Nanoassembly of spider silk protein mediated by intrinsically disordered regions.

Spider silk is the self-assembling product of silk proteins each containing multiple repeating units. Each repeating unit is entirely intrinsically disordered or contains a small disordered domain. The role of the disordered domain/unit in conferring silk protein storage and self-assembly is not fully understood yet. Here, we used biophysical and biochemical techniques to investigate the self-assembly of a miniature version of a minor ampullate spidroin (denoted as miniMiSp). miniMiSp consists of two identical intrinsically disordered domains, one folded repetitive domain, and two folded terminal domains. Our data indicated that miniMiSp self-assembles into oligomers and further into liquid droplets. The oligomerization is attributed to the aggregation-prone property of both the disordered domains and the folded repetitive domain. Our results support the model of micellar structure for silk proteins at high protein concentrations. The disordered domain is indispensable for liquid droplet formation via liquid-liquid phase separation, and tyrosine residues located in the disordered domain make dominant contributions to stability of the liquid droplets. As the same tyrosine residues are also critical to fibrillation, the liquid droplets are likely an intermediate state between the solution state and the fiber state. Additionally, the terminal domains contribute to the pH- and salt-dependent self-assembly properties.

TFA-Promoted Cascade Sulfonylation/Rearrangement/Cyclization of 1,5-Diynols and Sodium Sulfinates to Construct Sulfonylated Benzo[b]fluorenes.

A novel conversion of 1,5-diynols into sulfonylated benzo[b]fluorenes is reported by a TFA-promoted cascade cyclization with sodium sulfinates under mild conditions. This strategy provides an efficient and practical approach for accessing various sulfonated benzo[b]fluorenes in moderate to excellent yields under metal-free conditions. On the basis of the control experimental results and density functional theory calculations, a possible cascade transformation mechanism consisting of the dehydration of propargylic alcohols, sulfonylation, allenylation, and Schmittel-type cyclization is proposed. It is worth noting that TFA played an important role in this cascade cyclization, which promoted C-SO2R bond cleavage in a propargylic sulfone intermediate to form allenyl sulfones, followed by Schmittel-type cyclization to give the target product.

Optimal assessment of the glomerular filtration rate in older chinese patients using the equations of the Berlin Initiative Study.

AIM: To evaluate the performances of the various estimated glomerular filtration rate (eGFR) equations of the Chronic Kidney Disease Epidemiology Collaboration, the Berlin Initiative Study (BIS), and the Full Age Spectrum (FAS) in older Chinese. METHODS: This study enrolled Chinese adults aged ≥ 65 years who underwent GFR measurements (via 99Tcm-DTPA renal dynamic imaging) in our hospital from 2011 to 2022. Using the measured glomerular filtration rate (mGFR) as the reference, we derived the bias, precision, accuracy, and consistency of each equation. RESULTS: We enrolled 519 participants, comprising 155 with mGFR ≥ 60 mL/min/1.73 m2 and 364 with mGFR < 60 mL/min/1.73 m2. In the total patients, the BIS equation based on creatinine and cystatin C (BIScr-cys) exhibited the lowest bias [median (95% confidence interval): 1.61 (0.77-2.18)], highest precision [interquartile range 11.82 (10.32-13.70)], highest accuracy (P30: 81.12%), and best consistency (95% limit of agreement: 101.5 mL/min/1.73 m2). In the mGFR ≥ 60 mL/min/1.73 m2 subgroup, the BIScr-cys and FAS equation based on creatinine and cystatin C (FAScr-cys) performed better than the other equations; in the mGFR < 60 mL/min/1.73 m2 subgroup, all equations exhibited relatively large deviations from the mGFR. Of all eight equations, the BIScr-cys performed the best. CONCLUSIONS: Although no equation was fully accurate in the mGFR < 60 mL/min/1.73 m2 subgroup, the BIScr-cys (of the eight equations) assessed the eGFRs of the entire population best. A new equation is urgently required for older Chinese and even East Asians, especially those with moderate-to-severe renal insufficiency.

A bioactive composite hydrogel dressing that promotes healing of both acute and chronic diabetic skin wounds.

