Synthesis of the spiroimine fragment of portimines A and B.

Portimines A and B are spirocyclic imine natural products, which display remarkable anticancer, anti-HIV, and antifouling activities. Herein, we report a facile synthesis of the spirocyclic core of portimines A and B. Our strategy utilized a scalable Diels-Alder addition of a 2-bromo-1,3-butadiene to a symmetrical malonate dienophile, coupled with a diastereoselective lactonization of the resulting malonate that enabled differentiation of the two carbonyl groups. This approach overcame issues encountered in previous studies focused on the use of exo selective Diels-Alder reactions, by programming formation of the key stereodiad of the spiroimine fragment into the diastereoselective lactonization event, rather than the cycloaddition step. Elaboration of the key lactone intermediate afforded a functionalized spirolactam fragment as a useful intermediate en route to the portimines. Importantly, a key alcohol intermediate could be resolved by enzymatic resolution, thereby providing an asymmetric route to the spiroimine fragment of portimines A and B.

Polyphenol Profile, Antioxidant Activity, and Hypolipidemic Effect of Longan Byproducts.

Longan, a popular fruit in Asia, has been used in traditional Chinese medicine to treat several diseases for centuries. Recent studies have indicated that longan byproducts are rich in polyphenols. The aim of this study was to analyze the phenolic composition of longan byproduct polyphenol extracts (LPPE), evaluate their antioxidant activity in vitro, and investigate their regulating effect on lipid metabolism in vivo. The results indicated that the antioxidant activity of LPPE was 231.350 ± 21.640, 252.380 ± 31.150, and 558.220 ± 59.810 (mg Vc/g) as determined by DPPH, ABTS, and FRAP, respectively. UPLC-QqQ-MS/MS analysis indicated that the main compounds in LPPE were gallic acid, proanthocyanidin, epicatechin, and phlorizin. LPPE supplementation prevented the body weight gain and decreased serum and liver lipids in high-fat diet-induced-obese mice. Furthermore, RT-PCR and Western blot analysis indicated that LPPE upregulated the expression of PPARα and LXRα and then regulated their target genes, including FAS, CYP7A1, and CYP27A1, which are involved in lipid homeostasis. Taken together, this study supports the concept that LPPE can be used as a dietary supplement in regulating lipid metabolism.

1.9 µm all-optical wavelength converter based on a graphene oxide coated microfiber.

An all-optical wavelength converter based on graphene oxide (GO) is proposed at the 1.9 µm band. The homemade GO-coated microfiber is acquired through the optical deposition method, which shows a remarkable nonlinear optical response. Stable conversion efficiency up to -45.52 dB is obtained with 1 nm wavelength interval, and the wavelength tuning range can reach 6 nm (1969-1975 nm). With fixed wavelength interval, the conversion efficiency can increase with the increase of pump power. Simultaneously, the fluctuation of conversion efficiency is ±0.41 dB within 2 hours. The demonstrated all-optical wavelength converter based on GO can play an outstanding role in the future of all-optical communications and networks.

Triglyceride-glucose index and the incidence of atherosclerotic cardiovascular diseases: a meta-analysis of cohort studies.

BACKGROUND: Insulin resistance has been demonstrated to be involved in the pathogenesis of atherosclerotic cardiovascular diseases (ASCVDs). This study evaluated the association between the triglyceride-glucose (TyG) index, a novel surrogate indicator of insulin resistance, and the incidence of ASCVDs in people without ASCVDs at baseline by performing a meta-analysis. METHODS: Cohort studies reporting the multivariate-adjusted association between the TyG index and the incidence of ASCVDs were obtained by searching the PubMed and Embase databases. A random-effects model incorporating intra-study heterogeneity was applied to combine the results. RESULTS: Eight cohort studies comprising 5,731,294 participants were included in this meta-analysis. The results showed that compared to those with the lowest TyG index category, participants with the highest TyG index category were independently associated with a higher risk of ASCVDs [hazard ratio (HR): 1.61, 95% confidence interval (CI) 1.29-2.01, I2 = 80%, P < 0.001]. This finding was consistent with the meta-analysis results with the TyG index analyzed as a continuous variable (HR per 1-unit increment of the TyG index: 1.39, 95% CI 1.18-1.64, I2 = 89%, P < 0.001). Subgroup analyses suggested that the age, sex, and diabetic status did not significantly affect the association (for subgroup analyses, all P > 0.05). Moreover, participants with the highest TyG index category were independently associated with a higher risk of coronary artery disease [(CAD), HR: 1.95, 95% CI 1.47-2.58, I2 = 92%, P < 0.001] and stroke (HR: 1.26, 95% CI 1.23-1.29, I2 = 0%, P < 0.001). CONCLUSIONS: A higher TyG index may be independently associated with a higher incidence of ASCVDs, CAD, and stroke in people without ASCVDs at baseline.

