Novel insight into astrocyte-mediated gliotransmission modulates the synaptic plasticity in major depressive disorder.

Major depressive disorder (MDD) is a form of glial cell-based synaptic dysfunction disease in which glial cells interact closely with neuronal synapses and perform synaptic information processing. Glial cells, particularly astrocytes, are active components of the brain and are responsible for synaptic activity through the release gliotransmitters. A reduced density of astrocytes and astrocyte dysfunction have both been identified the brains of patients with MDD. Furthermore, gliotransmission, i.e., active information transfer mediated by gliotransmitters between astrocytes and neurons, is thought to be involved in the pathogenesis of MDD. However, the mechanism by which astrocyte-mediated gliotransmission contributes to depression remains unknown. This review therefore summarizes the alterations in astrocytes in MDD, including astrocyte marker, connexin 43 (Cx43) expression, Cx43 gap junctions, and Cx43 hemichannels, and describes the regulatory mechanisms of astrocytes involved in synaptic plasticity. Additionally, we investigate the mechanisms acting of the glutamatergic, gamma-aminobutyric acidergic, and purinergic systems that modulate synaptic function and the antidepressant mechanisms of the related receptor antagonists. Further, we summarize the roles of glutamate, gamma-aminobutyric acid, d-serine, and adenosine triphosphate in depression, providing a basis for the identification of diagnostic and therapeutic targets for MDD.

Transcriptome analysis of the diseased intervertebral disc tissue in patients with spinal tuberculosis.

OBJECTIVE: To investigate the differential expression genes (DEGs) in spinal tuberculosis using transcriptomics, with the aim of identifying novel therapeutic targets and prognostic indicators for the clinical management of spinal tuberculosis. METHODS: Patients who visited the Department of Orthopedics at the Second Hospital, Lanzhou University from January 2021 to May 2023 were enrolled. Based on the inclusion and exclusion criteria, there were 5 patients in the test group and 5 patients in the control group. Total RNA was extracted and paired-end sequencing was conducted on the sequencing platform. After processing the sequencing data with clean reads and annotating the reference genome, FPKM normalization and differential expression analysis were performed. The DEGs and long non-coding RNAs (LncRNAs) were analyzed for Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment. The cis-regulation of differentially expressed mRNAs (DE mRNAs) by LncRNAs was predicted and analyzed to establish a co-expression network. RESULTS: This study identified 2366 DEGs, with 974 genes significantly upregulated and 1392 genes significantly downregulated. The upregulated genes are associated with cytokine-cytokine receptor interactions, tuberculosis, and TNF-α signaling pathways, primarily enriched in biological processes such as immunity and inflammation. The downregulated genes are related to muscle development, contraction, fungal defense response, and collagen metabolism processes. Analysis of LncRNAs from bone tuberculosis RNA-seq data detected a total of 3652 LncRNAs, with 356 significantly upregulated and 184 significantly downregulated. Further analysis identified 311 significantly different LncRNAs that could cis-regulate 777 target genes, enriched in pathways such as muscle contraction, inflammatory response, and immune response, closely related to bone tuberculosis. There are 51 genes enriched in the immune response pathway regulated by cis-acting LncRNAs. LncRNAs that regulate immune response-related genes, such as upregulated RP11-451G4.2, RP11-701P16.5, AC079767.4, AC017002.1, LINC01094, CTA-384D8.35, and AC092484.1, as well as downregulated RP11-2C24.7, may serve as potential prognostic and therapeutic targets. CONCLUSION: The DE mRNAs and LncRNAs in spinal tuberculosis are both associated with immune regulatory pathways. These pathways promote or inhibit the tuberculosis infection and development at the mechanistic level and play an important role in the process of tuberculosis transferring to bone tissue.

Endoscopic ultrasound-guided treatment of isolated gastric varices entwined with arteries: A case report.

BACKGROUND: Interventional endoscopic ultrasound is clinically used for the treatment of isolated gastric varices (IGVs) owing to its precise visualization. CASE SUMMARY: A 39-year-old man was diagnosed with a large IGV during a routine physical examination. Endoscopic ultrasonography showed gastric varices entwined with an artery, which greatly increased the difficulty of treatment. We successfully treated the patient with endoscopic ultrasonography-guided coil embolization combined with cyanoacrylate injection. CONCLUSION: Endoscopic ultrasonography-guided coil embolization combined with cyanoacrylate injection was safe and effective for the treatment of an IGV entwined with an artery.