Mesenchymal stem cell derived exosomes (MSC-Exos) demonstrate beneficial effects on wound healing via anti-inflammatory and angiogenic properties. Chitosan (CS) exhibits excellent biocompatibility and accelerates cellular migration, adhesion, and proliferation. The ions released from bioactive glass (BG) and titanium dioxide (TiO2) nanoparticles exhibit sustained angiogenic and antibacterial potency. In this study, CMCS-CEBT hydrogel was synthesized from exosomes encapsulated carboxymethyl chitosan (CMCS), chitosan nanoparticles (CS-NPs), BG, and TiO2 nanoparticles for a preliminary evaluation of its impacts on the treatment of full-thickness skin defects, diabetic wounds, and burn skin injury due to burns. In vitro analysis indicated that the hydrogel exhibits excellent cell compatibility, stimulates endothelial cell adhesion and proliferation, and presents anti-inflammatory, angiogenic, and antibacterial activities. In vivo, the composite hydrogel dressing accelerated a wound healing acceleration effect, stimulated angiogenesis, and increased collagen deposition and the expression of anti-inflammatory factors. This innovative composite hydrogel dressing as a potential clinical therapy, utilizing bioactive materials, holds promise as a potential clinical therapy that aims to facilitate the regeneration of acute and chronically damaged skin tissue.

Effects of finerenone and glucagon-like peptide 1 receptor agonists on cardiovascular and renal outcomes in type 2 diabetes mellitus: a systematic review and meta-analysis.

OBJECTIVE: To assess the effects of finerenone and glucagon-like peptide 1 receptor agonists (GLP1-RA) on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus (T2DM), and the relative cardiovascular benefits in patients with or without established atherosclerotic cardiovascular disease for different outcomes with these classes of drugs. METHODS: We searched PubMed, the Cochrane Library, and Embase from January 1, 2000, to December 30, 2022, to identify randomized controlled trials. The primary outcomes were the composite of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death (MACE); hospitalization for heart failure (HHF); and a composite of renal outcomes. The results were reported as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: In total, we identified 11 trials and 73,927 participants, 13,847 (18.7%) in finerenone trials and 60,080 (81.3%) in GLP1-RA trials. Finerenone reduced the risk of MACE by 13% (HR, 0.87; 95% CI, 0.79-0.95; P = 0.003), while GLP1-RA reduced the risk in a similar magnitude by 13% (HR, 0.87; 95% CI, 0.83-0.92; P < 0.001). For both drug classes, the effect on lowering the risk of MACE was restricted to approximately 14% in patients with established atherosclerotic cardiovascular disease (HR, 0.86; 95% CI, 0.82-0.90; P < 0.001), whereas no effect was observed in patients without established atherosclerotic cardiovascular disease (HR, 0.93; 95% CI, 0.85-1.02; P = 0.12). GLP1-RA reduced myocardial infarction, stroke and cardiovascular death more than finerenone (which appeared to have no effect). Only finerenone was beneficial for reducing the risk of HHF (HR, 0.78; 95% CI, 0.66-0.92; P = 0.003). Both finerenone (HR, 0.84; 95% CI, 0.77-0.92; P < 0.001) and GLP1-RA (HR, 0.81; 95% CI, 0.76-0.86; P < 0.001) reduced the risk of kidney disease progression, including macroalbuminuria, and finerenone was superior to GLP1-RA in delaying deterioration of kidney function. CONCLUSIONS: Finerenone and GLP1-RA lead to a risk reduction in MACE to a similar degree in patients with established atherosclerotic cardiovascular disease. For both drug classes, the effect on lowering the risk of progression of kidney disease was also in a similar magnitude in patients with T2DM, whereas only finerenone had a significant protective effect against HHF. Treatment decisions for patients with T2DM should consider the clinical benefit profiles of each drug.

Worldwide burden and trends of diabetes among people aged 70 years and older, 1990-2019: A systematic analysis for the Global Burden of Disease Study 2019.

BACKGROUND: Diabetes places a significant burden on personal and public health. However, a comprehensive assessment of the burden of diabetes in older adults is lacking. We aimed to estimate the global burden of diabetes and explore trends for the population aged ≥70 from 1990 to 2019. METHODS: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, the prevalence, mortality, and disability-adjusted life-years (DALYs) of diabetes among people aged ≥70 were estimated by sex and age group in 2019. We also assessed the epidemiological trend of diabetes from 1990 to 2019. RESULTS: In 2019, 110.1 million (95% uncertainty interval [UI]: 101.2-119.4) people aged ≥70 years were living with diabetes (types 1 and 2 combined) with a global prevalence of 23.7% (21.8%-25.8%). Worldwide, 181.9 deaths (163.0-194.7) per 100,000 population and 4512.3 DALYs (3861.3-5264.2) per 100,000 population occurred due to diabetes. In 2019, minor sex-related disparities in the burden of diabetes were identified among specific age and sex groups. From 1990 to 2019, the prevalence of diabetes increased by 39.7% (37.7%-41.7%), and the related mortality and DALY rates also increased (16.4% [9.43%-22.9%] and 22.3% [17.2%-27.0%], respectively). CONCLUSION AND RELEVANCE: The global burden of diabetes in adults aged ≥70 has increased markedly from 1990 to 2019. As the population continues to age, there is an urgent need to combat the increasing disease burden.