Effect of spectral CT on tumor microvascular angiogenesis in renal cell carcinoma.

BACKGROUND: To examine the value of energetic-spectrum computed tomography (spectral CT) quantitative parameters in renal cell carcinoma (RCC) microvascular angiogenesis. METHODS: The authors evaluated 32 patients with pathologically confirmed RCC who underwent triple-phase contrast-enhanced CT with spectral CT imaging mode from January 2017 to December 2019. Quantitative parameters include parameters derived from iodine concentration (IC) and water concentration (WC) of 120 keV monochromatic images. All specimens were evaluated including the microvascular density (MVD), microvascular area (MVA) and so on. The correlation between IC and WC (including average values and random values) with microvascular parameters were analyzed with Pearson or Spearman rank correlation coefficients. RESULTS: The MVD of all tumors was 26.00 (15.00-43.75) vessels per field at × 400 magnification. The MVD of RCC correlated positively with the mean IC, mean WC, mean NWC, mean NIC, random IC, random NIC in renal cortical phase, WCD1, WCD2, NWCD2 and ICD1 (Spearman rank correlation coefficients, r range, 0.362-0.533; all p < 0.05). The MVA of all tumors was (16.16 ± 8.98) % per field at × 400 magnification. The MVA of RCC correlated positively with the mean IC, mean WC, mean NWC, mean NIC, random IC, random NIC in renal cortical, mean WC and mean NWC in renal parenchymal phase, WCD1, WCD2, WCD3, NWCD2, and NWCD3 (Pearson or Spearman rank correlation coefficients, r range, 0.357-0.576; all p < 0.05). Microvascular grading correlated positively with the mean NWC, mean NIC and random NIC in renal cortical phase, mean NWC in renal parenchymal phase, NWCD2, WCD3, NWCD3, NICD2 and NICD3 (Spearman rank correlation coefficients, r range, 0.367-0.520; all p < 0.05). As for tumor diameter (55.19 ± 19.15), µm, only NWCD3 was associated with it (Spearman rank correlation coefficients, r = 0.388; p < 0.05). CONCLUSIONS: ICD and WCD of spectral CT have a potential for evaluating RCC microvascular angiogenesis. MVD, MVA and microvascular grade showed moderate positive correlation with ICD and WCD. ICD displayed more relevant than that of WCD. The parameters of renal cortical phase were the best in three phases. NICD and NWCD manifested stronger correlation with microvascular parameters than that of ICD and WCD.

Long-term inter-platform reproducibility, bias, and linearity of commercial PDFF MRI methods for fat quantification: a multi-center, multi-vendor phantom study.

