Adverse complications of cervical spinal fusion in patients with different types of diabetes mellitus: A retrospective nationwide inpatient sample database cross-sectional study.

BACKGROUND: Diabetes mellitus (DM) is a prevalent chronic condition that influences spine surgery outcomes. The impact of type Ⅰ and type Ⅱ DM on adverse postoperative outcomes, mortality, prolonged length of stay (LOS), and increased in-hospital costs following cervical fusion surgery remains unclear in the past decade. This study aims to determine the specific effect of different classifications of DM on postoperative complications in patients experiencing cervical fusion surgery. METHOD: Data from the Nationwide Inpatient Sample database was acquired between 2010 and 2019. Patients experiencing cervical fusion were included and classified as having type I DM, type II DM, or neither. Patient demographics, hospital characteristics, operative variables, comorbidities, complications, and other postoperative outcomes were assessed. Propensity score matching analysis was used to balance baseline differences. Univariate and multivariate logistic regression were employed to determine the risk of postoperative outcomes in patients with different classifications of DM. RESULT: A total of 267,174 cervical spinal fusions were identified (224,255 were patients without DM, 670 patients had type I DM, and 42,249 patients had type II DM). After propensity score matching, the multivariate analysis of non-DM and type I DM patients shows significant difference in pneumonia (P=0.020). However, type Ⅱ DM served as an independent predictor of an increased risk of acute cerebrovascular disease (P=0.001), acute myocardial infarction (P=0.014), pneumonia (P=0.045), continuous trauma ventilation (P=0.016), chest pain (P<0.001), urinary tract infection (P<0.001), transfusion (P=0.005) and dysphagia (P=0.013), prolonged LOS (P<0.001) and increased costs (P=0.008). CONCLUSION: Using non-DM patients as a reference, type II DM group demonstrated a higher risk of postoperative complications than type I DM group among patients receiving cervical fusion surgery. This vital distinction could enhance risk stratification and guidance for patients diagnosed with DM before cervical fusion surgery.

A new isoprenyl-phenol-type meroterpenoid from mangrove endophytic fungus Aspergillus sp. GXNU-Y65.

Asperphenol A (1), a new isoprenyl-phenol-type meroterpenoid, was isolated from the mangrove endophytic fungus Aspergillus sp. GXNU-Y65 together with five known compounds (2-6). All structures were assigned using extensive NMR spectroscopic data and electronic circular dichroism (ECD) calculations. Compounds 1-6 were evaluated for their cytotoxic activity against A549 and T24 human cancer cell lines. Among them, compounds 1 and 5 exhibited moderate inhibitory activities against T24 cancer cell lines with the IC50 values of 26.71 and 43.50 µM, respectively.

Interaction between the albumin-bilirubin score and nutritional risk index in the prediction of post-hepatectomy liver failure.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is the most common postoperative complication and the leading cause of death after hepatectomy. The albumin-bilirubin (ALBI) score and nutritional risk index (NRI) have been shown to assess end-stage liver disease and predict PHLF and patient survival. We hypothesized that the ALBI score and NRI interact in the prediction of PHLF. AIM: To analyze the interaction between the ALBI score and NRI in PHLF in patients with hepatocellular carcinoma. METHODS: This retrospective study included 186 patients who underwent hepatectomy for hepatocellular carcinoma at the Affiliated Hospital of Youjiang Medical University for Nationalities between January 2020 and July 2023. Data on patient characteristics and laboratory indices were collected from their medical records. Univariate and multivariate logistic regression were performed to determine the interaction effect between the ALBI score and NRI in PHLF. RESULTS: Of the 186 patients included in the study, PHLF occurred in 44 (23.66%). After adjusting for confounders, multivariate logistic regression identified ALBI grade 2/3 [odds ratio (OR) = 73.713, 95% confidence interval (CI): 9.175-592.199] and NRI > 97.5 (OR = 58.990, 95%CI: 7.337-474.297) as risk factors for PHLF. No multiplicative interaction was observed between the ALBI score and NRI (OR = 0.357, 95%CI: 0.022-5.889). However, the risk of PHLF in patients with ALBI grade 2/3 and NRI < 97.5 was 101 times greater than that in patients with ALBI grade 1 and NRI ≥ 97.5 (95%CI: 56.445-523.839), indicating a significant additive interaction between the ALBI score and NRI in PHLF. CONCLUSION: Both the ALBI score and NRI were risk factors for PHLF, and there was an additive interaction between the ALBI score and NRI in PHLF.

