Vacancy-Driven High-Performance Metabolic Assay for Diagnosis and Therapeutic Evaluation of Depression.

Depression is one of the most common mental illnesses and is a well-known risk factor for suicide, characterized by low overall efficacy (<50%) and high relapse rate (40%). A rapid and objective approach for screening and prognosis of depression is highly desirable but still awaits further development. Herein, a high-performance metabolite-based assay to aid the diagnosis and therapeutic evaluation of depression by developing a vacancy-engineered cobalt oxide (Vo-Co3O4) assisted laser desorption/ionization mass spectrometer platform is presented. The easy-prepared nanoparticles with optimal vacancy achieve a considerable signal enhancement, characterized by favorable charge transfer and increased photothermal conversion. The optimized Vo-Co3O4 allows for a direct and robust record of plasma metabolic fingerprints (PMFs). Through machine learning of PMFs, high-performance depression diagnosis is achieved, with the areas under the curve (AUC) of 0.941-0.980 and an accuracy of over 92%. Furthermore, a simplified diagnostic panel for depression is established, with a desirable AUC value of 0.933. Finally, proline levels are quantified in a follow-up cohort of depressive patients, highlighting the potential of metabolite quantification in the therapeutic evaluation of depression. This work promotes the progression of advanced matrixes and brings insights into the management of depression.

Association of preoperative frailty with the risk of postoperative delirium in older patients undergoing hip fracture surgery: a prospective cohort study.

OBJECTIVE: This study aimed to explore the correlation between preoperative frailty and the risk of postoperative delirium (POD) in older patients undergoing hip fracture surgery. METHODS: In total, 148 patients with hip fractures who were admitted to Tsinghua Changgung Hospital (Beijing, China) between January 2022 and January 2023 were involved in this study. Preoperative frailty scales were assessed, of which the CAM scale was postoperatively administered every morning and evening on days 1, 2, 3, 5, and 7. Binary logistic regression analysis was conducted to determine the correlation between preoperative frailty and the risk of POD. RESULTS: Among 148 older patients with hip fractures, 71 (48.0%) were identified as preoperative frail and 77 (52.0%) as non-frail. The overall incidence of POD on day 7 was 24.3% (36/148), and preoperative frailty was associated with a significantly higher risk of POD compared with non-frailty (42.3% vs. 7.8%, P < 0.001). The binary logistic regression analysis revealed that preoperative frailty was noted as an independent risk factor for the risk of POD in older patients undergoing hip fracture surgery (P = 0.002). CONCLUSION: Preoperative frailty increased the risk of POD in older patients undergoing hip fracture surgery. DISCUSSION: Preoperative assessment of frailty in geriatric hip surgery can timely identify potential risks and provide interventions targeting frailty factors to reduce the incidence of POD in older patients undergoing hip fracture surgery. The findings suggested that preoperative frailty could increase the risk of POD in older patients undergoing hip fracture surgery. Further research is necessary to determine whether perioperative interventions aimed at enhancing frailty can mitigate the risk of POD and improve prognosis in older patients undergoing hip fracture surgery.

Serum Metabolic Fingerprints Characterize Systemic Lupus Erythematosus.

Metabolic fingerprints in serum characterize diverse diseases for diagnostics and biomarker discovery. The identification of systemic lupus erythematosus (SLE) by serum metabolic fingerprints (SMFs) will facilitate precision medicine in SLE in an early and designed manner. Here, a discovery cohort of 731 individuals including 357 SLE patients and 374 healthy controls (HCs), and a validation cohort of 184 individuals (SLE/HC, 91/93) are constructed. Each SMF is directly recorded by nano-assisted laser desorption/ionization mass spectrometry (LDI MS) within 1 minute using 1 µL of native serum, which contains 908 mass to charge features. Sparse learning of SMFs achieves the SLE identification with sensitivity/specificity and area-under-the-curve (AUC) up to 86.0%/92.0% and 0.950 for the discovery cohort. For the independent validation cohort, it exhibits no performance loss by affording the sensitivity/specificity and AUC of 89.0%/100.0% and 0.992. Notably, a metabolic biomarker panel is screened out from the SMFs, demonstrating the unique metabolic pattern of SLE patients different from both HCs and rheumatoid arthritis patients. In conclusion, SMFs characterize SLE by revealing its unique metabolic pattern. Different regulation of small molecule metabolites contributes to the precise diagnosis of autoimmune disease and further exploration of the pathogenic mechanisms.

