regulation of interleukin (IL)-1ß, IL-6, and nerve growth factor (NGF) in the TG induced by CFA did not occur by NR2A deficiency. In vitro, NMDA activated satellite glial cells (SGCs) with high expression of glial fibrillary acidic protein (GFAP), and both NMDA and LPS led to increased IL-1ß, IL-6, and NGF in SGCs. NR2A deficiency reduced these stimulating effects of NMDA and LPS. The regulation of IL-1ß involved the p38, Protein Kinase A (PKA), and Protein Kinase C (PKC) pathways, while IL-6 signaling relied on PKA and PKC pathways. NGF regulation was primarily through the p38 pathway. This study highlighted NR2A's crucial role in the TG peripheral sensitization during TMJ inflammation by mediating ILs and NGF, suggesting potential targets for orofacial inflammatory pain management.

Silencing AREG Enhances Sensitivity to Irradiation by Suppressing the PI3K/AKT Signaling Pathway in Colorectal Cancer Cells.

Background: It has been established that Spalt-Like Transcription Factor 4 (SALL4) promotes Colorectal Cancer (CRC) cell proliferation. Furthermore, Amphiregulin (AREG) is crucially involved in cancer cell proliferation and therapeutic resistance regulation. In this regard, this study aimed to establish whether SALL4 affects the radiosensitization of CRC cells via AREG expression regulation. Methods: Transcriptome sequencing and the Human Transcription Factor Database (HumanTFDB) were used to identify the potential SALL4 targets. The dual-luciferase reporter analysis was used to confirm the SALL4-induced AREG activation. Western Blot (WB) and Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR) assays were used to examine the effect of X-ray irradiation on SALL4 and AREG expression. The AREG-KD (Knockdown) stable cell lines were created through lentiviral infection. Cell proliferation was tracked using Cell Counting Kit 8 (CCK-8) and 5-Ethynyl-2'-deoxyuridine (EdU)-incorporation assays. Cell cycle and apoptosis were examined through flow cytometry. The cells were exposed to a controlled X-ray radiation dose (6 Gy) for imaging purposes. Results: SALL4 could bound to the AREG promoter, enhancing AREG expression. Furthermore, irradiation upregulated SALL4 and AREG in CRC cells. Additionally, AREG knockdown in CRC cells led to reduced DNA replication efficiency, suppressed cell proliferation, increased DNA damage, and enhanced G1 phase arrest and apoptosis following irradiation. On the other hand, AREG overexpression reversed the inhibitory effects of SALL4 downregulation on AREG expression. Conclusion: In CRC cells, SALL4 downregulation suppressed AREG expression, regulating CRC cell radiosensitivity via the PI3K-AKT pathway, thus presenting a potential therapeutic pathway for CRC treatment using Radiotherapy (RT).

The role and therapeutic potential of itaconate in lung disease.

Lung diseases triggered by endogenous or exogenous factors have become a major concern, with high morbidity and mortality rates, especially after the coronavirus disease 2019 (COVID-19) pandemic. Inflammation and an over-activated immune system can lead to a cytokine cascade, resulting in lung dysfunction and injury. Itaconate, a metabolite produced by macrophages, has been reported as an effective anti-inflammatory and anti-oxidative stress agent with significant potential in regulating immunometabolism. As a naturally occurring metabolite in immune cells, itaconate has been identified as a potential therapeutic target in lung diseases through its role in regulating inflammation and immunometabolism. This review focuses on the origin, regulation, and function of itaconate in lung diseases, and briefly discusses its therapeutic potential.

Stereoselective Construction of the ABCDE Pentacyclic Motif of Phainanoids via Norrish-Yang Photocyclization Reaction.

A Norrish-Yang photocyclization reaction has been applied to regio- and stereoselective construction of the ABCDE pentacyclic motif of natural product phainanoids. The observed substrate conformation control implicates this powerful reaction could be applied to the construction of structurally diverse natural product scaffolds.

Opportunistic Assessment of Hip Fracture Risk Based on Chest CT.