OBJECTIVES: Proton density fat fraction (PDFF) is a validated biomarker of tissue fat quantification. However, validation has been limited to single-center or multi-center series using non-FDA-approved software. Thus, we assess the bias, linearity, and long-term reproducibility of PDFF obtained using commercial PDFF packages from several vendors. METHODS: Over 35 months, 438 subjects and 16 volunteers from a multi-center observational trial underwent PDFF MRI measurements using a 3-T MR system from one of three different vendors or a 1.5-T system from one vendor. Fat-water phantom sets were measured as part of each subject's examination. Manual region-of-interest measurements on the %fat image, then cross-sectional bias, linearity, and long-term reproducibility were assessed. RESULTS: Three hundred ninety-two phantom measurements were evaluable (90%). Bias ranged from 2.4 to - 3.8% for the lowest to the highest weight %fat. Regression fits of PDFF against synthesis weight %fat showed negligible non-linear effects and a linear slope of 0.94 (95% confidence interval: 0.938, 0.947). We observed significant vendor (p < 0.001) and field strength (p < 0.001) differences in bias and longitudinal variability. When the results were pooled across sites, vendors, and field strengths, the estimated reproducibility coefficient was 6.93% (95% CI: 6.25%, 7.81%). CONCLUSIONS: This study demonstrated good linearity, accuracy, and reproducibility for all investigated manufacturers and field strengths. However, significant vendor-dependent and field strength-dependent bias were found. While longitudinal PDFF measurements may be made using different field strength or vendor MR systems, if the MR system is not the same, based on these results, only PDFF changes ≥ 7% can be considered a true difference. KEY POINTS: • Phantom fat fraction (PDFF) MRI measurements over 35 months demonstrated good linearity, accuracy, and reproducibility for the vendor systems investigated. • Non-linear effects were negligible (linear slope of 0.94) over 0-100% fat; however, significant vendor (p < 0.001) and field strength (p<0.001) differences in bias and longitudinal variability were identified. Bias ranged from 2.4 to - 3.8% for 0-100 weight% fat, respectively. • Measurement bias could affect the accuracy of PDFF in clinical use. As the reproducibility coefficient was 6.93%, only greater changes in % fat can be considered true differences when making longitudinal PDFF measurements on different MR systems.

Synthesis of the C4-C16 Polyketide Fragment of Portimines A and B.

Stereoselective synthesis of the C4-C16 polyketide fragment of portimines A and B is reported, enabled by our previously established method for the stereoselective synthesis of syn-α,α'-dihydroxyketones. The preparation of this advanced fragment provides insights useful for the total synthesis of portimines A and B. An asymmetric Evans aldol reaction was used to install the C10-C11 adjacent stereogenic centers before incorporation of indantrione, followed by epoxidation and epoxide opening to forge the challenging syn-α,α'-dihydroxyketone functionality.

3-dimensional ultrasound-guided percutaneous nephrolithotomy: total free versus partial fluoroscopy.

PURPOSE: To provide a comprehensive analysis about safety and efficacy of fluoroscopy-free total ultrasound-guided percutaneous nephrolithotomy (TUPN) versus ultrasound with fluoroscopy-guided percutaneous nephrolithotomy (UFPN). PATIENTS AND METHODS: 3-dimensional ultrasound-guided PCNL was retrospectively analyzed in 377 patients from 2015 to 2017. TUPN was performed in 185 patients and UFPN was finished in 192 patients. In TUPN group, the entire procedures of puncture and dilation were real-time monitored by three-dimensional ultrasound alone. Conversely, in UFPN group, the puncture was performed under the guidance of real-time ultrasound, while the dilation was monitored by fluoroscopy. Preoperative demographic data, intraoperative parameters and postoperative complications were compared. RESULTS: Groups were comparable in baseline characteristics. Fifty percent of patients were Guy's score III-IV and over half of the patients were mild or none of hydronephrosis. All renal punctures were successfully performed. The primary successful rates of dilation were more than 95% in both groups (95.1% in TUPN and 95.8% in UFPN, p = 0.74). Two or more accesses were established in 33 patients (17.8%) in TUPN group and 25 patients (13%) in UFPN group (p = 0.20). Post-operative instant stone-free rates were 88.6% and 90.1%, TUPN versus UFPN, respectively, p = 0.65. Most of the complications were minor and there were no differences in Clavien-Dindo complications in both groups. Mean operating time and hospitalization were comparable. CONCLUSIONS: Our findings show that fluoroscopy-free total ultrasound-guided PCNL represents an alternatively safe and efficient approach for the treatment of renal stones. Further study will be required to evaluate fluoroscopy-free TUPN in various clinical settings.

Atypical focal xanthogranulomatous pyelonephritis without clinical symptoms presenting as infiltrative renal cancer: a case report and literature review.