Sesquilignans PD from Zanthoxylum nitidum var. tomentosum exerts antitumor effects via the ROS/MAPK pathway in liver cancer cells.

Sesquilignans PD is a natural phenylpropanoid compound that was isolated from Zanthoxylum nitidum var. tomentosum. In this study, we assessed the antitumor effect of PD on SK-Hep-1 and HepG2 cells and the underlying molecular mechanisms. The results revealed that PD markedly inhibited the proliferation and migration of both liver cancer cells. Moreover, PD induced apoptosis, autophagy, and reactive oxygen species (ROS) production in liver cancer cells. Notably, PD increased the protein levels of p-p38 MAPK and p-ERK1/2 in liver cancer cells. This is the first report on the anticancer effect of PD, which is mediated via increased ROS production and MAPK signaling activation.

Membrane remodeling by FAM92A1 during brain development regulates neuronal morphology, synaptic function, and cognition.

The Bin/Amphiphysin/Rvs (BAR) domain protein FAM92A1 is a multifunctional protein engaged in regulating mitochondrial ultrastructure and ciliogenesis, but its physiological role in the brain remains unclear. Here, we show that FAM92A1 is expressed in neurons starting from embryonic development. FAM92A1 knockout in mice results in altered brain morphology and age-associated cognitive deficits, potentially due to neuronal degeneration and disrupted synaptic plasticity. Specifically, FAM92A1 deficiency impairs diverse neuronal membrane morphology, including the mitochondrial inner membrane, myelin sheath, and synapses, indicating its roles in membrane remodeling and maintenance. By determining the crystal structure of the FAM92A1 BAR domain, combined with atomistic molecular dynamics simulations, we uncover that FAM92A1 interacts with phosphoinositide- and cardiolipin-containing membranes to induce lipid-clustering and membrane curvature. Altogether, these findings reveal the physiological role of FAM92A1 in the brain, highlighting its impact on synaptic plasticity and neural function through the regulation of membrane remodeling and endocytic processes.

Pyruvate dehydrogenase complex E1 subunit α crotonylation modulates cocaine-associated memory through hippocampal neuron activation.

Neuronal activation is required for the formation of drug-associated memory, which is critical for the development, persistence, and relapse of drug addiction. Nevertheless, the metabolic mechanisms underlying energy production for neuronal activation remain poorly understood. In the study, a large-scale proteomics analysis of lysine crotonylation (Kcr), a type of protein posttranslational modification (PTM), reveals that cocaine promoted protein Kcr in the hippocampal dorsal dentate gyrus (dDG). We find that Kcr is predominantly discovered in a few enzymes critical for mitochondrial energy metabolism; in particular, pyruvate dehydrogenase (PDH) complex E1 subunit α (PDHA1) is crotonylated at the lysine 39 (K39) residue through P300 catalysis. Crotonylated PDHA1 promotes pyruvate metabolism by activating PDH to increase ATP production, thus providing energy for hippocampal neuronal activation and promoting cocaine-associated memory recall. Our findings identify Kcr of PDHA1 as a PTM that promotes pyruvate metabolism to enhance neuronal activity for cocaine-associated memory.

Auditory and speech outcomes of cochlear implantation in patients with Waardenburg syndrome: a meta-analysis.

Objective: This study aims to assess the potential efficacy of cochlear implantation as a treatment for patients with Waardenburg syndrome (WS) and to guide clinical work by comparing the effect of auditory and speech recovery after cochlear implantation in patients with WS and non-WS. Methods: PubMed, the Cochrane Library, CNKI, and Wanfang Data were sources for retrieving literature on cochlear implantation in WS, and clinical data meeting the inclusion criteria were meta-analyzed using RevMan5.41. Results: A total of nine articles were included in this study, including 132 patients with WS and 815 patients in the control group. Meta-analysis showed that there are no significant differences in the scores for categories of audit performance (CAP), speech intelligibility rating (SIR), and parents' evaluation of aural/oral performance of children (PEACH) between the WS group and the control group. Conclusion: Cochlear implantation demonstrates comparable auditory and speech recovery outcomes for WS patients and non-WS patients.

