Asymmetric 2,3-Addition of Sulfinylamines with Arylboronic Acids Enabled by Nickel Catalysis.

Sulfinamides have been widely used in organic synthesis, with research on their preparation spanning more than a century. Despite advancements in catalytic methodologies, creating sulfur stereocenters within these molecules remains a significant challenge. In this study, we present an effective and versatile method for synthesizing a diverse range of S-chirogenic sulfinamides through catalytic asymmetric aryl addition to sulfinylamines. By utilizing a nickel complex as a catalyst, this process exhibits impressive enantioselectivity and can incorporate various arylboronic acids at the sulfur position. The resulting synthetic sulfinamides are stable and highly adaptable, allowing for their conversion to a variety of sulfur-containing compounds. Our study also incorporates detailed experimental and computational studies to elucidate the reaction mechanism and factors influencing enantioselectivity.

Chromium- and Metal-Reductant-Free Asymmetric Nozaki-Hiyama-Kishi (NHK) Reaction Enabled by Metallaphotoredox Catalysis.

Chiral allylic alcohols are highly prized in synthetic chemistry due to their versatile reactivity stemming from both alkenyl and hydroxyl functionalities. While the Nozaki-Hiyama-Kishi (NHK) reaction is a widely used method for the synthesis of allylic alcohols, it suffers from drawbacks such as the use of toxic chromium salts, high amounts of metal reductants, and poor enantiocontrol. To address these limitations, we present a novel approach involving a metallaphotoredox-catalyzed asymmetric NHK reaction for the production of chiral allylic alcohols. This method marries alkenyl (pseudo)halides with aldehydes, leveraging a synergistic blend of a chiral nickel catalyst and a photocatalyst. This innovative technique enables both oxidative addition and insertion just using nickel, diverging significantly from the conventional NHK reaction pathway mediated by nickel and chromium salts. The adoption of this methodology holds immense promise for crafting a spectrum of intricate compounds, particularly those of significance in pharmaceuticals. Detailed experimental investigations have shed light on the metallaphotoredox process, further enhancing our understanding and enabling further advancements.

Clinicopathological features and outcome in elderly patients with idiopathic membranous nephropathy.

BACKGROUND: Idiopathic membranous nephropathy (IMN) is the leading cause of nephrotic syndrome in the elderly. The treatment of idiopathic membranous nephropathy is quite challenging due to the particularity of elderly patients. This study intends to investigate the clinicopathological characteristics and initial therapeutic effect of idiopathic membranous nephropathy among elderly patients. METHODS: A retrospective study of 67 elderly patients (58.2% male, median age 69.0 years, range, 65-83 years) with biopsy-proven membranous nephropathy was conducted at Guangdong Provincial People's Hospital from 2016 to 2020. Data on clinicopathological characteristics and initial therapeutic effects were analyzed. RESULTS: Of the 67 patients, the mean eGFR of overall patients was 66.49 mL/min/1.73m2 while the median urine protein-to-creatinine ratio (uPCR) and urine albumin-to-creatinine ratio (uACR) was 5676.73 mg/g and 2951.56 mg/g, respectively. Pathological data revealed that the membranous Churg's stage II was the most frequent (71.64%). Moreover, glomerular PLA2R antigen fluorescence intensity of (+) and IgG4 antigen fluorescence intensity of (++) were detected in 63.6% and 86.4% of all patients, respectively. Overall, 44 patients, accounting for 65.7%, achieved remission including complete remission and partial remission within 1 year after renal biopsy. Compared with a non-remission group, the levels of uPCR (6274.6 vs. 3235.6 mg/g, p = 0.007) and uACR (3433.6 vs. 1773.2 mg/g, p = 0.017) were significantly higher in remission group. The proportion of immunosuppressive therapy in the remission group was also higher (86.4% vs. 30.4%, p < 0.01). Compared with conservative treatment, patients with combined treatment with glucocorticoid and cyclophosphamide (CTX) or glucocorticoid and calcineurin inhibitor (CNIs) achieved higher remission rate (glucocorticoid plus cyclophosphamide vs. conservative treatment, 84.6% vs. 27.3%, p = 0.001; glucocorticoid plus calcineurin inhibitor vs. conservative treatment, 88.0% vs. 27.3%, p < 0.001). Further analysis showed that compared with patients who underwent conservative treatment, the proportion of males, the levels of uPCR, uACR, BUN, Scr, CysC and PLA2R antigen-positive staining rate in kidney biopsy were higher in those who underwent combined treatment with glucocorticoid and CTX, while the levels of eGFR, TP and ALB were lower (p < 0.05). In addition, patients who received combined treatment with glucocorticoid and CNIs had higher levels of uPCR, uACR, TC and lower levels of TP, ALB than those who received conservative treatment (p < 0.05). Moreover, there were no statistically significant differences in the 1-year progression rate in eGFR between the immunosuppressive treatment group and conservative treatment group (3.3 vs. 0.2 ml/min/1.73m2, p = 0.852). CONCLUSIONS: Most elderly patients diagnosed with IMN had multiple comorbidities, and the membranous Churg's stage II was most common. The glomerular PLA2R and IgG4 antigen deposition were frequently detected accompanied by glomerulosclerosis and severe tubulointerstitial injury. For high-risk elderly patients with severe proteinuria, early initial immunosuppressive therapy could achieve a higher urinary protein remission rate. Therefore, it is crucial for clinicians to balance the risks and benefits of immunosuppressive therapy based on clinical and pathological characteristics and develop individualized treatment regimens for elderly patients with IMN.