Chemical Structure Evolution of Thermally Altered Coal during the Preparation of Coal-Based Graphene and Division of Thermally Altered Zone: Based on FTIR and Raman.

A suite of coal samples near a diabase dike was collected to investigate the structural and functional group evolution of a series of carbon materials prepared from thermally altered coals, explore the influence of thermal metamorphism distance on the structure of coal and its carbon material products, and divide the thermally altered zones. Using Fourier transform infrared and Raman studies, it was found that after demineralization, the aromatic parameters f ar H and I of the coal structure slightly increase, while the aliphatic parameters CH2/CH3 and oxidation parameter 'C' slightly decrease, and the degree of order of the coal structure increases. Graphitization can greatly improve aromatic parameters, eliminate aliphatic structures, and enhance orderliness. However, after oxidation and reduction, the aromatic parameters and ordering degree of graphene decrease. Except for the sample closely attached to the dike, the coal-based graphene yield of the other samples first decreases and then stabilizes with the increase of distance from the dike, which is consistent with the trend of changes in the reflectance of raw coal. The thermally altered distance affects the structural changes of coal and carbon material products. The coal attached to the dike has been damaged and polluted, and the aromaticity and orderliness of the prepared carbon material products are relatively poor. The aromaticity and orderliness of coal-based products prepared from other thermally altered coals are relatively high and increase with the closer the thermally altered distance. Based on the characterized parameters of coal samples and products with distance from the dike, the sampling area is divided into four zones, including abnormally altered zone, normal altered zone, transition zone, and original coal zone. Among them, the yield and quality of coal-based graphene prepared from coal in the normal altered zone are the highest, an ideal raw material collection area for making coal-based graphene.

Nanocrystalline copper for direct copper-to-copper bonding with improved cross-interface formation at low thermal budget.

Direct copper-to-copper (Cu-Cu) bonding is a promising technology for advanced electronic packaging. Nanocrystalline (NC) Cu receives increasing attention due to its unique ability to promote grain growth across the bonding interface. However, achieving sufficient grain growth still requires a high thermal budget. This study explores how reducing grain size and controlling impurity concentration in NC Cu leads to substantial grain growth at low temperatures. The fabricated NC Cu has a uniform nanograin size of around 50 nm and a low impurity level of 300 ppm. To prevent ungrown NC and void formation caused by impurity aggregation, we propose a double-layer (DL) structure comprising a normal coarse-grained (CG) layer underneath the NC layer. The CG layer, with a grain size of 1 µm and an impurity level of 3 ppm, acts as a sink, facilitating impurity diffusion from the NC layer to the CG layer. Thanks to sufficient grain growth throughout the entire NC layer, cross-interface Cu-Cu bonding becomes possible under a low thermal budget, either at 100 °C for 60 min or at 200 °C for only 5 min.

Altered structural network in temporal lobe epilepsy with focal to bilateral tonic-clonic seizures.

OBJECTIVES: This study aims to investigate whether alterations in white matter topological networks are associated with focal to bilateral tonic-clonic seizures (FBTCS) in temporal lobe epilepsy (TLE). Additionally, we investigated the variables contributing to memory impairment in TLE. METHODS: This cross-sectional study included 88 unilateral people with TLE (45 left/43 right), and 42 healthy controls. Graph theory analysis was employed to compare the FBTCS (+) group (n = 51) with the FBTCS (-) group (n = 37). The FBTCS (+) group was subcategorized into current-FBTCS (n = 31) and remote-FBTCS (n = 20), based on the history of FBTCS within 1 year or longer than 1 year before scanning, respectively. We evaluated the discriminatory power of topological network properties by receiver operating characteristic (ROC) analysis. Generalized linear models (GLMs) were employed to investigate variables associated with memory impairment in TLE. RESULTS: Global efficiency (Eg) was significantly reduced in the FBTCS (+) group, especially in the current-FBTCS subgroup. Greater disruption of regional properties in the ipsilateral occipital and temporal association cortices was observed in the FBTCS (+) group. ROC analysis revealed that Eg, normalized characteristic shortest path length, and nodal efficiency of the ipsilateral middle temporal gyrus could distinguish between FBTCS (+) and FBTCS (-) groups. Additionally, GLMs linked the occurrence of current FBTCS with poorer verbal memory outcomes in TLE. INTERPRETATION: Our study suggests that abnormal networks could be the structural basis of seizure propagation in FBTCS. Strategies aimed at reducing the occurrence of FBTCS could potentially improve the memory outcomes in people with TLE.