OBJECTIVE: Hip fracture (HF) has been described as the "last fracture of life" in the elderly, so the assessment of HF risk is extremely important. Currently, few studies have examined the relationship between imaging data from chest computed tomography (CT) and HF. This study demonstrated that pectoral muscle index (PMI) and vertebral body attenuation values could predict HF, aiming to opportunistically assess the risk of HF in patients without bone mineral density (BMD) based on chest CT for other diseases. METHODS: In the retrospective study, 800 participants who had both BMD and chest CT were enrolled from January 2021 to January 2024. After exclusion, 472 patients were finally enrolled, divided into the healthy control (HC) group and the HF group. Clinical data were collected, and differences between the two groups were compared. A predictive model was constructed based on the PMI and CT value of the fourth thoracic vertebra (T4HU) by logistic regression analysis, and the predictive effect of the model was analyzed by using the receiver operating characteristic (ROC) curve. Finally, the clinical utility of the model was analyzed using decision curve analysis (DCA) and clinical impact curves. RESULTS: Both PMI and T4HU were lower in the HF group than in the HC group (p < 0.05); low PMI and low T4HU were risk factors for HF. The predictive model incorporating PMI and T4HU on the basis of age and BMI had excellent diagnostic efficacy with an area under the curve (AUC) of 0.865 (95% confidence interval [CI]: 0.830-0.894, p < 0.01), sensitivity and specificity of 0.820 and 0.754, respectively. The clinical utility of the model was validated using calibration curves and DCA. The AUC of the predictive model incorporating BMD based on age and BMI was 0.865 (95% CI: 0.831-0.895, p < 0.01), with sensitivity and specificity of 0.698 and 0.711, respectively. There was no significant difference in diagnostic efficacy between the two models (p = 0.967). CONCLUSIONS: PMI and T4HU are predictors of HF in patients. In the absence of dual-energy x-ray absorptiometry (DXA), the risk of HF can be assessed by measuring the PMI and T4HU on chest CT examination due to other diseases, and further treatment can be provided in time to reduce the incidence of HF.

Isolation, characterization, and genomic analysis of a lytic bacteriophage, PQ43W, with the potential of controlling bacterial wilt.

Bacterial wilt (BW) is a devastating plant disease caused by the soil-borne bacterium Ralstonia solanacearum species complex (Rssc). Numerous efforts have been exerted to control BW, but effective, economical, and environmentally friendly approaches are still not available. Bacteriophages are a promising resource for the control of bacterial diseases, including BW. So, in this study, a crop BW pathogen of lytic bacteriophage was isolated and named PQ43W. Biological characterization revealed PQ43W had a short latent period of 15 min, 74 PFU/cell of brust sizes, and good stability at a wide range temperatures and pH but a weak resistance against UV radiation. Sequencing revealed phage PQ43W contained a circular double-stranded DNA genome of 47,156 bp with 65 predicted open reading frames (ORFs) and genome annotation showed good environmental security for the PQ43W that no tRNA, antibiotic resistance, or virulence genes contained. Taxonomic classification showed PQ43W belongs to a novel genus of subfamily Kantovirinae under Caudoviricetes. Subsequently, a dose of PQ43W for phage therapy in controlling crop BW was determined: 108 PFU*20 mL per plant with non-invasive irrigation root application twice by pot experiment. Finally, a field experiment of PQ43W showed a significantly better control effect in crop BW than the conventional bactericide Zhongshengmycin. Therefore, bacteriophage PQ43W is an effective bio-control resource for controlling BW diseases, especially for crop cultivation.

The additive effect of the triglyceride-glucose index and estimated glucose disposal rate on long-term mortality among individuals with and without diabetes: a population-based study.

BACKGROUND: The triglyceride-glucose (TyG) index and estimated glucose disposal rate (eGDR), which are calculated using different parameters, are widely used as markers of insulin resistance and are associated with cardiovascular diseases and prognosis. However, whether they have an additive effect on the risk of mortality remains unclear. This study aimed to explore whether the combined assessment of the TyG index and eGDR improved the prediction of long-term mortality in individuals with and without diabetes. METHODS: In this cross-sectional and cohort study, data were derived from the National Health and Nutrition Examination Survey (NHANES) 2001-2018, and death record information was obtained from the National Death Index. The associations of the TyG index and eGDR with all-cause and cardiovascular mortality were determined by multivariate Cox regression analysis and restricted cubic splines. RESULTS: Among the 17,787 individuals included in the analysis, there were 1946 (10.9%) all-cause deaths and 649 (3.6%) cardiovascular deaths during a median follow-up of 8.92 years. In individuals with diabetes, the restricted cubic spline curves for the associations of the TyG index and eGDR with mortality followed a J-shape and an L-shape, respectively. The risk of mortality significantly increased after the TyG index was > 9.04 (all-cause mortality) or > 9.30 (cardiovascular mortality), and after eGDR was < 4 mg/kg/min (both all-cause and cardiovascular mortality). In individuals without diabetes, the association between eGDR and mortality followed a negative linear relationship. However, there was no association between the TyG index and mortality. Compared with individuals in the low TyG and high eGDR group, those in the high TyG and low eGDR group (TyG > 9.04 and eGDR < 4) showed the highest risk for all-cause mortality (hazard ratio [HR] = 1.592, 95% confidence interval [CI] 1.284-1.975) and cardiovascular mortality (HR = 1.683, 95% CI 1.179-2.400) in the overall population. Similar results were observed in individuals with and without diabetes. CONCLUSIONS: There was a potential additive effect of the TyG index and eGDR on the risk of long-term mortality in individuals with and without diabetes, which provided additional information for prognostic prediction and contributed to improving risk stratification.