Prevalence and risk factors associated with gastrointestinal parasites in goats (Capra hircus) and sheep (Ovis aries) from three provinces of China.

Gastrointestinal (GI) parasites in small ruminants, especially goats and sheep, have caused significant socio-economic and public health challenges worldwide. The aim of the present study was to investigate the diversity and prevalence of GI parasites in goats and sheep in Jiangsu, Shaanxi and Hunan provinces of China, and to assess whether the age of animals, sampling season and feeding mode influence the distribution and infection of GI parasites. A total of 1,081 fecal samples collected from goats (n = 835) and sheep (n = 246) were detected by saturated saline flotation technique and nylon sifter elutriation and sieving method for eggs/oocysts, respectively. Based on the morphological observation of eggs and oocysts, one tapeworm, five nematodes, three trematodes and nineteen coccidia were identified, of which seven helminths belong to zoonotic parasites. The infection rate of parasites was 83.4% (902/1081) in total samples, 91.6% (765/835) in goats, and 55.7% (137/246) in sheep. The infection rate of coccidia was 71.0% (767/1081), and that of helminths was 56.2% (607/1081). The dominant species was E. alijeri (67.3%, 562/835) in goats, E. parva (30.1%, 74/246) in sheep. The highest prevalent helminths were Trichostrongylidae spp. in goats (58.3%, 487/835), and Moniezia spp. in sheep (22.76%, 56/246). Of 902 positive samples, 825 (91.5%, 825/902) contained multiple (2-10) parasites. The feeding mode, sampling season and regions were relevant risk factors which have significant influence on the occurrence of GI parasites in goats and sheep. The risk coefficient of parasite infection in autumn was 2.49 times higher than spring (Odds ratio = 2.49, 95% CI = 1.51-4.09, p < 0.001). Compared to raising on the high beds, the goats and sheep raising on the ground had the higher risk of parasite infection (OR = 3.91, 95% CI = 2.07-7.40, p < 0.001). The risk coefficient of parasite infection in Shaanxi and Hunan was 3.78 and 1.25 times higher than that in Jiangsu (OR = 3.78, 95% CI = 2.01-7.12, p < 0.001; OR = 1.25, 95% CI = 1.21-1.29, p < 0.001). These data are significant for the development of prevention strategies to minimise economic losses from small ruminant production and to reduce the risk of water and food infecting humans as vectors of zoonotic parasitic diseases.

Serum PLA2R antibody as a predictive biomarker for venous thromboembolism risk in primary membranous nephropathy / El anticuerpo PLA2R sérico como biomarcador predictivo del riesgo de tromboembolia venosa en la nefropatía membranosa primaria

Background Patients with nephrotic syndrome are at high risk of venous thromboembolism (VTE), especially for primary membranous nephropathy (PMN). The phospholipase A2 receptor (PLA2R) is a marker of primary membranous nephropathy activity. This study investigated the predictive value of PLA2R antibodies in PMN for VTE.Methods In this retrospective study, we included 97 PMN patients and evaluated the predictive value of serum PLA2R antibodies for VTE risk. Lower extremity venous ultrasound, renal vein ultrasound, or spiral computed tomography pulmonary arteriography were used to assess VTE events. Serum anti-PLA2R antibodies were detected by enzyme-linked immunosorbent assay (ELISA). The risk of VTE was stratified according to serum albumin levels. Results Twenty PMN patients (21%) had thromboembolic events. Eight (15%) of patients with serum albumin >25g/l developed VTE, 6 of whom were positive for serum PLA2R antibodies. Positive serum PLA2R antibodies were significantly associated with VTE events in patients with serum albumin >25g/l (p=0.01). Age, sex, blood creatinine, serum albumin, and 24-h urine protein levels were not statistically different between the two groups. Kaplan–Meier analysis using the log-rank test revealed anti-PLA2R positive membranous nephropathy patients had more probability of VTE events than anti-PLA2R negative patients. Univariate Cox proportional hazards analysis revealed that lnPLA2R-Ab is an unfavorable predictor for VTE events in patients with serum albumin >25g/l (hazard ratio (HR) 2.1, p=0.01). Conclusions The PLA2R antibody was a risk predictor for thromboembolic events in patients with primary membranous nephropathy with serum albumin >25g/l (AU)