Acupuncture for clinical improvement of endometriosis-related pain: a systematic review and meta-analysis.

BACKGROUND: Endometriosis is a common chronic gynecological condition characterized by the presence of endometrial tissue outside the uterine cavity, leading to chronic inflammation, pelvic nodules and masses, pelvic pain, and infertility. Acupuncture has been shown to improve pain associated with endometriosis by modulating abnormal levels of prostaglandins, ß-endorphins, dynorphins, electrolytes, and substance P. This review aims to evaluate the clinical efficacy of acupuncture in treating endometriosis, specifically focusing on its efficacy in relieving pain associated with endometriosis. METHODS: A comprehensive search was conducted in eight databases (PubMed, EMBASE, Cochrane, Web of Science, China National Knowledge Infrastructure (CNKI), the China Biology Medicine (CBM), Wanfang, and Weipu database) to identify randomized controlled trials (RCTs) published from database inception to December 16, 2022, which investigated the use of acupuncture for endometriosis-related pain. Two researchers independently screened articles, extracted data, and assessed methodological quality using the Cochrane Collaboration's risk of bias tool. Meta-analysis was performed using Stata statistical software. RESULTS: A total of 1991 articles were identified, and ultimately, 14 studies involving 793 patients (387 in the acupuncture group and 359 in the control group) were included. The control interventions in the included studies included placebo, traditional Chinese medicine (TCM), and Western medicine treatments. Meta-analysis results showed that compared to the control group, acupuncture treatment for pain associated with endometriosis demonstrated significant reductions in pain severity [SMD = - 1.10, 95% CI (- 1.45, - 0.75), P < 0.001], improved response rate [RR = 1.25, 95% CI (1.09, 1.44), P = 0.02], and decreased serum CA-125 levels [SMD = - 0.62, 95% CI (- 1.15, - 0.08), P = 0.024]. Furthermore, subgroup analysis revealed that electroacupuncture and auricular acupuncture were superior to the control group in reducing pain severity, while auricular acupuncture and warm needling showed greater clinical efficacy compared to the control group. However, there were no significant differences between electroacupuncture or fire needling and the control group in terms of pain relief. The findings suggest that acupuncture is effective in improving pain associated with endometriosis. CONCLUSIONS: In conclusion, acupuncture is effective in alleviating dysmenorrhea and pelvic pain associated with endometriosis, reducing serum CA-125 levels, decreasing the size of nodules, improving patients' quality of life, and lowering the recurrence rate. However, it should be noted that the current evidence is limited by the design and quality flaws of the original studies, as well as a lack of research specifically focusing on subtypes of acupuncture. Therefore, caution should be exercised when interpreting the results.

Dependence of the formation kinetics of carbon dioxide hydrate on clay aging for solid carbon dioxide storage.

Clay-based marine sediments have great potential for safe and effective carbon dioxide (CO2) encapsulation by storing enormous amounts of CO2 in solid gas hydrate form. However, the aging of clay with time changes the surface properties of clay and complicates the CO2 hydrate formation behaviors in sediments. Due to the long clay aging period, it is difficult to identify the role of clay aging in the formation of CO2 hydrate in marine sediments. Here, we used ultrasonication and plasma treatment to simulate the breakage and oxidation of clay nanoflakes in aging and investigated the influence of clay aging on CO2 hydrate formation kinetics. We found that the breakage and oxidation of clay nanoflakes would disrupt the siloxane rings and graft hydroxyl on the clay nanoflakes. This decreased the negative charge density of clay nanoflakes and weakened the interfacial interaction of clay nanoflakes with the surrounding water. Therefore, the small clay nanoflakes enriched in hydroxyl would disrupt the surrounding tetrahedral water structure analogous to the CO2 hydrate, resulting in the prolongation of CO2 hydrate nucleation. These results revealed the influence of the structure-function relationship of clay nanoflakes with CO2 hydrate formation and are favorable for the development of hydrate-based CO2 storage.