Non-Abelian Holonomy in Degenerate Non-Hermitian Systems.

Non-Abelian holonomy, a noncommutative process that measures the parallel transport of non-Abelian gauge fields, has so far been realized in degenerate Hermitian systems with degenerate eigenstates or nondegenerate non-Hermitian systems with exceptional points. Here, we introduce non-Abelian holonomy into degenerate non-Hermitian systems possessing degenerate exceptional points and degenerate energy topologies. The interplay between energy degeneracy and energy topology around exceptional points leads to a non-Abelian holonomy with multiple energy levels and multiple degenerate levels simultaneously, going beyond that in degenerate Hermitian systems with a single energy level, or in nondegenerate non-Hermitian systems with a single degenerate level. We exploit an on-chip photonic platform to experimentally demonstrate the holonomy induced non-Abelian phenomenon, including the switching of eigenstates associated with different degenerate exceptional points and sequence-dependent holonomic outcomes. Our work shifts the paradigm of non-Abelian holonomy and adds new degrees of freedom for non-Abelian applications.

Intercalation of Al3+ into Prussian Blue Analogues from Nonaqueous Electrolytes.

Nonaqueous aluminum-ion batteries (AIBs) provide advantages, such as high energy density, enhanced safety, and reduced corrosion, making them ideal for advanced energy storage solutions. A key challenge faced by AIBs is the lack of suitable cathode materials for rapid Al-ion insertion /extraction. Herein, K2Mn[Fe(CN)6] 2H2O (KMHCF) is innovatively chosen as a model to investigate the aluminum storage performance of Prussian blue analogues in nonaqueous AIBs. As anticipated, the KMHCF allows for reversible aluminum storage and exhibits characteristic charge/discharge plateaus. Furthermore, carbon combined highly crystalline KMHCF (HC-KMHCF@C) is synthesized through a chelator-assisted preparation method in combination with an in situ carbon compositing technique. With reduced [Fe(CN)6]4⁻ defects, lower interstitial water content, and enhanced conductivity, HC-KMHCF@C exhibits a high aluminum storage capacity (146.2 mAh g⁻¹ at 0.5 A g⁻¹) and satisfactory cycling performance (maintaining 86.4 mAh g⁻¹ after 800 cycles). The electrochemical reaction mechanism of HC-KMHCF@C is investigated in detail. During the initial charge, K⁺ ions are extracted, shifting the structure from monoclinic to cubic. In subsequent cycles, reversible Al3+ insertion and extraction cause the structure to alternate between monoclinic and cubic phases.