Acupuncture and moxibustion treatment for breast cancer-related lymphoedema： a systematic review and Meta-analysis. / é’ˆç¸æ²»ç–—ä¹³è ºç™Œæ·‹å·´æ°´è‚¿çš„ç³»ç»Ÿè¯„ä»·å’ŒMeta分析.

OBJECTIVES: To evaluate the efficacy of acupuncture in treating breast cancer-related lymphedema (BCRL) by using systematic review and Meta analysis method. METHODS: Searching CNKI, Wanfang Data Knowledge Service Platform, VIP Chinese Journal Service Platform, Chinese Biomedical Literature Database, PubMed, Cochrane Library, Embase and Web of Science, the randomized controlled trials (RCTs) literature of acupuncture for BCRL was collected from the establishment of the databases to October 1st, 2023. After data extraction and risk of bias evaluation of the included literature, Meta-analysis was performed using RevMan5.4 software. RESULTS: A total of 14 RCTs with 952 patients were included. The Meta-analysis results showed that compared with comprehensive decongestive therapy (CDT), CDT-associated methods and other interventions of the contro group, acupuncture was able to decrease the circumference of the proximal 10 cm to elbow crease (MD=-1.95, P=0.000 5), reduce the difference in arm circumference (MD=-1.30, P<0.000 01), and increase the effective index (MD=27.47, P<0.000 01；RR=1.23, P=0.000 5)；acupuncture improves the range of motion(ROM) scores of shoulder joint in four areas：anteflexion(SMD=0.47, P=0.04), posterior extension (SMD=0.87, P<0.000 01), abduction (SMD=0.48, P=0.03), and adduction (SMD=0.72, P=0.000 5)；acupuncture also could alleviate pain and improve visual analog scale (VAS) scores (MD=-1.15, P<0.000 01). No serious adverse reactions were reported in the literatures. CONCLUSIONS: Acupuncture can effectively improve the degree of limb edema and subjective symptoms in BCRL patients.

Impact of diabetic kidney disease on post-operative complications after primary elective total hip arthroplasty: a nationwide database analysis.

BACKGROUND: The high prevalence of diabetic kidney disease (DKD) in the United States necessitates further investigation into its impact on complications associated with total hip arthroplasty (THA). This study utilizes a large nationwide database to explore risk factors in DKD cases undergoing THA. METHODS: This research utilized a case-control design, leveraging data from the national inpatient sample for the years 2016 to 2019. Employing propensity score matching (PSM), patients diagnosed with DKD were paired on a 1:1 basis with individuals free of DKD, ensuring equivalent age, sex, race, Elixhauser Comorbidity Index (ECI), and insurance coverage. Subsequently, comparisons were drawn between these PSM-matched cohorts, examining their characteristics and the incidence of post-THA complications. Multivariate logistic regression analysis was then employed to evaluate the risk of early complications after surgery. RESULTS: DKD's prevalence in the THA cohort was 2.38%. A 7-year age gap separated DKD and non-DKD patients (74 vs. 67 years, P < 0.0001). Additionally, individuals aged above 75 exhibited a substantial 22.58% increase in DKD risk (49.16% vs. 26.58%, P < 0.0001). Notably, linear regression analysis yielded a significant association between DKD and postoperative acute kidney injury (AKI), with DKD patients demonstrating 2.274-fold greater odds of AKI in contrast with non-DKD individuals (95% CI: 2.091-2.473). CONCLUSIONS: This study demonstrates that DKD is a significant risk factor for AKI in patients undergoing total hip arthroplasty. Optimizing preoperative kidney function through appropriate interventions might decrease the risk of poor prognosis in this population. More prospective research is warranted to investigate the potential of targeted kidney function improvement strategies in reducing AKI rates after THA. The findings of this study hold promise for enhancing preoperative counseling by surgeons, enabling them to provide DKD patients undergoing THA with more precise information regarding the risks associated with their condition.

Plasma proteome analysis implicates novel proteins as potential therapeutic targets for chronic kidney disease: A proteome-wide association study.