BACKGROUND: Xanthogranulomatous pyelonephritis (XGP) is an uncommon form of chronic pyelonephritis. Most patients of XGP are diffuse in radiology and the clinical features are typical. CASE PRESENTATION: We present a case of 24-year-old female with the absence of symptoms and normal laboratory examinations. Contrast computed tomography and intravenous pyelography demonstrate infiltrative renal mass and renal cell carcinoma is presumed. Laparoscopic right radical nephrectomy is performed, but the final pathological result shows XGP. CONCLUSIONS: As far as we know, this is the first case report of XGP without any symptoms/signs and with normal laboratory examinations. The diagnosis of atypical XGP is challenging and preoperative renal mass biopsy should be considered in special cases.

Left lung cancer in a patient with congenital unilateral absence of the left pulmonary artery: a case report and literature review.

BACKGROUND: Unilateral absence of pulmonary artery (UAPA) is a rare congenital disease of pulmonary circulation, which is often accompanied by other cardiovascular anomalies. Infrequently, it may remain undiagnosed until adulthood. More rarely, it is to be found with lung cancer in the ipsilateral or contralateral lung simultaneously. CASE PRESENTATION: A 56-year-old man with complaints of intermittent left chest pain for 2 months was referred to our hospital. Chest computed tomography(CT) revealed a cavitary lesion measuring 5.5 cm × 5.7 cm in the superior segment of the left lower lobe. Absence of left pulmonary artery and right-sided aortic arch were found on chest computed tomography angiography (CTA). The tumor was successfully removed via left pneumonectomy, and postoperative histopathology showed that the tumor was a squamous cell carcinoma (T2bN1). At a postoperative 24-month follow-up, the patient was free of disease and no evidence of recurrence or metastasis. Based on literature review, this is the ninth case of lung cancer in UAPA patients. CONCLUSIONS: Lung cancer and UAPA occurred ipsilaterally in 66.7% of these cases (6/9), including the present case. For those patients who occurred contralaterally, surgical treatment may be more challenging. CT and CTA could provide an accurate diagnosis for this disease entity. Identification and recognition of this rare and special disease entity may facilitate timely diagnosis and appropriate treatment.

Highly Diastereoselective Synthesis of Syn-1,3-Dihydroxyketone Motifs from Propargylic Alcohols via Spiroepoxide Intermediates.

Syn dihydroxyketone motifs are embedded in a wide range of biologically active natural products, however the development of stereoselective synthetic methods to assemble these structures has proven a challenging task. We report a highly diastereoselective method for the synthesis of syn dihydroxyketones from propargylic alcohols, with wide scope for application in natural product synthesis. The reaction sequence involves regioselective cyclisation of propargylic alcohols with incorporation of a triketone to give enol dioxolanes that are then diastereoselectively epoxidised to form unusual spiroepoxide intermediates. Hydrolysis affords syn dihydroxyketones as essentially single diastereisomers. The reaction sequence is operationally simple, of wide substrate scope, and remarkably can be efficiently carried out as a one-pot process with no loss of overall yield or diastereoselectivity.

Reactivity of 2-Nitropyrrole Systems: Development of Improved Synthetic Approaches to Nitropyrrole Natural Products.

Fundamental study of the reactivity of 2-nitropyrrole systems has enabled the identification of effective methods for incorporation of this unusual motif into advanced natural product frameworks. The presence of electron-rich pyrrole N-protecting groups (BOM, Boz) was demonstrated to enable a variety of previously unsuccessful palladium-mediated cross-couplings to be carried out in high yield. Based on this foundation, a series of regio- and stereoselective synthetic routes toward the nitropyrrolin and heronapyrrole families of natural products was developed by our group (G1-3). A full account of the strategic evolution of these approaches is reported here, highlighting the details of the setbacks encountered and eventual successes achieved en route, including the total synthesis of heronapyrrole B. The fundamental studies and completed total syntheses provide general access to the bioactive 2-nitropyrrole natural product manifold and also establish practical and efficient methods for preparation and elaboration of the medicinally relevant 2-nitropyrrole motif.

Synthesis and biological evaluation of novel teixobactin analogues.