Development of a Preoperative Prediction Model Based on Spectral CT to Evaluate Axillary Lymph Node With Macrometastases in Clinical T1/2N0 Invasive Breast Cancer.

OBJECTIVES: To develop a prediction model based on spectral computed tomography (CT) to evaluate axillary lymph node (ALN) with macrometastases in clinical T1/2N0 invasive breast cancer. METHODS: A total of 217 clinical T1/2N0 invasive breast cancer patients who underwent spectral CT scans were retrospectively enrolled and categorized into a training cohort (n = 151) and validation cohort (n = 66). These patients were classified into ALN nonmacrometastases (stage pN0 or pN0 [i+] or pN1mi) and ALN macrometastases (stage pN1-3) subgroups. The morphologic criteria and quantitative spectral CT parameters of the most suspicious ALN were measured and compared. Least absolute shrinkage and selection operator (Lasso) was used to screen predictive indicators to build a logistic model. The receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to evaluate the models. RESULTS: The combined arterial-venous phase spectral CT model yielded the best diagnostic performance in discrimination of ALN nonmacrometastases and ALN macrometastases with the highest AUC (0.963 in the training cohort and 0.945 in validation cohorts). Among single phase spectral CT models, the venous phase spectral CT model showed the best performance (AUC = 0.960 in the training cohort and 0.940 in validation cohorts). There was no significant difference in AUCs among the 3 models (DeLong test, P > .05 for each comparison). CONCLUSION: A Lasso-logistic model that combined morphologic features and quantitative spectral CT parameters based on contrast-enhanced spectral imaging potentially be used as a noninvasive tool for individual preoperative prediction of ALN status in clinical T1/2N0 invasive breast cancers.

Biological Evaluation of Lysionotin: a Novel Inhibitor of 5-Lipoxygenase for Anti-glioma.

OBJECTIVE: To explore the potential mechanism of lysionotin in treating glioma. METHODS: First, target prediction based on Bernoulli Naïve Bayes profiling and pathway enrichment was used to predict the biological activity of lysionotin. The binding between 5-lipoxygenase (5-LO) and lysionotin was detected by surface plasmon resonance (SPR) and molecular docking, and the inhibitory effects of lysionotin on 5-LO and proliferation of glioma were determined using enzyme inhibition assay in vitro and cell viability analysis, respectively. Furthermore, the pharmaceutical effect of lysionotin was explored by cell survival rate analysis and liquid chromatography with tandem mass spectrometry (LC-MS/MS). The protein expression, intracellular calcium ion concentration and cytoskeleton detection were revealed by Western blot, flow cytometry and fluorescence labeling, respectively. RESULTS: Target prediction and pathway enrichment revealed that lysionotin inhibited 5-LO, a key enzyme involved in the arachidonic acid metabolism pathway, to inhibit the proliferation of glioma. Molecular docking results demonstrated that 5-LO can be binding to lysionotin through hydrogen bonds, forming bonds with His600, Gln557, Asn554, and His372. SPR analysis further confirmed the interaction between 5-LO and lysionotin. Furthermore, enzyme inhibition assay in vitro and cell survival rate analysis revealed that 50% inhibition concentration of lysionotin and the median effective concentration of lysionotin were 90 and 16.58 µmol/L, respectively, and the results of LC-MS/MS showed that lysionotin inhibited the production of 5S-hydroperoxy-eicosatetraenoic acid (P<0.05), and moreover, the LC-MS/MS results indicated that lysionotin can enter glioma cells well (P<0.01) and inhibit their proliferation. Western blot analysis demonstrated that lysionotin can inhibit the expression of 5-LO (P<0.05) and downstream leukotriene B4 receptor (P<0.01). In addition, the results showed that lysionotin affected intracellular calcium ion concentration by inhibiting 5-LO to affect the cytoskeleton, as determined by flow cytometry and fluorescence labeling. CONCLUSION: Lysionotin binds to 5-LO could suppress glioma by inhibiting arachiodonic acid metabolism pathway.

Total triterpenoids from apple peels exert pronounced anti-breast-cancer activity in vivo and in vitro.