Jiawei Bai-Hu-decoction ameliorated heat stroke-induced brain injury by inhibiting TLR4/NF-κB signal and mitophagy of glial cell.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiawei Bai-Hu-Decoction (JWBHD), a prescription formulated with seven traditional Chinese medicinal material has demonstrated clinical efficacy in mitigating brain injury among heat stroke (HS) patients. AIM OF THE STUDY: This study aimed to evaluate the therapeutic efficacy of JWBHD on rat model of HS and to explore its therapeutic mechanisms by integrating network pharmacology and pharmacodynamic methodologies, which major components were analyzed by using UPLC-MS/MS. MATERIALS AND METHODS: The network pharmacology analysis was firstly conducted to predict the potential active ingredients and therapeutic targets of JWBHD. The anti-HS effectiveness of JWBHD was then evaluated on rats experienced HS. Rat brain tissues were harvested for a comprehensive array of experiments, including Western blot, PCR, H&E staining, Nissl staining, ELISA, transmission electron microscope, flow cytometry and immunofluorescence to validate the protective effects of JWBHD against HS-induced brain damage. Furthermore, the inhibitory effects of JWBHD on TLR4/NF-κB signal and mitophagy of glial were further verified on HS-challenged F98 cell line. Finally, the chemical compositions of the water extract of JWBHD were analyzed by using UPLC-MS/MS. RESULTS: Network pharmacology has identified fifty core targets and numerous HS-related signaling pathways as potential therapeutic targets of JWBHD. Analysis of protein-protein interaction (PPI) and GO suggests that JWBHD may suppress HS-induced inflammatory signals. In experiments conducted on HS-rats, JWBHD significantly reduced the core temperature, restored blood pressure and alleviated neurological defect. Furthermore, JWBHD downregulated the counts of white blood cells and monocytes, decreased the levels of inflammatory cytokines such as IL-1ß, IL-6 and TNF-α in peripheral blood, and suppressed the expression of TLR4 and NF-κB in the cerebral cortex of HS-rats. Besides, JWBHD inhibited the apoptosis of cortical cells and mitigated the damage to the cerebral cortex in HS group. Conversely, overactive mitophagy was observed in the cerebral cortex of HS-rats. However, JWBHD restored the mitochondrial membrane potential and downregulated expressions of mitophagic proteins including Pink1, Parkin, LC3B and Tom20. JWBHD reduced the co-localization of Pink1 and GFAP, a specific marker of astrocytes in the cerebral cortex of HS-rats. In addition, the inhibitory effect of JWBHD on TLR4/NF-κB signaling and overactive mitophagy were further confirmed in F98 cells. Finally, UPLC-MS/MS analysis showed that the main components of JWBHD include isoliquiritigenin, liquiritin, dipotassium glycyrrhizinate, ginsenoside Rb1, ginsenoside Re, etc. CONCLUSIONS: JWBHD protected rats from HS and prevented HS-induced damage in the cerebral cortex by suppressing TLR4/NF-κB signaling and mitophagy of glial.

Contribution of inwardly rectifying potassium channel 4.1 in orofacial neuropathic pain: Regulation of pannexin 3 via the reactive oxygen species-activated P38 MAPK signal pathway.

The involvement of inwardly rectifying potassium channel 4.1 (Kir4.1) in neuropathic pain has been established. However, there is limited understanding of the downstream mechanism through which Kir4.1 contributes to orofacial neuropathic pain. The objective of this study was to examine the regulation of Kir4.1 on the expression of pannexin 3 (Panx3) in the trigeminal ganglion (TG) and the underlying mechanism in the context of orofacial neuropathic pain caused by chronic constriction injury of the infraorbital nerve (CCI-ION). The study observed a significant increase in Panx3 expression in the TG of mice with CCI-ION. Inhibition of Panx3 in the TG of CCI-ION mice resulted in alleviation of orofacial mechanical allodynia. Furthermore, conditional knockdown (CKD) of Kir4.1 in the TG of both male and female mice led to mechanical allodynia and upregulation of Panx3 expression. Conversely, overexpression of Kir4.1 decreased Panx3 levels in the TG and relieved mechanical allodynia in CCI-ION mice. In addition, silencing Kir4.1 in satellite glial cells (SGCs) decreased Panx3 expression and increased the phosphorylation of P38 MAPK. Moreover, silencing Kir4.1 in SGCs increased the levels of reactive oxygen species (ROS). The elevated phosphorylation of P38 MAPK resulting from Kir4.1 silencing was inhibited by using a superoxide scavenger known as the tempol. Silencing Panx3 in the TG in vivo attenuated the mechanical allodynia caused by Kir4.1 CKD. In conclusion, these findings suggest that the reduction of Kir4.1 promotes the expression of Panx3 by activating the ROS-P38 MAPK signalling pathway, thus contributing to the development of orofacial neuropathic pain.

Bowtie Nanoantenna LSPR Biosensor for Early Prediction of Preeclampsia.