The cyclic depsipeptide, teixobactin, possesses promising activity against a range of antimicrobial-resistant (AMR) pathogenic bacteria, including Staphylococcus aureus and Mycobacterium tuberculosis. Teixobactin contains a number of non-canonical residues, including the synthetically challenging amino acid, l-allo-enduracididine, complicating clinical application of this peptide. Herein, we report the synthesis of six analogues of teixobactin, in which the non-canonical l-allo-enduracididine amino acid is replaced by isosteric, commercially available Fmoc-amino acid building blocks. Biological evaluation of the analogues has revealed promising activity, particularly for guanidine isosteres, against AMR strains of S. aureus and Enterococcus faecalis, highlighting the potential for this class of cyclic depsipeptides in the treatment of Gram-positive infections.

Nitropyrrole natural products: isolation, biosynthesis and total synthesis.

Nitropyrrole-containing natural products are relatively rare in nature. Known examples are limited to the ß-nitropyrrole-containing pyrrolomycins and α-nitropyrrole-containing nitropyrrolins and heronapyrroles. Their unique structures and interesting bioactivity are of ongoing interest to the chemistry community. This review describes the isolation, biological activity, biosynthesis and chemical synthesis of nitropyrrole-containing natural products reported to date.

[Applications of Instant Biochemical Detector in Pediatrics Based on POCT Mode].

Based on the analysis of many problems in the process of pediatric biochemical testing, this paper summarizes the technical basis and advantages of POCT (point-of-care testing) mode, and introduces several applications of instant biochemical detector in pediatrics on POCT mode. The prospects of the POCT mode are discussed at the end.

Lipase member H is a novel secreted protein associated with a poor prognosis for breast cancer patients.

The objective of this study is to identify the expression status and clinical implications of lipase member H (LIPH) in breast cancer in order to develop strategies for breast cancer management. LIPH expression status was detected in 346 breast cancer specimens by immunohistochemistry. The relationship between LIPH expression, clinico-pathological parameters, and prognosis of breast cancer was determined. LIPH expression was higher in breast cancer specimens than in paracarcinoma tissues (P=0.01). In total, 64.74% (224/346) of breast cancer samples had high expression of the LIPH protein. LIPH was related to tumor size, histological grade, lymph node metastasis, and distant metastasis (P=0.073, 0.001, 0.001, and 0.001, respectively). Furthermore, individuals with high LIPH expression had a significantly higher rate of distant metastasis and poorer disease-specific survival than those with no or low LIPH expression (P=0.01). A Cox regression test indicated that the LIPH protein was an independent prognostic factor (P=0.001). LIPH was differentially expressed in breast cancer individuals and is an independent prognostic factor for breast cancer as well as a potential target for its management.

Fast-charging anodes for lithium ion batteries: progress and challenges.

Slow charging speed has been a serious constraint to the promotion of electric vehicles (EVs), and therefore the development of advanced lithium-ion batteries (LIBs) with fast-charging capability has become an urgent task. Thanks to its low price and excellent overall electrochemical performance, graphite has dominated the anode market for the past 30 years. However, it is difficult to meet the development needs of fast-charging batteries using graphite anodes due to their fast capacity degradation and safety hazards under high-current charging processes. This feature article describes the failure mechanism of graphite anodes under fast charging, and then summarizes the basic principles, current research progress, advanced strategies and challenges of fast-charging anodes represented by graphite, lithium titanate (Li4Ti5O12) and niobium-based oxides. Moreover, we look forward to the development prospects of fast-charging anodes and provide some guidance for future research in the field of fast-charging batteries.

The role of the SIRT1-BMAL1 pathway in regulating oxidative stress in the early development of ischaemic stroke.