Antifungal compounds of Chinese prickly ash against drug-resistant Candida albicans.

The leaf of Chinese prickly ash, a unique spice having typical pungent sensation, is a popular food in Southwest China with antipruritic, insecticidal and fungicidal functions, but its bioactive constituents of fungistatic capacity remain unknown. In present investigation, twenty-nine compounds were isolated from leaf of Chinese prickly ash, and their antifungal bioactivity against drug-resistant Candida albicans were evaluated in vitro and in vivo. As a result, three compounds 3, 10, 29 showed antifungal bioactivity by damage of the fungal biofilm, and they might recover sensitive of drug resistant C. albicans to Fluconazole. Then Chinese prickly ash leaf was proved to be a functional food against fungus for the first time in experiment.

The Protective Effect of Sweet Potato Root Tuber on Chemotherapy-Induced Thrombocytopenia.

SCOPE: Sweet potato (Ipomoea batatas L.) is one of the leading crops worldwide, containing high nutritional components such as fiber and polyphenols. Root tuber of Simon 1 (SIMON), a cultivar of sweet potato, is a folk food in China with a hemostasis function but lacking experimental data support. METHODS AND RESULTS: Now the protective effect of SIMON on chemotherapy-induced thrombocytopenia (CIT), a serious complication of cancer treatment, is investigated for the first time by a CIT mouse model induced by intraperitoneal injection of carboplatin. As a result, SIMON raises the number of peripheral platelets, white blood cells, and bone marrow nucleated cells in CIT mice significantly. Besides, carboplatin-induced atrophy of the thymus, spleen, and disordered metabolism of the inflammatory immune system and glycerophospholipids are also reversed by SIMON. Phytochemical analysis of SIMON indicates 16 compounds including eight phenolic derivatives, which might be associated with its anti-CIT bioactivity. CONCLUSION: Sweet potato (SIMON) may be an efficient function food in the prevention of bleeding disorders.

Chemistry and bioactivities of natural steroidal alkaloids.

Steroidal alkaloids possess the basic steroidal skeleton with a nitrogen atom in rings or side chains incorporated as an integral part of the molecule. They have demonstrated a wide range of biological activities, and some of them have even been developed as therapeutic drugs, such as abiraterone acetate (Zytiga®), a blockbuster drug, which has been used for the treatment of prostate cancer. Structurally diverse natural steroidal alkaloids present a wide spectrum of biological activities, which are attractive for natural product chemistry and medicinal chemistry communities. This review comprehensively covers the structural classification, isolation and various biological activities of 697 natural steroidal alkaloids discovered from 1926 to October 2021, with 363 references being cited.

Durvalumab consolidation therapy in patients with stage III non-small cell lung cancer after concurrent chemoradiation: a China-based cost-effectiveness analysis.

OBJECTIVE: To evaluate the cost-effectiveness of durvalumab in post-chemoradiotherapy patients with unresectable stage III NSCLC from the Chinese healthcare system perspective. METHODS: The study developed a five-health state Markov model to evaluate the cost-effectiveness of durvalumab consolidation therapy in post-chemoradiotherapy patients based on the PACIFIC clinical trial. Sensitivity and scenario analyses were performed to evaluate the model uncertainty. RESULTS: Durvalumab consolidation therapy provided an additional 1.22 quality-adjusted life-years (QALYs), with an incremental cost of $24,397 compared to no consolidation therapy in unselected patients. Durvalumab consolidation therapy was cost-effective as it yielded an incremental cost-effectiveness ratio (ICER) of $20,000 per QALY gained at a willingness-to-pay (WTP) threshold of $31,494 per QALY. In the patient subgroup with PD-L1-expressing tumors (≥1%), durvalumab was associated with an ICER of $33,058/QALY, resulting in a slight skewing away from the given cost-effectiveness threshold. The sensitivity analysis showed that ICERs were most sensitive to the cost of durvalumab, the cost of pembrolizumab, and the body weight of patients, regardless of PD-L1 expression selection. CONCLUSION: Durvalumab consolidation therapy is likely to be cost-effective in China, which indicates that expensive immunotherapies can gain clinical benefits at a justifiable cost in developing countries as well.