BACKGROUND: Apples are among the most nutritionally valuable fruits and have a history of use in traditional Chinese medicine. Triterpenoids, the primary bioactive compounds found in apples, demonstrate significant antitumor activity. RESULTS: Following enrichment and optimization, the total content of major triterpenoids in total triterpenoids from apple peels (ATT) reached 5.76 g kg-1. The growth of MDA-MB-231 xenograft tumors was significantly inhibited after treatment with ATT. Network pharmacology analysis conclusively identified a close association between the antitumor effect of ATT and the phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) signaling pathway. Experimental validation using MDA-MB-231 cells and a xenograft nude mouse model confirmed that ATT suppressed tumor cell proliferation effectively by modulating the PI3K-Akt signaling pathway, which was consistent with the findings from network pharmacology. The total triterpenoids from apple peels also induced cell apoptosis by mediating the PI3K-Akt signaling pathway. CONCLUSION: The total triterpenoids from apple peels can inhibit tumor cell proliferation and induce cell apoptosis effectively through the PI3K-Akt signaling pathway, suggesting that ATT holds promise as a prospective therapeutic agent for breast cancer treatment. © 2024 Society of Chemical Industry.

Bone volume and height changes for lateral window sinus floor elevation using two types of deproteinized bovine bone mineral: A retrospective cohort study of 1-4 years.

OBJECTIVE: To compare bone volume and height changes of two types of deproteinized bovine bone mineral (DBBM) for lateral window sinus floor elevation (LSFE) with simultaneous implant placement. MATERIALS AND METHODS: This retrospective cohort study involved 72 patients who underwent LSFE using low-temperature sintered cancellous bone-derived DBBM (C-DBBM) or high-temperature two-step sintered epiphyseal-derived DBBM (E-DBBM). Cone-beam computed tomography (CBCT) was acquired preoperatively, immediately postoperatively, 6 months and 1-4 years post-surgery. Bone volume (BV), apical bone height (ABH), endo-sinus bone gain (ESBG), and crestal bone level (CBL) were evaluated through three-dimensional fitting and superimposition. Linear mixed models (LMM) were employed to analyze factors influencing the reduction of BV (ΔBV) and ESBG (ΔESBG). RESULTS: The E-DBBM group showed no significant change in BV 1-4 years post-surgery, while the C-DBBM group demonstrated a significant reduction (p = .006) with volume stability of 85.86%. Bone height in the E-DBBM group increased at 6 months and subsequently decreased at 1-4 years (p = .003). In the C-DBBM group, it decreased at 6 months (p = .014), then further decreased at 1-4 years (p = .001). ΔESBG was lower in the E-DBBM group than the C-DBBM group from immediate postoperative to 1-4 years (p = .009). LMM showed graft material type was the primary factor influencing ΔBV (p = .026) and ΔESBG (p = .003). CONCLUSIONS: Within the limitations of this study, both types of DBBM could achieve favorable clinical outcomes. E-DBBM demonstrated enhanced stability in maintaining bone volume and height.

Decreased AMPK/SIRT1/PDK4 induced by androgen excess inhibits human endometrial stromal cell decidualization in PCOS.

Polycystic ovary syndrome (PCOS) is a complex common endocrine disorder affecting women of reproductive age. Ovulatory dysfunction is recognized as a primary infertile factor, however, even when ovulation is medically induced and restored, PCOS patients continue to experience reduced cumulative pregnancy rates and a higher spontaneous miscarriage rate. Hyperandrogenism, a hallmark feature of PCOS, affects ovarian folliculogenesis, endometrial receptivity, and the establishment and maintenance of pregnancy. Decidualization denotes the transformation that the stromal compart of the endometrium must undergo to accommodate pregnancy, driven by the rising progesterone levels and local cAMP production. However, studies on the impact of hyperandrogenism on decidualization are limited. In this study, we observed that primary endometrial stromal cells from women with PCOS exhibit abnormal responses to progesterone during in vitro decidualization. A high concentration of testosterone inhibits human endometrial stromal cells (HESCs) decidualization. RNA-Seq analysis demonstrated that pyruvate dehydrogenase kinase 4 (PDK4) expression was significantly lower in the endometrium of PCOS patients with hyperandrogenism compared to those without hyperandrogenism. We also characterized that the expression of PDK4 is elevated in the endometrium stroma at the mid-secretory phase. Artificial decidualization could enhance PDK4 expression, while downregulation of PDK4 leads to abnormal decidualization both in vivo and in vitro. Mechanistically, testosterone excess inhibits IGFBP1 and PRL expression, followed by phosphorylating of AMPK that stimulates PDK4 expression. Based on co-immunoprecipitation analysis, we observed an interaction between SIRT1 and PDK4, promoting glycolysis to facilitate decidualization. Restrain of AR activation resumes the AMPK/SIRT1/PDK4 pathway suppressed by testosterone excess, indicating that testosterone primarily acts on decidualization through AR stimulation. Androgen excess in the endometrium inhibits decidualization by disrupting the AMPK/SIRT1/PDK4 signaling pathway. These data demonstrate the critical roles of endometrial PDK4 in regulating decidualization and provide valuable information for understanding the underlying mechanism during decidualization.