OBJECTIVE: The concentration of the placental circulating factor in early pregnancy is often extremely low, and the traditional prediction method cannot meet the clinical demand for early detection preeclampsia in high-risk gravida. It is of prime importance to seek an ultra-sensitive early prediction method. METHODS: In this study, finite-different time-domain (FDTD) and Discrete Dipole Approximation (DDA) simulation, and electron beam lithography (EBL) methods were used to develop a bowtie nanoantenna (BNA) with the best field enhancement and maximum coupling efficiency. Bio-modification of the placental circulating factor (sFlt-1, PLGF) to the noble nanoparticles based on the amino coupling method were explored. A BNA LSPR biosensor which can specifically identify the placental circulating factor in preeclampsia was constructed. RESULTS: The BNA LSPR biosensor can detect serum placental circulating factors without toxic labeling. Serum sFlt-1 extinction signal (Δλmax) in the preeclampsia group was higher than that in the normal pregnancy group (14.37 ± 2.56 nm vs. 4.21 ± 1.36 nm), p = 0.008, while the serum PLGF extinction signal in the preeclampsia group was lower than that in the normal pregnancy group (5.36 ± 3.15 nm vs. 11.47 ± 4.92 nm), p = 0.013. The LSPR biosensor detection results were linearly consistent with the ELISA kit. CONCLUSIONS: LSPR biosensor based on BNA can identify the serum placental circulating factor of preeclampsia with high sensitivity, without toxic labeling and with simple operation, and it is expected to be an early detection method for preeclampsia.

N-methyl-D-aspartate Receptor Subunits 2A and 2B Mediate Connexins and Pannexins in the Trigeminal Ganglion Involved in Orofacial Inflammatory Allodynia during Temporomandibular Joint Inflammation.

Temporomandibular joint osteoarthritis (TMJOA) is a severe form of temporomandibular joint disorders (TMD), and orofacial inflammatory allodynia is one of its common symptoms which lacks effective treatment. N-methyl-D-aspartate receptor (NMDAR), particularly its subtypes GluN2A and GluN2B, along with gap junctions (GJs), are key players in the mediation of inflammatory pain. However, the precise regulatory mechanisms of GluN2A, GluN2B, and GJs in orofacial inflammatory allodynia during TMJ inflammation still remain unclear. Here, we established the TMJ inflammation model by injecting Complete Freund's adjuvant (CFA) into the TMJ and used Cre/loxp site-specific recombination system to conditionally knock out (CKO) GluN2A and GluN2B in the trigeminal ganglion (TG). Von-frey test results indicated that CFA-induced mechanical allodynia in the TMJ region was relieved in GluN2A and GluN2B deficient mice. In vivo, CFA significantly up-regulated the expression of GluN2A and GluN2B, Gjb1, Gjb2, Gjc2 and Panx3 in the TG, and GluN2A and GluN2B CKO played different roles in mediating the expression of Gjb1, Gjb2, Gjc2 and Panx3. In vitro, NMDA up-regulated the expression of Gjb1, Gjb2, Gjc2 and Panx3 in satellite glial cells (SGCs) as well as promoted the intercellular communication between SGCs, and GluN2A and GluN2B knocking down (KD) altered the expression and function differently. NMDAR regulated Gjb1 and Panx3 through ERK1/2 pathway, and mediated Gjb2 and Gjc2 through MAPK, PKA, and PKC intracellular signaling pathways. These findings shed light on the distinct functions of GluN2A and GluN2B in mediating peripheral sensitization induced by TMJ inflammation in the TG, offering potential therapeutic targets for managing orofacial inflammatory allodynia.

Microfluidic Electrochemical Integrated Sensor for Efficient and Sensitive Detection of Candida albicans.

Traditional methods for the detection of pathogenic bacteria are time-consuming, less efficient, and sensitive, which affects infection control and bungles illness. Therefore, developing a method to remedy these problems is very important in the clinic to diagnose the pathogenic diseases and guide the rational use of antibiotics. Here, microfluidic electrochemical integrated sensor (MEIS) has been investigated, functionally for rapid, efficient separation and sensitive detection of pathogenic bacteria. Three-dimensional macroporous PDMS and Au nanotube-based electrode are successfully assembled into the modeling microchip, playing the functions of "3D chaotic flow separator" and "electrochemical detector," respectively. The 3D chaotic flow separator enhances the turbulence of the fluid, achieving an excellent bacteria capture efficiency. Meanwhile, the electrochemical detector provides a quantitative signal through enzyme-linked immunoelectrochemistry with improved sensitivity. The microfluidic electrochemical integrated sensor could successfully isolate Candida albicans (C. albicans) in the range of 30-3,000,000 CFU in the saliva matrix with over 95% capture efficiency and sensitively detect C. albicans in 1 h in oral saliva samples. The integrated device demonstrates great potential in the diagnosis of oral candidiasis and is also applicable in the detection of other pathogenic bacteria.