Chronic kidney disease (CKD) is prevalent globally with limited therapeutic drugs available. To systemically identify novel proteins involved in the pathogenesis of CKD and possible therapeutic targets, we integrated human plasma proteomes with the genome-wide association studies (GWASs) of CKD, estimated glomerular filtration rate (eGFR) and blood urea nitrogen (BUN) to perform proteome-wide association study (PWAS), Mendelian Randomization and Bayesian colocalization analyses. The single-cell RNA sequencing data of healthy human and mouse kidneys were analyzed to explore the cell-type specificity of identified genes. Functional enrichment analysis was conducted to investigate the involved signaling pathways. The PWAS identified 22 plasma proteins significantly associated with CKD. Of them, the significant associations of three proteins (INHBC, LMAN2, and SNUPN) were replicated in the GWASs of eGFR, and BUN. Mendelian Randomization analyses showed that INHBC and SNUPN were causally associated with CKD, eGFR, and BUN. The Bayesian colocalization analysis identified shared causal variants for INHBC in CKD, eGFR, and BUN (all PP4 > 0.75). The single-cell RNA sequencing revealed that the INHBC gene was sparsely scattered within the kidney cells. This proteomic study revealed that INHBC, LMAN2, and SNUPN may be involved in the pathogenesis of CKD, which represent novel therapeutic targets and warrant further exploration in future research.

Targeting Adenosine A2b Receptor Promotes Penile Rehabilitation of Refractory Erectile Dysfunction.

The mechanisms of adenosine and specific adenosine receptor subtypes in promoting penile rehabilitation remain unclear. Single-cell RNA sequencing of human corpus cavernosum,  adenosine deaminase (ADA) and adenosine receptors knock-out mice (ADA-/-, A1-/-, A2a-/-, A2b-/-, and A3-/-), and primary corpus cavernosum smooth muscle cells are used to determine receptor subtypes responsible for adenosine-induced erection. Three rat models are established to characterize refractory erectile dysfunction (ED): age-related ED, bilateral cavernous nerve crush related ED (BCNC), and diabetes mellitus-induced ED. In single-cell RNA sequencing data, the corpus cavernosum of ED patients show a decrease in adenosine A1, A2a and A2b receptors. In vivo, A2b receptor knock-out abolishes adenosine-induced erection but not that of A1, A2a, or A3 receptor. Under hypoxic conditions in vitro, activating the A2b receptor increases HIF-1α and decreases PDE5 expression. In refractory ED models, activating the A2b receptor with Bay 60-6583 improves erectile function and down-regulates HIF-1α and TGF-ß. Administering Dipyridamole (40 mg Kg-1) to BCNC rats improve penile adenosine levels and erectile function. Our study reveals that the A2b receptor mediates adenosine-induced penile erection. Activating the A2b receptor promotes penile rehabilitation of refractory ED by alleviating hypoxia and fibrosis.

Manipulation of Cooper-Pair Tunneling via Domain Structure in a van der Waals Ferromagnetic Josephson Junction.

Ferromagnetic Josephson junctions play a key role in understanding the interplay between superconductivity and ferromagnetism in condensed matter physics. The magnetic domain structures of the ferromagnet in such junctions can significantly affect the tunneling of the superconducting Cooper pairs due to the strong interactions between Cooper pairs and local magnetic moments in the ferromagnetic tunnel barrier. However, the underlying microscopic mechanism of relevant quasiparticle tunneling processes with magnetic domain structures remains largely unexplored. Here, the manipulation of Cooper-pair tunneling in the NbSe2/Cr2Ge2Te6/NbSe2 ferromagnetic Josephson junction is demonstrated by using a multidomain ferromagnetic barrier with anisotropic magnetic moments. The evolution of up-, down-magnetized domain and Bloch domain structures in Cr2Ge2Te6 barrier under external magnetic fields leads to the enhancement of the critical tunneling supercurrent and an unconventional dual-peak feature with two local maxima in the field-dependent critical current curve. The phenomenon of magnetic-field-modulated critical tunneling supercurrent can be well explained by the competition between the coherence length of tunneling Cooper pairs and the size of magnetic domain walls in Cr2Ge2Te6 barrier. This kind of ferromagnetic Josephson junction provides an intriguing material system for manipulating Cooper-pair tunneling by tuning the local magnetic moments within magnetic Josephson junction devices.