Safety and efficacy of baricitinib in steroid-resistant or relapsed immune thrombocytopenia: An open-label pilot study.

Patients with steroid-resistant or relapsed immune thrombocytopenia (ITP) suffer increased bleeding risk and impaired quality of life. Baricitinib, an oral Janus-associated kinases (JAK) inhibitor, could alleviate both innate and adaptive immune disorders without inducing thrombocytopenia in several autoimmune diseases. Accordingly, an open-label, single-arm, phase 2 trial (NCT05446831) was initiated to explore the safety and efficacy of baricitinib in ITP. Eligible patients were adults with primary ITP who were refractory to corticosteroids and at least one subsequent treatment, and had platelet counts below 30 × 109/L at enrolment. Participants received baricitinib 4 mg daily for 6 months. The primary endpoint was durable response at the 6-month follow-up. A total of 35 patients were enrolled. Durable response was achieved in 20 patients (57.1%, 95% confidence interval, 39.9 to 74.4), and initial response in 23 (65.7%) patients. For patients responding to baricitinib, the median time to response was 12 (IQR 6-20) days, and the median peak platelet count was 94 (IQR 72-128) × 109/L. Among the 27 patients undergoing extend observation, 12 (44.4%) remained responsive for a median duration of approximately 20 weeks after baricitinib discontinuation. Adverse events were reported in 11 (31.4%) patients, including infections in 6 (17.1%) patients during the treatment period. Treatment discontinuation due to an adverse event was reported in 2 (5.7%) patients. Evidence from this pilot study suggested that baricitinib might be a novel candidate for the armamentarium of ITP-modifying agents. Future studies are warranted to validate the safety, efficacy, and optimal dosing of baricitinib in patients with ITP.

Towards mixed physical node reservoir computing: light-emitting synaptic reservoir system with dual photoelectric output.

Memristor-based physical reservoir computing holds significant potential for efficiently processing complex spatiotemporal data, which is crucial for advancing artificial intelligence. However, owing to the single physical node mapping characteristic of traditional memristor reservoir computing, it inevitably induces high repeatability of eigenvalues to a certain extent and significantly limits the efficiency and performance of memristor-based reservoir computing for complex tasks. Hence, this work firstly reports an artificial light-emitting synaptic (LES) device with dual photoelectric output for reservoir computing, and a reservoir system with mixed physical nodes is proposed. The system effectively transforms the input signal into two eigenvalue outputs using a mixed physical node reservoir comprising distinct physical quantities, namely optical output with nonlinear optical effects and electrical output with memory characteristics. Unlike previously reported memristor-based reservoir systems, which pursue rich reservoir states in one physical dimension, our mixed physical node reservoir system can obtain reservoir states in two physical dimensions with one input without increasing the number and types of devices. The recognition rate of the artificial light-emitting synaptic reservoir system can achieve 97.22% in MNIST recognition. Furthermore, the recognition task of multichannel images can be realized through the nonlinear mapping of the photoelectric dual reservoir, resulting in a recognition accuracy of 99.25%. The mixed physical node reservoir computing proposed in this work is promising for implementing the development of photoelectric mixed neural networks and material-algorithm collaborative design.

Impact of blade direction on postoperative femoral head varus in PFNA fixed patients: a clinical review and biomechanical research.