Nano-Proteolysis Targeting Chimeras (Nano-PROTACs) in Cancer Therapy.

Proteolysis-targeting chimeras (PROTACs) are heterobifunctional molecules that have the capability to induce specific protein degradation. While playing a revolutionary role in effectively degrading the protein of interest (POI), PROTACs encounter certain limitations that impede their clinical translation. These limitations encompass off-target effects, inadequate cell membrane permeability, and the hook effect. The advent of nanotechnology presents a promising avenue to surmount the challenges associated with conventional PROTACs. The utilization of nano-proteolysis targeting chimeras (nano-PROTACs) holds the potential to enhance specific tissue accumulation, augment membrane permeability, and enable controlled release. Consequently, this approach has the capacity to significantly enhance the controllable degradation of target proteins. Additionally, they enable a synergistic effect by combining with other therapeutic strategies. This review comprehensively summarizes the structural basis, advantages, and limitations of PROTACs. Furthermore, it highlights the latest advancements in nanosystems engineered for delivering PROTACs, as well as the development of nano-sized PROTACs employing nanocarriers as linkers. Moreover, it delves into the underlying principles of nanotechnology tailored specifically for PROTACs, alongside the current prospects of clinical research. In conclusion, the integration of nanotechnology into PROTACs harbors vast potential in enhancing the anti-tumor treatment response and expediting clinical translation.

Vertebral HU value and the pectoral muscle index based on chest CT can be used to opportunistically screen for osteoporosis.

BACKGROUND: Existing studies have shown that computed tomography (CT) attenuation and skeletal muscle tissue are strongly associated with osteoporosis; however, few studies have examined whether vertebral HU values and the pectoral muscle index (PMI) measured at the level of the 4th thoracic vertebra (T4) are strongly associated with bone mineral density (BMD). In this study, we demonstrate that vertebral HU values and the PMI based on chest CT can be used to opportunistically screen for osteoporosis and reduce fracture risk through prompt treatment. METHODS: We retrospectively evaluated 1000 patients who underwent chest CT and DXA scans from August 2020-2022. The T4 HU value and PMI were obtained using manual chest CT measurements. The participants were classified into normal, osteopenia, and osteoporosis groups based on the results of dual-energy X-ray (DXA) absorptiometry. We compared the clinical baseline data, T4 HU value, and PMI between the three groups of patients and analyzed the correlation between the T4 HU value, PMI, and BMD to further evaluate the diagnostic efficacy of the T4 HU value and PMI for patients with low BMD and osteoporosis. RESULTS: The study ultimately enrolled 469 participants. The T4 HU value and PMI had a high screening capacity for both low BMD and osteoporosis. The combined diagnostic model-incorporating sex, age, BMI, T4 HU value, and PMI-demonstrated the best diagnostic efficacy, with areas under the receiver operating characteristic curve (AUC) of 0.887 and 0.892 for identifying low BMD and osteoporosis, respectively. CONCLUSIONS: The measurement of T4 HU value and PMI on chest CT can be used as an opportunistic screening tool for osteoporosis with excellent diagnostic efficacy. This approach allows the early prevention of osteoporotic fractures via the timely screening of individuals at high risk of osteoporosis without requiring additional radiation.

Sequentially photocatalytic degradation of mussel-inspired polydopamine: From nanoscale disassembly to effective mineralization.

Mussel-inspired polydopamine (PDA) coating has been utilized extensively as versatile deposition strategies that can functionalize surfaces of virtually all substrates. However, the strong adhesion, stability and intermolecular interaction of PDA make it inefficient in certain applications. Herein, a green and efficient photocatalytic method was reported to remove adhesion and degrade PDA by using TiO2-H2O2 as photocatalyst. The photodegradation process of the PDA spheres was first undergone nanoscale disassembly to form soluble PDA oligomers or well-dispersed nanoparticles. Most of the disassembled PDA can be photodegraded and finally mineralized to CO2 and H2O. Various PDA coated templates and PDA hollow structures can be photodegraded by this strategy. Such process provides a practical strategy for constructing the patterned and gradient surfaces by the "top-down" method under the control of light scope and intensity. This sequential degradation strategy is beneficial to achieve the decomposition of highly crosslinked polymers.