Antecedentes Los pacientes con síndrome nefrótico presentan un alto riesgo de tromboembolia venosa (TEV), especialmente en el caso de la nefropatía membranosa primaria (NMP). El receptor de fosfolipasa A2 (PLA2R) es un marcador de la actividad de la NMP. Este estudio investigó el valor predictivo de los anticuerpos PLA2R en NMP para TEV. Métodos En este estudio retrospectivo, se incluyeron 97 pacientes con NMP y se evaluó el valor predictivo de los anticuerpos PLA2R en suero para el riesgo de TEV. Se utilizaron la ecografía venosa de las extremidades inferiores, la ecografía de la vena renal o la arteriografía pulmonar por tomografía computarizada en espiral para evaluar los episodios de TEV. Los anticuerpos séricos anti-PLA2R se detectaron mediante un ensayo inmunoenzimático (ELISA). El riesgo de TEV se estratificó en función de los niveles de albúmina sérica. Resultados Veinte pacientes con NMP (21%) presentaron episodios tromboembólicos. Ocho (15%) de los pacientes con albúmina sérica>25g/l desarrollaron TEV, 6 de los cuales fueron positivos para anticuerpos PLA2R séricos. La positividad de los anticuerpos PLA2R séricos se asoció significativamente con episodios de TEV en pacientes con albúmina sérica>25g/l (p=0,01). La edad, el sexo, la creatinina en sangre, la albúmina sérica y los niveles de proteínas en orina de 24h no fueron estadísticamente diferentes entre los 2 grupos. El análisis de Kaplan-Meier mediante la prueba de rangos logarítmicos reveló que los pacientes con nefropatía membranosa positivos para anti-PLA2R tenían más probabilidad de sufrir TEV que los pacientes negativos para anti-PLA2R. El análisis univariante de riesgos proporcionales de Cox reveló que ln PLA2R-Ab es un predictor desfavorable de episodios de TEV en pacientes con albúmina sérica>25g/l (hazard ratio 2,1; p=0,01). Conclusiones El anticuerpo PLA2R fue un predictor de riesgo de episodios tromboembólicos en pacientes con NMP con albúmina sérica>25g/l (AU)

Cascade Cyclization of 1,5-Diynols and (RO)2P(O)SH to Construct Benzo[b]fluorenyl S-Alkyl Phosphorothioates under Catalyst-Free Conditions.

An efficient and practical cascade cyclization of 1,5-diynols with (RO)2P(O)SH as the acid promoter and nucleophile under mild conditions was developed. A variety of highly substituted benzo[b]fluorenyl-containing S-alkyl phosphorothioates were successfully constructed in moderate to excellent yields. Furthermore, this protocol exhibited good functional group tolerance, a broad substrate scope, and potential practical applications, with water as the only byproduct. The reaction proceeded with allenyl thiophosphate as a key intermediate, followed by a Schmittel-type cyclization process to produce the target product.

Serum PLA2R antibody as a predictive biomarker for venous thromboembolism risk in primary membranous nephropathy.

BACKGROUND: Patients with nephrotic syndrome are at high risk of venous thromboembolism (VTE), especially for primary membranous nephropathy (PMN). The phospholipase A2 receptor (PLA2R) is a marker of primary membranous nephropathy activity. This study investigated the predictive value of PLA2R antibodies in PMN for VTE. METHODS: In this retrospective study, we included 97 PMN patients and evaluated the predictive value of serum PLA2R antibodies for VTE risk. Lower extremity venous ultrasound, renal vein ultrasound, or spiral computed tomography pulmonary arteriography were used to assess VTE events. Serum anti-PLA2R antibodies were detected by enzyme-linked immunosorbent assay (ELISA). The risk of VTE was stratified according to serum albumin levels. RESULTS: Twenty PMN patients (21%) had thromboembolic events. Eight (15%) of patients with serum albumin >25g/l developed VTE, 6 of whom were positive for serum PLA2R antibodies. Positive serum PLA2R antibodies were significantly associated with VTE events in patients with serum albumin >25g/l (p=0.01). Age, sex, blood creatinine, serum albumin, and 24-h urine protein levels were not statistically different between the two groups. Kaplan-Meier analysis using the log-rank test revealed anti-PLA2R positive membranous nephropathy patients had more probability of VTE events than anti-PLA2R negative patients. Univariate Cox proportional hazards analysis revealed that lnPLA2R-Ab is an unfavorable predictor for VTE events in patients with serum albumin >25g/l (hazard ratio (HR) 2.1, p=0.01). CONCLUSIONS: The PLA2R antibody was a risk predictor for thromboembolic events in patients with primary membranous nephropathy with serum albumin >25g/l.