Metal-Free Stereoconvergent C-H Borylation of Enamides.

Enamides, functional derivatives of enamines, play a significant role as synthetic targets. However, the stereoselective synthesis of these molecules has posed a longstanding challenge in organic chemistry, particularly for acyclic enamides that are less thermodynamically stable. In this study, we present a general strategy for constructing ß-borylenamides by C-H borylation, which provides a versatile platform for generating the stereodefined enamides. Our approach involves the utilization of metalloid borenium cation, generated through the reaction of BBr3 and enamides in the presence of two different additives, avoiding any exogenous catalyst. Importantly, the stereoconvergent nature of this methodology allows for the use of starting materials with mixed E/Z configurations, thus highlighting the unique advantage of this chemistry. Mechanistic investigations have shed light on the pivotal roles played by the two additives, the reactive boron species, and the phenomenon of stereoconvergence.

M2a and M2b macrophages predominate in kidney tissues and M2 subpopulations were associated with the severity of disease of IgAN patients.

M2 macrophages play important roles during the injury and repair phases in kidney. Our aims are to investigate the distribution of M2 subpopulations and the correlation with clinicopathological features of IgA nephropathy (IgAN) patients. In this study, renal samples from 49 IgAN patients were detected by immunofluorescence. The markers of M2 macrophages, including M2a (CD206+/CD68+), M2b (CD86+/CD68+) and M2c (CD163+/CD68+) were identified. We found M2a and M2b macrophages were the predominant subpopulations in kidney tissues of IgAN. M2a macrophages were mainly distributed in tubulointerstitium with renal lesions like segmental glomerulosclerosis and tubular atrophy/interstitial fibrosis. However, there were larger numbers of M2c in glomeruli with minor lesions. Moreover, M2a and M2c macrophages were inversely correlated with the clinical and pathologic features, respectively. These results suggest M2 subpopulations were involved in the progression of IgAN, and M2a and M2c macrophages might show different properties to participate in the pathogenesis of IgAN.

Effects of dehydroepiandrosterone supplementation on mice with diminished ovarian reserve.

Dehydroepiandrosterone (DHEA) has been used to improve the pregnancy rate in women with diminished ovarian reserve(DOR) during in vitro fertilization. We aimed to validate the effects of DHEA and identify the possible mechanisms. We constructed a mice model with DOR and analyzed the hormone parameters and follicle counts. In vivo experiment, FSH and LH concentrations in the serum were significantly elevated in the DOR group. However, the FSH and LH concentrations were partially reversed in the DOR + DHEA group. The E2, AMH and INHB were down-regulated in the DOR group and reversed in the DOR + DHEA group. Our study supported evidences that DHEA might modulate the hormone receptors in the ovary and hormone secretions to the peripheral circulation to regulate the ovary reserve functions.