Preparation and Corrosion Performance of PPy/Silane Film on AZ31 Magnesium Alloy via One-Step Cyclic Voltammetry.

PPy/silane composite film on a magnesium alloy surface was prepared by one-step cycle voltammetry. The mixed solution of methanol and water was used as the hydrolysis solvent of a γ-(2,3-glycidoxypropyl) trimethoxysilane coupling agent (KH-560). The surface morphology of the PPy/silane film, the electro-polymerization progress of KH-560 and PPy, the influence of the silane coupling agent and the corrosion behavior of the coated AZ31 Mg alloy were all investigated. The results indicated that the PPy/silane film on AZ31 Mg alloy via one-step cyclic voltammetry could provide better corrosion protection for an Mg alloy when the volume fraction of KH-560 in the hydrolysis solution was 15% and the time span of hydrolysis was 24 h with the 5.935 × 10-10 A cm-2 corrosion current density.

Bioguided isolation, identification and bioactivity evaluation of anti-MRSA constituents from Morus alba Linn.

ETHNOPHARMACOLOGY RELEVANCE: The root bark of Morus alba Linn. (M. alba), a traditional folk medicine, has been documented in the Chinese Pharmacopoeia, which has been widely used for asthma, fever, pneumonia, edema, vomit, colitis, bronchitis and keratitis diseases. Some of the diseases may be related to respiratory, digestive, urinary tract infections. Although Diels-Alder adducts (DAAs), flavonoids, 2-arylbenzofurans and stilbene compounds have been isolated from the root bark of M. alba, few compounds are reported for their antimicrobial efficacy in vivo and the mechanism. AIM OF THE STUDY: The aim of the study was to isolate and identify compounds of the root bark of M. alba in view of their anti-MRSA bioactivity, evaluate the anti-MRSA bioactivity of compounds and 60% ethanol elution (MA-6) in vitro and in vivo, and explore preliminary antibacterial mechanism in order to provide natural resources against MRSA infection. MATERIALS AND METHODS: Systematic phytochemical investigations were carried out according to the thin layer chromatography (TLC) of the active fraction MA-6 to find more anti-MRSA ingredients. The compounds of the root bark of M. alba were separated by column chromatography and identified by LC-MS/MS and NMR spectroscopy. The anti-MRSA efficacy of the active ingredients were evaluated by broth microdilution method and a murine infection model. The mode of action of compounds was explored by time-kill curve and post-contact effect. The preliminary mechanism of compounds against MRSA was explored by drug efflux pumps and bacterial biofilms. RESULTS: Chemical isolation resulted in twenty-nine known compounds, most with one or more geranyl and prenyl units exhibited superior anti-MRSA bioactivity, with MIC values of 2-16 µg/mL. In addition, the mode of action indicated that compounds presented persistent antimicrobial effect, which also produced concentration-dependent and time-dependent killing activity or property. Preliminary mechanism showed that the compound kuwanon O (29) damaged the bacterial cell membranes, leading to the accumulation of antibiotics inside bacterial cells, moreover, MA-6 and kuwanon O (29) inhibited the efflux of drugs by combining with methicillin or ethidium bromide (EtBr), resulting in the MICs of EtBr and methicillin were obviously decreased three-fold. The anti-MRSA efficacy in vivo indicated that the active fraction MA-6 could reduce bacteria in spleen, liver, kidney and mortality of acutely infectious mice, which was better than the positive drug berberine chloride. CONCLUSION: Experimental investigation showed that the MA-6 and compound 29 have promising bioactivity against MRSA in vitro and in vivo, which might be used as a potential source of new antibacterial medicine or a potential efflux pump inhibitor against MRSA infection.