Further Characterization of Fungal Halogenase RadH and Its Homologs.

RadH is one of the flavin-dependent halogenases that has previously exhibited promising catalytic activity towards hydroxycoumarin, hydroxyisoquinoline, and phenolic derivatives. Here, we evaluated new functional homologs of RadH and expanded its specificities for the halogenation of non-tryptophan-derived, heterocyclic scaffolds. Our investigation revealed that RadH could effectively halogenate hydroxyquinoline and hydroxybenzothiophene. Assay optimization studies revealed the need to balance the various co-factor concentrations and where a GDHi co-factor recycling system most significantly improves the conversion and efficiency of the reaction. A crystal structure of RadH was also obtained with a resolution of 2.4 Å, and docking studies were conducted to pinpoint the binding and catalytic sites for substrates.

Crescents proportions above 10% are associated with unfavorable kidney outcomes in IgA nephropathy patients with partial crescent formation.

PURPOSE: Whether different crescentic proportions determine the progression of IgA nephropathy (IgAN) with crescents in less than 50% of glomeruli remains controversial. We aimed to evaluate the relationship between different proportions of crescents and kidney outcomes in IgAN with partial crescent formation. METHODS: Patients diagnosed as IgAN, having at least two crescents and in less than 50% of glomeruli, were categorized into three groups: Group I (crescents in ≤10% of glomeruli), Group II (10%< crescents ≤25% of glomeruli) and Group III (crescents >25% of glomeruli). Baseline clinicopathological parameters were evaluated. The kidney endpoint was a composite of a ≥ 40% decline in the initial estimated glomerular filtration rate, end-stage kidney disease, and kidney disease-related death. RESULTS: Of 183 IgAN patients with crescents in less than 50% of glomeruli, baseline 24-hour urinary protein and immunosuppressive treatment varied among the three groups (p < 0.05). During a median follow-up of 57 months (interquartile range 28-86), 50 (27.3%) patients reached the composite outcome. Kaplan-Meier survival analysis revealed that kidney survival in Group II (p = 0.049) and Group III (p = 0.008) was significantly shorter than in Group I, with no significant difference between Group II and III (p = 0.2). After adjusting for clinical factors and MEST score based on the multivariate Cox regression analysis, a crescent proportion >10% (HR = 3.431, 95% CI 1.067-11.03, p = 0.039) was predictive of time to unfavorable kidney outcome, with model adjustments improving predictability (c-index: 0.817). CONCLUSION: The proportion of crescents reaching 10% of glomeruli in IgAN was identified as an independent risk factor for kidney survival.

Lectin Complement Pathway Activation is Associated with Massive Proteinuria in PLA2R-Positive Membranous Nephropathy: A Retrospective Study.

Introduction: Complement activation is highly involved in membranous nephropathy. Identifying the mechanism of the complement activation pathway carries crucial therapeutic implications yet remains controversial. This study explored lectin complement pathway activation in PLA2R-associated membranous nephropathy (MN). Methods: One hundred and seventy-six patients with biopsy-proven PLA2R-associated MN were enrolled in the retrospective study and divided into the remission group (24-hour urine protein <0.75g and serum albumin >35 g/L) and the nephrotic syndrome group. The clinical manifestation and C3, C4d, C1q, MBL, and B factor in renal biopsy tissues and C3, C4, and immunoglobulins in serum were evaluated. Results: Deposition of glomerular C3, C4d, and mannose-binding lectin (MBL) was significantly higher in the activated state than in the remission state in PLA2R-associated MN. MBL deposition was the risk factor for no remission. During follow-up, the persistent non-remission patients have significantly lower serum C3 levels. Conclusion: Activation of the lectin complement pathway in PLA2R-associated MN may contribute to proteinuria progression and disease activity.