Genome-wide identification, expression analysis of WRKY transcription factors in Citrus ichangensis and functional validation of CiWRKY31 in response to cold stress.

BACKGROUND: Ichang papeda (Citrus ichangensis), a wild perennial plant of the Rutaceae family, is a cold-hardy plant. WRKY transcription factors are crucial regulators of plant growth and development as well as abiotic stress responses. However, the WRKY genes in C. ichangensis (CiWRKY) and their expression patterns under cold stress have not been thoroughly investigated, hindering our understanding of their role in cold tolerance. RESULTS: In this study, a total of 52 CiWRKY genes identified in the genome of C. ichangensis were classified into three main groups and five subgroups based on phylogenetic analysis. Comprehensive analyses of motif features, conserved domains, and gene structures were performed. Segmental duplication plays a significant role in the CiWRKY gene family expansion. Cis-acting element analysis revealed the presence of various stress-responsive elements in the promoters of the majority of CiWRKYs. Gene ontology (GO) analysis and protein-protein interaction predictions indicate that the CiWRKYs exhibit crucial roles in regulation of both development and stress response. Expression profiling analysis demonstrates that 14 CiWRKYs were substantially induced under cold stress. Virus-induced gene silencing (VIGS) assay confirmed that CiWRKY31, one of the cold-induced WRKYs, functions positively in regulation of cold tolerance. CONCLUSION: Sequence and protein properties of CiWRKYs were systematically analyzed. Among the 52 CiWRKY genes 14 members exhibited cold-responsive expression patterns, and CiWRKY31 was verified to be a positive regulator of cold tolerance. These findings pave way for future investigations to understand the molecular functions of CiWRKYs in cold tolerance and contribute to unravelling WRKYs that may be used for engineering cold tolerance in citrus.

Smart Microneedle Arrays Integrating Cell-Free Therapy and Nanocatalysis to Treat Liver Fibrosis.

Liver fibrosis is a chronic pathological condition lacking specific clinical treatments. Stem cells, with notable potential in regenerative medicine, offer promise in treating liver fibrosis. However, stem cell therapy is hindered by potential immunological rejection, carcinogenesis risk, efficacy variation, and high cost. Stem cell secretome-based cell-free therapy offers potential solutions to address these challenges, but it is limited by low delivery efficiency and rapid clearance. Herein, an innovative approach for in situ implantation of smart microneedle (MN) arrays enabling precisely controlled delivery of multiple therapeutic agents directly into fibrotic liver tissues is developed. By integrating cell-free and platinum-based nanocatalytic combination therapy, the MN arrays can deactivate hepatic stellate cells. Moreover, they promote excessive extracellular matrix degradation by more than 75%, approaching normal levels. Additionally, the smart MN arrays can provide hepatocyte protection while reducing inflammation levels by ≈70-90%. They can also exhibit remarkable capability in scavenging almost 100% of reactive oxygen species and alleviating hypoxia. Ultimately, this treatment strategy can effectively restrain fibrosis progression. The comprehensive in vitro and in vivo experiments, supplemented by proteome and transcriptome analyses, substantiate the effectiveness of the approach in treating liver fibrosis, holding immense promise for clinical applications.

Lipids, apolipoproteins and gestational diabetes mellitus: a Mendelian randomization study.

BACKGROUND: This study investigates the causal relationship between lipid traits and GDM in an effort to better understand the aetiology of GDM. METHODS: Employing a two-sample Mendelian Randomization (MR) framework, we used Single Nucleotide Polymorphisms (SNPs) as instrumental variables to examine the impact of lipids and apolipoproteins on GDM. The research comprised univariable and multivariable MR analyses, with a prime focus on individual and combined effects of lipid-related traits. Statistical techniques included the fixed-effect inverse variance weighted (IVW) method and supplementary methods such as MR-Egger for comprehensive assessment. RESULTS: Our findings revealed the following significant associations: apoA-I and HDL cholesterol were inversely correlated with GDM risk, while triglycerides showed a positive correlation. In multivariable analysis, apoA-I consistently exhibited a strong causal link with GDM, even after adjusting for other lipids and Body Mass Index (BMI). CONCLUSION: The study demonstrates a significant causal relationship between apoA-I and GDM risk.