Alternatively Activated Macrophages are Associated with Prostate Volume and Lower Urinary Tract Symptoms Severity of Patients with Benign Prostate Hyperplasia.

BACKGROUND: Recent studies show that alternatively activated macrophages (AAMs) are involved in tissue remodeling and fibrosis. However, the relationship between AAMs and the development of benign prostate hyperplasia (BPH) is unclear. The aim of this study is to investigate the correlation among AAMs, prostate volume, and lower urinary tract symptoms (LUTS) severity of benign prostate hyperplasia (BPH) patients. METHODS: Patients who underwent transurethral incision of the prostate (TUIP) for BPH were recruited and international prostatic symptom scores (IPSS) were assessed before the operations. Patients were divided into two groups: small (< 40 mL) and large prostate (≥ 40 mL) groups. Total macrophages (CD68) and AAMs (co-localization of CD68 and CD206) were analyzed by immunofluorescence. Prostate volume, post-voided residual volume (PVR), maximal (Qmax) and average (Qave) urinary flow rate were measured. We compared AAMs and clinical features between groups and analyzed the relationship of AAMs and these clinical parameters. RESULTS: A total of 42 patients diagnosed with BPH were recruited. The numbers of AAMs in prostate tissues of BPH patients with small prostate (n = 20) (5.15 ± 2.32 cells/HP) were significantly lower than those of large prostate (n = 22) (7.73 ± 2.83 cells/HP) (p < 0.05). Moreover, percentages of AAMs (AAMs/total macrophages) of small prostate patients (17.28 ± 6.62%) were lower than those of large prostate patients (23.30 ± 8.66%) (p < 0.05). Pearson's correlation analysis showed the numbers of AAMs were significantly positively correlated with prostate volume (r = 0.509, p < 0.01) and international prostatic symptom score (r = 0.344, p < 0.05). Percentages of AAMs were positively correlated with prostate volume (r = 0.447, p < 0.01). CONCLUSIONS: AAMs are associated the degree of BPH and the severity of LUTS, which indicates that AAMs may play an important role in development of BPH.

Risk Factors and Prognosis of Cardiorenal Syndrome Type 1 in Elderly Chinese Patients: A Retrospective Observational Cohort Study.

BACKGROUND/AIMS: Cardiorenal syndrome type 1 (CRS1) is a syndrome characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). The aims of this study were to investigate the risk factors and the prognosis of CRS1 in elderly patients. METHODS: A total of 312 elderly patients (≥60 years old) with acute heart failure (AHF) were studied. They were assigned as CRS1 (suffered from in-hospital AKI) or NCRS1 (without AKI) group. Clinical and laboratory data were recorded. Univariate and multivariate analysis were performed to clarify the risk factors for occurrence and mortality of CRS1 in this cohort. RESULTS: Incidence of CRS1 was 52.56%. Basic estimated glomerular filtration (eGFR <60 ml/(min.1.73m2) and use of diuretics were associated with the higher risk of CRS1 in elderly patients (OR=2.239, P=0.025; OR=2.555, P=0.001; respectively). Whereas higher concentration of serum albumin was protective factor for them (OR=0.907, P=0.007). The in-hospital mortality of CRS1 was 23.2%. Dialysis, use of beta blockers or diuretics were associated with all-cause death of CRS1 patients (OR=10.407, P<0.001; OR=0.312, P=0.011; OR=0.345, P=0.040; respectively). The in-hospital mortality of AHF patients was 13.1%. Higher Charlson comorbidity index, occurrence of CRS1 and dialysis were risk factors for in-hospital mortality of AHF patients (OR=4.723, P=0.041; OR=6.096, P=0.008; OR=18.743, P<0.001; respectively). CONCLUSIONS: Incidence of CRS1 in elderly patients is relatively high and associated with poor outcome. Reduced basic eGFR, lower serum albumin and use of diuretics are risk factors for the occurrence of CRS1 in elderly patients, while use of diuretics, beta blockers and dialysis during hospitalization are predictors of in-hospital mortality in patients with CRS1. These results above suggest that more suitable treatments for the elderly with CRS1 might be needed.