A back propagation neural network approach to estimate the glomerular filtration rate in an older population.

BACKGROUND: The use of creatinine-based glomerular filtration rate (GFR)-estimating equations to evaluate kidney function in elderly individuals does not appear to offer any performance advantages. We therefore aimed to develop an accurate GFR-estimating tool for this age group. METHODS: Adults aged ≥ 65 years who underwent GFR measurement by technetium-99 m-diethylene triamine pentaacetic acid (99mTc-DTPA) renal dynamic imaging were included. Data were randomly split into a training set containing 80% of the participants and a test set containing the remaining 20% of the subjects. The Back propagation neural network (BPNN) approach was used to derive a novel GFR estimation tool; then we compared the performance of the BPNN tool with six creatinine-based equations (Chronic Kidney Disease-Epidemiology Collaboration [CKD-EPI], European Kidney Function Consortium [EKFC], Berlin Initiative Study-1 [BIS1], Lund-Malmö Revised [LMR], Asian modified CKD-EPI, and Modification of Diet in Renal Disease [MDRD]) in the test cohort. Three equation performance criteria were considered: bias (difference between measured GFR and estimated GFR), precision (interquartile range [IQR] of the median difference), and accuracy P30 (percentage of GFR estimates that are within 30% of measured GFR). RESULTS: The study included 1,222 older adults. The mean age of both the training cohort (n = 978) and the test cohort (n = 244) was 72 ± 6 years, with 544 (55.6%) and 129 (52.9%) males, respectively. The median bias of BPNN was 2.06 ml/min/1.73 m2, which was smaller than that of LMR (4.59 ml/min/1.73 m2; p = 0.03), and higher than that of the Asian modified CKD-EPI (-1.43 ml/min/1.73 m2; p = 0.02). The median bias between BPNN and each of CKD-EPI (2.19 ml/min/1.73 m2; p = 0.31), EKFC (-1.41 ml/min/1.73 m2; p = 0.26), BIS1 (0.64 ml/min/1.73 m2; p = 0.99), and MDRD (1.11 ml/min/1.73 m2; p = 0.45) was not significant. However, the BPNN had the highest precision IQR (14.31 ml/min/1.73 m2) and the greatest accuracy P30 among all equations (78.28%). At measured GFR < 45 ml/min/1.73 m2, the BPNN has highest accuracy P30 (70.69%), and highest precision IQR (12.46 ml/min/1.73 m2). The biases of BPNN and BIS1 equations were similar (0.74 [-1.55-2.78] and 0.24 [-2.58-1.61], respectively), smaller than any other equation. CONCLUSIONS: The novel BPNN tool is more accurate than the currently available creatinine-based GFR estimation equations in an older population and could be recommended for routine clinical use.

Clinical characteristics of membranous nephropathy with spontaneous remission: An analysis of 24 patients / Características clínicas de la nefropatía membranosa con remisión espontánea: análisis de 24 pacientes

Purpose To investigate the prognosis of patients with spontaneous remission (SR) of phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN).Patients and methods Patients diagnosed with MN were recruited after examining their renal biopsy in the Renal Department of China-Japan Friendship Hospital between January 2015 and September 2021. Among them, 24 patients with SR were included in this study and follow-up. Results Twenty-four patients diagnosed with SR of PLA2R-associated MN were recruited; 11 were male, and 13 were female, with a mean age of 49.5±14.5 years (range, 30–77 years). The initial 24-hour urinary total protein and serum albumin levels were 0.29±0.14g/d and 37.5±4.4g/L, respectively, and the initial serum creatinine was 65.0±15.8μmol/L. During the follow-up of 33.9±19.1 months (range, 6–73 months), 22 (91.7%) patients maintained remission; however, one patient had impaired renal function due to acute coronary syndrome and coronary angiography findings, and one patient experienced a repeated relapse caused by respiratory tract infection, at 50 and 70 months. A systematic review of the relevant literature was conducted, and records of patients with SR of PLA2R-associated MN were retrieved from 16 case reports or case series with a total of 97 cases. ConclusionsMost patients with SR of MN had a promising long-term prognosis, with only a few cases of relapse. (AU)