Intertrochanteric femur fracture is a common type of osteoporotic fracture in elderly patients, and postoperative femoral head varus following proximal femoral nail anti-rotation (PFNA) fixation is a crucial factor contributing to the deterioration of clinical outcomes. The cross-angle between the implant and bone might influence fixation stability. Although there is a wide range of adjustment in the direction of anti-rotation blades within the femoral neck, the impact of this direct variation on the risk of femoral head varus and its biomechanical mechanisms remain unexplored. In this study, we conducted a retrospective analysis of clinical data from 69 patients with PFNA fixation in our institution. We judge the direction of blade on the femoral neck in on the immediate postoperative lateral X-rays or intraoperative C-arm fluoroscopy, investigating its influence on the early postoperative risk of femoral head varus. p < 0.05 indicates significant results in both correlation and regression analyses. Simultaneously, a three-dimensional finite element model was constructed based on the Syn-Bone standard proximal femur outline, exploring the biomechanical mechanisms of the femoral neck-anti-rotation blade direction variation on the risk of this complication. The results indicated that ventral direction insertion of the anti-rotation blade is an independent risk factor for increased femoral head varus. Complementary biomechanical studies further confirmed that ventral angulation leads to loss of fixation stability and a decrease in fixation failure strength. Therefore, based on this study, it is recommended to avoid ventral directional insertion of the anti-rotation blade in PFNA operation or to adjust it in order to reduce the risk of femoral head varus biomechanically, especially in unstable fractures. This adjustment will help enhance clinical outcomes for patients.

Hierarchical Supramolecular Aggregation of Molecular Nanoparticles for Granular Materials with Ultra High-Speed Impact-Resistance.

The high-speed impact-resistanct materials are of great significance while their development is hindered by the intrinsic tradeoff between mechanical strength and energy dissipation capability. Herein, the new chemical system of molecular granular material (MGM) is developed for the design of impact-resistant materials from the supramolecular complexation of sub-nm molecular clusters (MCs) and hyper-branched polyelectrolytes. Their hierarchical aggregation provides the origin of the decoupling of mechanical strengths and structural relaxation dynamics. The MCs' intrinsic fast dynamics afford excellent high-speed impact-resistance, up to 5600 s-1 impact in a typical split-Hopkinson pressure bar test while only tiny boundary cracks can be observed even under 7200 s-1 impact. The high loadings of MCs and their hierarchical aggregates provide high-density sacrificial bonding for the effective dissipation of the impact energy, enabling the protection of fragile devices from the direct impact of over 200 m s-1 bullet. Moreover, the MGMs can be conveniently processed into protective coatings or films with promising recyclability due to the supramolecular interaction feature. The research not only reveals the unique relaxation dynamics and mechanical properties of MGMs in comparison with polymers and colloids, but also develops new chemical systems for the fabrication of high-speed impact-resistant materials.

Increased adrenal steroidogenesis and suppressed corticosteroid responsiveness in critical COVID-19.

BACKGROUND: The effect of coronavirus disease 2019 (COVID-19) on adrenal endocrine metabolism in critically ill patients remains unclear. This study aimed to investigate the alterations in adrenal steroidogenic activity, elucidate underlying mechanisms, provide in situ histopathological evidence, and examine the clinical implications. METHODS: The comparative analyses of the adrenal cortices from 24 patients with fatal COVID-19 and 20 matched controls was performed, excluding patients previously treated with glucocorticoids. Several SARS-CoV-2 and its receptors were identified and pathological alterations were examined. Furthermore, histological examinations, immunohistochemical staining and ultrastructural analyses were performed to assess corticosteroid biosynthesis. The zona glomerulosa (ZG) and zona fasciculata (ZF) were then dissected for proteomic analyses. The biological processes that affected steroidogenesis were analyzed by integrating histological, proteomic, and clinical data. Finally, the immunoreactivity of mineralocorticoids and glucocorticoid receptors in essential tissues were quantitatively measured to evaluate corticosteroid responsiveness. FINDINGS: The demographic characteristics of COVID-19 patients were comparable with those of controls, excluding those that affected adrenal function. SARS-CoV-2-like particles were identified in the adrenocortical cells of three patients; however, these particles did not affect cellular morphology or steroid synthesis compared with those in SARS-CoV-2-negative specimens. Although the adrenals exhibited focal necrosis, vacuolization, microthrombi, and inflammation, widespread degeneration was not evident. Notably, corticosteroid biosynthesis was significantly enhanced in both the ZG and ZF of COVID-19 patients. The increase in the inflammatory response and cellular differentiation in the adrenal cortices of patients with critical COVID-19 was positively correlated with heightened steroidogenic activity. Additionally, the appearance of more dual-ZG/ZF identity cells in COVID-19 adrenals was in accordance with the increased steroidogenic function. However, activated mineralocorticoid and glucocorticoid receptors in vital tissues were markedly reduced in patients with critical COVID-19. INTERPRETATION: Critical COVID-19 was characterized by potentiated adrenal steroidogenesis, associated with exacerbation of inflammation, differentiation and the presence of dual-ZG/ZF identity cells. These alterations implied the reduced effectiveness of conventional corticosteroid therapy and underscored the need for evaluation of adrenal axis and the corticosteroid sensitivity.