A retrospective analysis of kidney function and risk factors by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation in elderly Chinese patients.

Chronic kidney disease accounts for much of the increased mortality, especially in the elder population. The prevalence of this disease is expected to increase significantly as the society ages. Our aim was to evaluate the kidney function and risk factors of reduced renal function among elderly Chinese patients. This study retrospectively collected clinical data from a total of 1062 inpatients aged 65 years or over. Estimated glomerular filtration rate (eGFR) was calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Renal function and risk factors were also analyzed. For all 1062 subjects, the mean eGFR was 71.0 ± 24.8 mL/min/1.73 m(2), and the incidence rates of reduced renal function, proteinuria, hematuria and leukocyturia were 31.1%, 11.8%, 6.6% and 8.7%, respectively. The eGFR values were 83.4 ± 28.4, 72.2 ± 22.9, 67.8 ± 24.3 and 58.8 ± 29.1 mL/min/1.73 m(2) in the groups of 60-69, 70-79, 80-89 and ≥90 years age group (F = 15.101, p = 0.000), respectively; while the incidences of reduced renal function were 12.8%, 27.0%, 37.8% and 51.7% (χ(2) = 36.143, p = 0.000). Binary logistic regression analysis showed that hyperuricemia (OR = 4.62, p = 0.000), proteinuria (OR = 3.96, p = 0.000), urinary tumor (OR = 2.92, p = 0.015), anemia (OR = 2.45, p = 0.000), stroke (OR = 1.96, p = 0.000), hypertension (OR = 1.83, p = 0.006), renal cyst (OR = 1.64, p = 0.018), female (OR = 1.54, p = 0.015), coronary artery disease (OR = 1.53, p = 0.008) and age (OR = 1.05, p = 0.000) were the risk factors of reduced renal function. In conclusion, eGFR values decreased by age, while the incidence of reduced renal function, proteinuria, hematuria and leukocyturia increased with age. Treatment and control of comorbidities may slow the decline of renal function in elderly patients.

The impact of low oocyte maturity ratio on blastocyst euploidy rate: a matched retrospective cohort study.

OBJECTIVE: To investigate the association between a low oocyte maturity ratio from in vitro fertilization cycle and blastocyst euploidy. METHODS: A total of 563 preimplantation genetic testing (PGT) cycles (PGT cycles with chromosomal structural rearrangements were excluded) were performed between January 2021 and November 2022 at our center (average oocyte maturity rate: 86.4% ± 14.6%). Among them, 93 PGT cycles were classified into the low oocyte maturity rate group (group A, < mean - 1 standard deviation [SD]), and 186 PGT cycles were grouped into the average oocyte maturity rate group (group B, mean ± 1 SD). Group B was 2:1 matched with group A. Embryological, blastocyst ploidy, and clinical outcomes were compared between the two groups. RESULTS: The oocyte maturity (metaphase II [MII oocytes]), MII oocyte rate, and two pronuclei (2PN) rates were significantly lower in group A than in group B (5.2 ± 3.0 vs. 8.9 ± 5.0, P = 0.000; 61.6% vs. 93.0%, P = 0.000; 78.7% vs. 84.8%, P = 0.002, respectively). In group A, 106 of 236 blastocysts (44.9%) that underwent PGT for aneuploidy were euploid, which was not significantly different from the rate in group B (336/729, 46.1%, P = 0.753). However, euploid blastocysts were obtained only in 55 cycles in group A (55/93, 59.1%), which was lower than the rate in group B (145/186, 78.0%, P = 0.001). The clinical pregnancy rate in group B (73.9%) was higher than that in group A (58.0%) (P = 0.040). CONCLUSION: Our results suggest that a low oocyte maturity ratio is not associated with blastocyst euploidy but is associated with fewer cycles with euploid blastocysts for transfer, lower 2PN rates, and lower clinical pregnancy rates.