Objetivo Investigar el pronóstico de los pacientes con remisión espontánea en la nefropatía membranosa (MN, por sus siglas en inglés) asociada al receptor fosfolipasa A2 (PLA2R). Pacientes y métodos Pacientes con MN diagnosticados por biopsia renal en el Departamento Renal del China-Japan Friendship Hospital entre enero de 2015 y septiembre de 2021. Entre ellos, 24 pacientes con remisión espontánea fueron reclutados y seguidos. Resultados Se reclutaron 24 pacientes con MN en remisión espontánea asociada a PLA2R; 11 varones y 13 mujeres, con una edad media de 49,5±14,5 años (rango: 30-77 años) en el momento del diagnóstico. La proteína total y la albúmina sérica en orina de 24h iniciales fueron de 0,29±0,14 y 37,5±4,4g/l, respectivamente; la creatinina sérica inicial fue de 65,0±15,8μmol/l. Durante el seguimiento de 33,9±19,1 (rango: 6-73) meses, 22 pacientes (91,7%) mantienen la remisión. Un paciente presentó insuficiencia renal por síndrome coronario agudo y angiografía coronaria. Otro paciente tuvo una recaída causada por una infección del tracto respiratorio 2 veces, a los 50 y 70 meses. Se realizó una revisión sistemática de la literatura. Los pacientes con MN asociada con PLA2R en remisión espontánea se recuperaron en 16 informes o series de casos, de 97 casos en total. ConclusionesLa mayoría de los pacientes con MN en remisión espontánea tuvieron un pronóstico prometedor a largo plazo, mientras que solo unos pocos casos tuvieron recaída. (AU)

Direct Synthesis of Benzo[b]fluorenyl Thiophosphates via Tandem Cyclization of Diynols with (RO)2P(O)SH.

A general and metal-free protocol for the construction of benzo[b]fluorenyl thiophosphates was developed through the cascade cyclization of easily prepared diynols and (RO)2P(O)SH, with water as the only byproduct. The novel transformation involved the allenyl thiophosphate as the key intermediate, followed by Schmittel-type cyclization to achieve the desired products. Notably, (RO)2P(O)SH acted not only as a nucleophile but also as an acid-promoter to initiate the reaction.

Clinical characteristics of membranous nephropathy with spontaneous remission: An analysis of 24 patients.

PURPOSE: To investigate the prognosis of patients with spontaneous remission (SR) of phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN). PATIENTS AND METHODS: Patients diagnosed with MN were recruited after examining their renal biopsy in the Renal Department of China-Japan Friendship Hospital between January 2015 and September 2021. Among them, 24 patients with SR were included in this study and follow-up. RESULTS: Twenty-four patients diagnosed with SR of PLA2R-associated MN were recruited; 11 were male, and 13 were female, with a mean age of 49.5±14.5 years (range, 30-77 years). The initial 24-hour urinary total protein and serum albumin levels were 0.29±0.14g/d and 37.5±4.4g/L, respectively, and the initial serum creatinine was 65.0±15.8µmol/L. During the follow-up of 33.9±19.1 months (range, 6-73 months), 22 (91.7%) patients maintained remission; however, one patient had impaired renal function due to acute coronary syndrome and coronary angiography findings, and one patient experienced a repeated relapse caused by respiratory tract infection, at 50 and 70 months. A systematic review of the relevant literature was conducted, and records of patients with SR of PLA2R-associated MN were retrieved from 16 case reports or case series with a total of 97 cases. CONCLUSIONS: Most patients with SR of MN had a promising long-term prognosis, with only a few cases of relapse.

Protein restriction for diabetic kidney disease.