New Meroterpenoids and α-Pyrone Derivatives Isolated from the Mangrove Endophytic Fungal Strain Aspergillus sp. GXNU-Y85.

Two new meroterpenoids, aspergienynes O and P (1 and 2), one new natural compound, aspergienyne Q (3), and a new α-pyrone derivative named 3-(4-methoxy-2-oxo-2H-pyran-6-yl)butanoic acid (4) were isolated from the mangrove endophytic fungal strain Aspergillus sp. GXNU-Y85, along with five known compounds (5-9). The absolute configurations of those new isolates were confirmed through extensive analysis using spectroscopic data (HRESIMS, NMR, and ECD). The pharmacological study of the anti-proliferation activity indicated that isolates 5 and 9 displayed moderate inhibitory effects against HeLa and A549 cells, with the IC50 values ranging from 16.6 to 45.4 µM.

Uric acid-lowering effect of harpagoside and its protective effect against hyperuricemia-induced renal injury in mice.

Hyperuricemia (HUA) is caused by increased synthesis and/or insufficient excretion of uric acid (UA). Long-lasting HUA may lead to a number of diseases including gout and kidney injury. Harpagoside (Harp) is a bioactive compound with potent anti-inflammatory activity from the roots of Scrophularia ningpoensis. Nevertheless, its potential effect on HUA was not reported. The anti-HUA and nephroprotective effects of Harp on HUA mice were assessed by biochemical and histological analysis. The proteins responsible for UA production and transportation were investigated to figure out its anti-HUA mechanism, while proteins related to NF-κB/NLRP3 pathway were evaluated to reveal its nephroprotective mechanism. The safety was evaluated by testing its effect on body weight and organ coefficients. The results showed that Harp significantly reduced the SUA level and protected the kidney against HUA-induced injury but had no negative effect on safety. Mechanistically, Harp significantly reduced UA production by acting as inhibitors of xanthine oxidase (XOD) and adenosine deaminase (ADA) and decreased UA excretion by acting as activators of ABCG2, OAT1 and inhibitors of GLUT9 and URAT1. Moreover, Harp markedly reduced infiltration of inflammatory cells and down-regulated expressions of TNF-α, NF-κB, NLRP3 and IL-1ß in the kidney. Harp was a promising anti-HUA agent.

Two new withanolides from Physalis minima L.

Two new withanolides named physaminilides L (1) and M (2), together with four known ones (3-6) were isolated from the Physalis minima L. The structures were established by analysis of the HR ESIMS, IR and NMR spectroscopic data. The absolute configurations were determined through NOESY and ECD spectra. For compounds 1-5 assayed at 20 µM and compound 6 at 10 µM, inhibition rates of hepatic fibrosis were 22.19%, 15.29%, 37.07%, 9.27%, 12.45%, and 37.03%, respectively.

Identification of Indicator Genes for Agar Accumulation in Gracilariopsis lemaneiformis (Rhodophyta).

Agar, as a seaweed polysaccharide mainly extracted from Gracilariopsis lemaneiformis, has been commercially applied in multiple fields. To investigate factors indicating the agar accumulation in G. lemaneiformis, the agar content, soluble polysaccharides content, and expression level of 11 genes involved in the agar biosynthesis were analysed under 4 treatments, namely salinity, temperature, and nitrogen and phosphorus concentrations. The salinity exerted the greatest impact on the agar content. Both high (40‱) and low (10‱, 20‱) salinity promoted agar accumulation in G. lemaneiformis by 4.06%, 2.59%, and 3.00%, respectively. The content of agar as a colloidal polysaccharide was more stable than the soluble polysaccharide content under the treatments. No significant correlation was noted between the two polysaccharides, and between the change in the agar content and the relative growth rate of the algae. The expression of all 11 genes was affected by the 4 treatments. Furthermore, in the cultivar 981 with high agar content (21.30 ± 0.95%) compared to that (16.23 ± 1.59%) of the wild diploid, the transcriptional level of 9 genes related to agar biosynthesis was upregulated. Comprehensive analysis of the correlation between agar accumulation and transcriptional level of genes related to agar biosynthesis in different cultivation conditions and different species of G. lemaneiformis, the change in the relative expression level of glucose-6-phosphate isomerase II (gpiII), mannose-6-phosphate isomerase (mpi), mannose-1-phosphate guanylyltransferase (mpg), and galactosyltransferase II (gatII) genes was highly correlated with the relative agar accumulation. This study lays a basis for selecting high-yield agar strains, as well as for targeted breeding, by using gene editing tools in the future.