Oxidative stress is the primary cause of ischaemic stroke and is closely related to circadian rhythm. However, the mechanism by which circadian rhythm regulates oxidative stress in ischaemic stroke remains elusive. The Silent Information Regulator 1 (SIRT1) controls circadian rhythm by activating the transcription of the circadian clock core protein Basic Helix-Loop-Helix ARNT Like 1 (BMAL1) through deacetylation. Studies have shown that the SIRT1-BMAL1 pathway can regulate oxidative stress. To investigate its correlation with oxidative stress, we examined the expression levels and influencing factors of SIRT1-BMAL1 at different times in ischaemic stroke patients and analyzed their clinical indexes, oxidative stress, and inflammatory factor indicators. The expression levels of oxidative stress and inflammatory factor indicators, including malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-6 (IL-6), and tumor necrosis factor-a (TNF-α), SIRT1, and BMAL1, were detected in ischaemic stroke patients within 4.5 h of onset and in non-stroke patients. Patients were divided into four subgroups based on onset time: subgroup 1 (0:00-05:59); subgroup 2 (06:00-11:59); subgroup 3 (12:00-17: 59); and subgroup 4 (18:00-23:59). Our results showed higher MDA, IL-6, and TNF-α levels, and lower SOD, SIRT1, and BMAL1 levels in ischaemic stroke patients compared to control patients (P < 0.05). Among the four subgroups, the content of MDA, IL-6, and TNF-α was highest in patients with ischaemic stroke onset from subgroup 2 (06:00-11:59), while the expression levels of SOD, BMAL1, and SIRT1 were lowest in patients with ischaemic stroke in subgroup 2. Additionally, myeloperoxidase (MPO) reached the highest value showing the same trends consistent with MDA, IL-6, and TNF-ɑ and opposite trends consistent with SOD, BMAL1, and SIRT1. However, triglycerides (TGs), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), immediate blood glucose, immediate diastolic blood pressure, immediate systolic blood pressure, and homocysteine (HCY) did not show any statistically significant circadian rhythm changes (P > 0.05). Our findings suggest that the SIRT1-BMAL1 pathway may be involved in early oxidative stress in ischaemic stroke, which may be related to MPO.

Continuation of immunotherapy beyond progression is beneficial to the survival of advanced non-small-cell lung cancer.

PURPOSE: To investigate the potential clinical importance of continuing immunotherapy beyond progression in patients with advanced non-small-cell lung cancer (aNSCLC). METHODS: The data of patients with aNSCLC who experienced progressive disease after receiving first-line immunotherapy plus chemotherapy were collected from multiple centers for the period from January 1, 2018 to May 31, 2022. According to the second-line treatment, the patients were classified into two groups: the continuation of immunotherapy beyond progression (CIBP) group and the discontinuation of immunotherapy beyond progression (DIBP) group. The efficacy and safety of the treatment were compared between the groups. RESULTS: Overall, data from 169 patients were analyzed; 93 patients were enrolled in the CIBP group and 76 patients were in the DIBP group. The median second-line progression-free survival was 5.5 months in the CIBP group, which for the DIBP group was 3.4 (p = 0.011). The median overall survival of the CIBP group was 13.3 months, whereas that of the DIBP group was 8.8 months (p = 0.031). The disease control rate of the CIBP group (79.57%) was observably higher than that of the DIBP group (64.47%; p = 0.028). Among patients who responded better (complete or partial response) to prior therapy, the median progression-free survival was 5.5 months and 3.3 months in the CIBP and DIBP groups respectively (p = 0.022), and the median overall survival was 14.8 months and 8.8 months in the CIBP and DIBP groups respectively (p = 0.046). CONCLUSIONS: Continuing immunotherapy as a second-line treatment could be beneficial to the survival of patients with aNSCLC with disease progression beyond initial chemotherapy combined with immunotherapy.

Mesoscale size-promoted targeted therapy for acute kidney injury through combined RONS scavenging and inflammation alleviation strategy.

Acute kidney injury (AKI) is a heterogeneous, high-mortality clinical syndrome with diverse pathogenesis and prognosis, but it lacks the effective therapy clinically. Its pathogenesis is associated with production of reactive oxygen/nitrogen species and infiltration of inflammatory cells. To overcome these pathogenic factors and improve the therapeutic efficiency, we synthesized triptolide-loaded mesoscale polydopamine melanin-mimetic nanoparticles (MeNP4TP) as the antioxidant plus anti-inflammatory therapeutic platform to synergistically scavenge reactive oxygen/nitrogen species (RONS), inhibit the activity of macrophages and dendritic cells, and generate Treg cells for AKI therapy. It was demonstrated that mesoscale size was beneficial for MeNP4TP to specifically accumulate at renal tubule cells, and MeNP4TP could significantly attenuate oxidative stress, reduce proinflammatory immune cells in renal, and repair renal function in cisplatin-induced AKI mouse model. MeNP4TP might be a potential candidate to inhibit oxidative damages and inflammatory events in AKI.