Bioguided isolation, identification and activity evaluation of antifungal compounds from Acorus tatarinowii Schott.

ETHNOPHARMACOLOGY RELEVANCE: As a traditional folk medicine, Acorus tatarinowii Schott was used to treat digestive diseases, such as diarrhea, which may be related to Candida albicans infection; however according to literature surveys, there have been few studies of A. tatarinowii focusing on its antimicrobial activity, and almost all describe investigations using crude extracts or fractions. AIM OF THE STUDY: The aims of the current study were to isolate and identify antifungal fractions of A. tatarinowii based on their antifungal activity, explore the preliminary mechanism of 60% ethanol elution (AT60) by metabonomics, and evaluate the antifungal activity of AT60 in vivo and in vitro, to provide natural resources against fungal infections. MATERIALS AND METHODS: As a pilot evaluation of activity, A. tatarinowii fractions and compounds with antifungal bioactivity were isolated by bioactive-guided column chromatography, and identified by LC-QTOF-MS/MS and NMR spectroscopy. The antifungal effects of the active ingredients against resistant C. albicans were evaluated by in vivo and in vitro colony forming unit assays. The mechanism underlying the activity of AT60 against C. albicans was explored using an LC-QTOF-based metabonomics approach and fluorescence microscopy imaging. RESULTS: AT60 showed better activity against C. albicans than the same dose of the first line antifungal drugs, fluconazole and itraconazole (positive control drugs). Subsequent phytochemical investigation of AT60 identified twenty-five known compounds, six of which were isolated: asaraldehyde (7), 1-(2,4,5-trimethoxyphenyl)-1,2-propanediol (12), α-asarone (14), ß-asarone (15), γ-asarone (18), acotatarone C (19). Further, the compounds α-asarone (14) and acotatarone C (19) may be responsible for the antifungal activity, and exhibit synergistic effects. Metabonomics analysis indicated that AT60 can inhibit biofilm formation by regulating the C. albicans protein kinase C pathway. CONCLUSIONS: Our results show that A. tatarinowii has potent bioactivity against C. albicans in vitro and in vivo, and can be considered an antifungal botanic agent.

Comparative investigation of phytochemicals among ten citrus herbs by ultra high performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry and evaluation of their antioxidant properties.

The citrus herbs have proved their important medicinal and nutritional values as medicine-food dual-purpose herbs, functional foods, or medical herbs in China. In this study, phytochemicals and antioxidant activity among ten typical citrus herbs (ethanol extracts) were investigated comprehensively. The major ingredients and their contents were analyzed by high-resolution mass spectrometry, and the differences of typical fragment ions between flavanone-7-O-rutinoside(s) and flavanone-7-O-neohesperidoside(s) were discriminated properly in negative electrospray ionization mode. Total polyphenols, total flavonoids, 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), and ferric reducing antioxidant power tests were performed, which indicated their beneficial values and antioxidant effects. The medicine-food dual-purpose herbs including Chenpi, Juluo, Daidaihua, Huajuhong, Xiangyuan, and Foshou exhibited antioxidant capacities significantly by decreasing intracellular reactive oxygen species intensity (P < 0.01), enhancing superoxide dismutase, catalase, and glutathione peroxidase activities (P < 0.01) in H2 O2 -induced RIN-m5F cells. Moreover, the functional foods Zhishi, Zhiqiao, and Qingpi showed moderate antioxidant bioactivity, while the medical herb Juhe showed weak antioxidant bioactivity, which were consistent with the multivariate analysis of their major flavonoids. The study provided a new sight for the chemical differentiation and practical application of citrus herbs as medicine-food dual-purpose herbs, functional foods, or medical herbs.