Superionic fluoride gate dielectrics with low diffusion barrier for two-dimensional electronics.

Exploration of new dielectrics with a large capacitive coupling is an essential topic in modern electronics when conventional dielectrics suffer from the leakage issue near the breakdown limit. Here, to address this looming challenge, we demonstrate that rare-earth metal fluorides with extremely low ion migration barriers can generally exhibit an excellent capacitive coupling over 20 µF cm-2 (with an equivalent oxide thickness of ~0.15 nm and a large effective dielectric constant near 30) and great compatibility with scalable device manufacturing processes. Such a static dielectric capability of superionic fluorides is exemplified by MoS2 transistors exhibiting high on/off current ratios over 108, ultralow subthreshold swing of 65 mV dec-1 and ultralow leakage current density of ~10-6 A cm-2. Therefore, the fluoride-gated logic inverters can achieve notably higher static voltage gain values (surpassing ~167) compared with a conventional dielectric. Furthermore, the application of fluoride gating enables the demonstration of NAND, NOR, AND and OR logic circuits with low static energy consumption. In particular, the superconductor-insulator transition at the clean-limit Bi2Sr2CaCu2O8+δ can also be realized through fluoride gating. Our findings highlight fluoride dielectrics as a pioneering platform for advanced electronic applications and for tailoring emergent electronic states in condensed matter.

Alkaloids from Zanthoxylum nitidum and their anti-proliferative activity against A549 cells by regulating the EGFR/AKT/mTOR pathway.

Zanthoxylum nitidum is frequently used as a traditional Chinese medicine and food supplement. Our previous study revealed that its constituent compounds were able to inhibit cancer cell proliferation. In our continuous exploration of bioactive compounds in Z. nitidum, we isolated ten alkaloids (1-10), including one new natural compound (1), and nine known alkaloids (2-10), from an ethanolic extract of the whole plant. The chemical structures were elucidated based on a combination of comprehensive NMR and HRESIMS analyses. Compounds 5, 8 and 10 exhibited significant antiproliferative effects against A549 cancer cell lines. We further elucidated the underlying molecular mechanisms of the antiproliferative activity of compound 8 in A549 human lung cancer cells. Compound 8 was found to induce cell cycle arrest in the G0/G1 phase via p53 activation and CDK4/6 suppression. Compound 8 also effectively inhibited cell migration through the modulation of the epithelial-mesenchymal transition (EMT), as indicated by the expression of biomarkers, such as N-cadherin downregulation and E-cadherin upregulation. Compound 8 significantly suppressed the activation of the EGFR/AKT/mTOR signalling pathway in A549 cells. These results indicate that alkaloid 8 from Z. nitidum has potential to be a lead antiproliferative compound in cancer cells.

A high-throughput differential scanning fluorimetry method for rapid detection of thermal stability and iron saturation in lactoferrin.

Thermal stability and iron saturation of lactoferrin (LF) are of great significance not only for the evaluation of the biological activities of LF but also for the optimization of the isolation and drying process parameters. Differential scanning calorimetry (DSC) is a well-established and efficient method for thermal stability and iron saturation detection in LF. However, multiple DSC measurements are typically performed sequentially, thus time-consuming and low throughput. Herein, we introduced the differential scanning fluorimetry (DSF) approach to overcome such limitations. The DSF can monitor LF thermal unfolding with a commonly available real-time PCR instrument and a fluorescent dye (SYPRO orange or Glomelt), and the measured melting temperature of LF is consistent with that determined by DSC. On the basis of that, a new quantification method was established for determination of iron saturation levels using the linear correlation of the degree of ion saturation of LF with DSF measurements. Such DSF method is simple, inexpensive, rapid (<15 min), and high throughput (>96 samples per experiment), and provides a valuable alternative tool for thermal stability detection of LF and other whey proteins.