BACKGROUND: Diabetic kidney disease (DKD) continues to be the leading cause of kidney failure across the world. For decades dietary protein restriction has been proposed for patients with DKD with the aim to retard the progression of chronic kidney disease (CKD) towards kidney failure. However, the relative benefits and harms of dietary protein restriction for slowing the progression of DKD have not been addressed. OBJECTIVES: To determine the efficacy and safety of low protein diets (LPD) (0.6 to 0.8 g/kg/day) in preventing the progression of CKD towards kidney failure and in reducing the incidence of kidney failure and death (any cause) in adult patients with DKD. Moreover, the effect of LPD on adverse events (e.g. malnutrition, hyperglycaemic events, or health-related quality of life (HRQoL)) and compliance were also evaluated. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 17 November 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs in which adults with DKD not on dialysis were randomised to receive either a LPD (0.6 to 0.8 g/kg/day) or a usual or unrestricted protein diet (UPD) (≥ 1.0 g/kg/day) for at least 12 months. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies and extracted data. Summary estimates of effect were obtained using a random-effects model. Results were summarised as risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) or standardised MD (SMD) with 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: We identified eight studies involving 486 participants with DKD. The prescribed protein intake in the intervention groups ranged from 0.6 to 0.8 g/kg/day. The prescribed protein intake in the control groups was ≥ 1.0 g/kg/day, or a calculated protein intake ≥ 1.0 g/kg/day if data on prescribed protein intake were not provided. The mean duration of the interventions was two years (ranging from one to five years). Risks of bias in most of the included studies were high or unclear, most notably for allocation concealment, performance and detection bias. All studies were considered to be at high risk for performance bias due to the nature of the interventions. Most studies were not designed to examine death or kidney failure. In low certainty evidence, a LPD may have little or no effect on death (5 studies, 358 participants: RR 0.38, 95% CI 0.10 to 1.44; I² = 0%), and the number of participants who reached kidney failure (4 studies, 287 participants: RR 1.16, 95% CI 0.38 to 3.59; I² = 0%). Compared to a usual or unrestricted protein intake, it remains uncertain whether a LPD slows the decline of glomerular filtration rate over time (7 studies, 367 participants: MD -0.73 mL/min/1.73 m²/year, 95% CI -2.3 to 0.83; I² = 53%; very low certainty evidence). It is also uncertain whether the restriction of dietary protein intake impacts on the annual decline in creatinine clearance (3 studies, 203 participants: MD -2.39 mL/min/year, 95% CI -5.87 to 1.08; I² = 53%). There was only one study reporting 24-hour urinary protein excretion. In very low certainty evidence, a LPD had uncertain effects on the annual change in proteinuria (1 study, 80 participants: MD 0.90 g/24 hours, 95% CI 0.49 to 1.31). There was no evidence of malnutrition in seven studies, while one study noted this condition in the LPD group. Participant compliance with a LPD was unsatisfactory in nearly half of the studies. One study reported LPD had no effect on HRQoL. No studies reported hyperglycaemic events. AUTHORS' CONCLUSIONS: Dietary protein restriction has uncertain effects on changes in kidney function over time. However, it may make little difference to the risk of death and kidney failure. Questions remain about protein intake levels and compliance with protein-restricted diets. There are limited data on HRQoL and adverse effects such as nutritional measures and hyperglycaemic events. Large-scale pragmatic RCTs with sufficient follow-up are required for different stages of CKD.

Beraprost Sodium Delays the Decline of Glomerular Filtration Rate in Patients with Diabetic Nephropathy: A Retrospective Study.

INTRODUCTION: To investigate the reno-protective effect of beraprost sodium (BPS) in patients with diabetic nephropathy (DN). METHODS: We retrospectively analyzed patients with DN hospitalized in China-Japan Friendship Hospital from January 2015 to December 2021 who received combination of conventional treatment and BPS (120 ug/day) therapy. We selected patients with DN matched in age and estimated glomerular filtration rate (eGFR) as controls, who received only conventional therapy. Baseline information and clinical variables at each follow-up visit were collected from all patients. The changes of clinical variables were compared between the two groups before and after treatment. RESULTS: A total of 50 patients with DN met the inclusion and exclusion criteria, with 25 patients in each group. The baseline characteristics of the two groups have no significant difference (p > 0.05). Serum albumin levels after treatment were improved in both groups, but the improvement was statistically significant only in BPS group (35.5-39.8 g/l, p < 0.001). The eGFR worsened significantly in both groups (p = 0.009 and p = 0.001). However, the decline of eGFR was less in BPS group than that in control group (- 9.8 vs. - 16.7 ml/min/1.73 m2, p = 0.037). In the subgroup analysis, 30 patients received 3-12 months treatment and 20 patients received more than 12 months treatment. During the 3-12 months treatment period, serum creatinine and eGFR in the control group were significantly worsened compared with those before treatment (p = 0.019 and p = 0.03), but in the BPS group they were relatively stable (p > 0.05). After more than 12 months treatment, although the serum creatinine and eGFR were significantly worsened in both groups (p < 0.05), the decline of eGFR was less in BPS group than that in control group (- 10.1 vs. - 25.9 ml/min/1.73 m2, p = 0.045). CONCLUSIONS: Combination of conventional treatment and BPS therapy delays the decline of eGFR in patients with DN in the long term.