Contribution to energy conservation and quality improvement of frozen pork via contact/contactless immersion freezing in NaCl solution.

High energy consumption and quality deterioration are major challenges in the meat freezing process. In this study, the energy consumption and qualities of frozen pork were investigated using three freezing methods: nonpackaged pork air freezing (NAF), contactless immersion freezing (PIF) and contact immersion freezing (NIF) with NaCl solution as a refrigerant. The results indicated that NIF could improve the energy conservation and freezing efficiency in >4 freezing treatment-times by increasing the unfrozen water content, decreasing the frozen heat load, shortening the freezing time and reducing evaporation loss. NIF could also increase the a* value of the pork and improve the water-holding capacity by facilitating the conversion of free water to immobilized-water. The two immersion freezing methods could reduce freezing-thawing loss and protein loss by alleviating muscle tissue freezing damage. These results provide a suitable application of immersion freezing with energy conservation, high efficiency and good quality of frozen-pork.

Application of optical coherence tomography in cardiovascular diseases: bibliometric and meta-analysis.

Significance: Since the advent of Optical Coherence Tomography (OCT) two decades ago, there has been substantial advancement in our understanding of intravascular biology. Identifying culprit lesion pathology through OCT could precipitate a paradigm shift in the treatment of patients with Acute Coronary Syndrome. Given the technical prowess of OCT in the realm of cardiology, bibliometric analysis can reveal trends and research focal points in the application of OCT for cardiovascular diseases. Concurrently, meta-analyses provide a more comprehensive evidentiary base, supporting the clinical efficacy of OCT-guided Percutaneous Coronary Intervention (PCI). Design: This study employs a dual approach of Bibliometric and Meta-analysis. Methods: Relevant literature from 2003 to 2023 was extracted from the Web of Science Core Collection (WoSCC) and analyzed using VOSviewer, CiteSpace, and R for publication patterns, countries, institutions, authors, and research hotspots. The study compares OCT-guided and coronary angiography-guided PCI in treating adult coronary artery disease through randomized controlled trials (RCTs) and observational studies. The study has been reported in the line with PRISMA and AMSTAR Guidelines. Results: Adhering to inclusion and exclusion criteria, 310 publications were incorporated, demonstrating a continual rise in annual output. Chinese researchers contributed the most studies, while American research wielded greater influence. Analysis of trends indicated that research on OCT and angiography-guided PCI has become a focal topic in recent cohort studies and RCTs. In 11 RCTs (n = 5,277), OCT-guided PCI was not significantly associated with a reduction in the risk of Major Adverse Cardiac Events (MACE) (Odds ratio 0.84, 95% CI 0.65-1.10), cardiac death (0.61, 0.36-1.02), all-cause death (0.7, 0.49-1.02), myocardial infarction (MI) (0.88, 0.69-1.13), target lesion revascularization (TLR) (0.94, 0.7-1.27), target vessel revascularization (TVR) (1.04, 0.76-1.43), or stent thrombosis (0.72, 0.38-1.38). However, in 7 observational studies (n = 4,514), OCT-guided PCI was associated with a reduced risk of MACE (0.66, 0.48-0.91) and TLR (0.39, 0.22-0.68). Conclusion: Our comprehensive review of OCT in cardiovascular disease literature from 2004 to 2023, encompassing country and institutional origins, authors, and publishing journals, suggests that OCT-guided PCI does not demonstrate significant clinical benefits in RCTs. Nevertheless, pooled results from observational studies indicate a reduction in MACE and TLR.