NLRP4E regulates actin cap formation through SRC and CDC42 during oocyte meiosis.

BACKGROUND: Members of the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing (NLRP) family regulate various physiological and pathological processes. However, none have been shown to regulate actin cap formation or spindle translocation during the asymmetric division of oocyte meiosis I. NLRP4E has been reported as a candidate protein in female fertility, but its function is unknown. METHODS: Immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR), and western blotting were employed to examine the localization and expression levels of NLRP4E and related proteins in mouse oocytes. small interfering RNA (siRNA) and antibody transfection were used to knock down NLRP4E and other proteins. Immunoprecipitation (IP)-mass spectrometry was used to identify the potential proteins interacting with NLRP4E. Coimmunoprecipitation (Co-IP) was used to verify the protein interactions. Wild type (WT) or mutant NLRP4E messenger RNA (mRNA) was injected into oocytes for rescue experiments. In vitro phosphorylation was employed to examine the activation of steroid receptor coactivator (SRC) by NLRP4E. RESULTS: NLRP4E was more predominant within oocytes compared with other NLRP4 members. NLRP4E knockdown significantly inhibited actin cap formation and spindle translocation toward the cap region, resulting in the failure of polar body extrusion at the end of meiosis I. Mechanistically, GRIN1, and GANO1 activated NLRP4E by phosphorylation at Ser429 and Thr430; p-NLRP4E is translocated and is accumulated in the actin cap region during spindle translocation. Next, we found that p-NLRP4E directly phosphorylated SRC at Tyr418, while p-SRC negatively regulated p-CDC42-S71, an inactive form of CDC42 that promotes actin cap formation and spindle translocation in the GTP-bound form. CONCLUSIONS: NLRP4E activated by GRIN1 and GANO1 regulates actin cap formation and spindle translocation toward the cap region through upregulation of p-SRC-Tyr418 and downregulation of p-CDC42-S71 during meiosis I.

Platycodon grandiflorum saponins: Ionic liquid-ultrasound-assisted extraction, antioxidant, whitening, and antiaging activity.

This study explored the use of ionic liquid-ultrasound (ILU)-assisted extraction to enhance the extraction rate of Platycodon grandiflorum saponins (PGSs), and the content, extraction mechanism, antioxidant activity, whitening, and antiaging activity of PGSs prepared using ILU, ultrasound-water, thermal reflux-ethanol, and cellulase hydrolysis were compared. The ILU method particularly disrupted the cell wall, improved PGS extraction efficiency, and yielded a high total saponin content of 1.45 ± 0.02 mg/g. Five monomeric saponins were identified, with platycodin D being the most abundant at 1.357 mg/g. PGSs displayed excellent in vitro antioxidant activity and exhibited inhibitory effects on tyrosinase, elastase, and hyaluronidase. The results suggest that PGSs may have broad antioxidant, skin-whitening, and antiaging potential to a large extent. Overall, this study provided valuable insights into the extraction, identification, and bioactivities of PGSs, which could serve as a reference for future development and application of these compounds in the functional foods industry.

Polydopamine-modified konjac glucomannan scaffold with sustained release of vascular endothelial growth factor to promote angiogenesis.

The fabrication of scaffolds capable of the sustained release of the vascular endothelial growth factor (VEGF) to promote angiogenesis in long time remains a challenge in tissue engineering. Here, we report a facile approach for effectively fabricating a bioactive scaffold that gradually releases VEGF to promote angiogenesis. The scaffold was fabricated by coating polydopamine (PDA) on a konjac glucomannan (KGM) scaffold, followed by the surface immobilization of VEGF with PDA. The resulting VEGF-PDA/KGM scaffold, with a porous and interconnected microstructure (392 µm pore size with 84.80 porosity), combined the features of long-term biodegradability (10 weeks with 51 % degradation rate), excellent biocompatibility, and sustained VEGF release for up to 21 days. The bioactive VEGF-PDA/KGM scaffold exhibited multiple angiogenic activities over time, as confirmed by in vivo and in vitro experiments. For example, the scaffold significantly promoted the attachment and proliferation of human umbilical vein endothelial cells and the formation of vascular tubes in vitro. Moreover, the in vivo results demonstrated the formation and maturation of blood vessels after subcutaneous implantation in rats for four weeks. This promising strategy is a feasible approach for producing bioactive materials that can induce angiogenesis in vivo. These findings provide a new avenue for designing and fabricating biocompatible and long-term biodegradable scaffolds for sustained VEGF release to facilitate angiogenesis.

Ultrashort echo time MRI detects significantly lower collagen but higher pore water in the tibial cortex of female patients with osteopenia and osteoporosis.

Ultrashort echo time (UTE) MRI can quantify the major proton pool densities in cortical bone, including total (TWPD), bound (BWPD), and pore water (PWPD) proton densities, as well as the macromolecular proton density (MMPD), associated with the collagen content, which is calculated using macromolecular fraction (MMF) from UTE magnetization transfer (UTE-MT) modeling. This study aimed to investigate the differences in water and collagen contents in tibial cortical bone, between female osteopenia (OPe) patients, osteoporosis (OPo) patients, and young participants (Young). Being postmenopausal and above 55 years old were the inclusion criteria for OPe and OPo groups. The tibial shaft of fourteen OPe (72.5 ± 6.8 years old), thirty-one OPo (72.0 ± 6.4 years old), and thirty-one young subjects (28.0 ± 6.1 years old) were scanned using a knee coil on a clinical 3 T scanner. Basic UTE, inversion recovery UTE, and UTE-MT sequences were performed. Investigated biomarkers were compared between groups using Kruskal-Wallis test. Spearman's correlation coefficients were calculated between the total hip dual-energy x-ray absorptiometry (DXA) T-score and UTE-MRI results. MMF, BWPD, and MMPD were significantly lower in OPo patients than in the young group. Whereas T1, TWPD, and PWPD were significantly higher in OPo patients. The largest OPo/Young average percentage differences were found in MMF (41.9%), PWPD (103.5%), and MMPD (64.0%). PWPD was significantly higher (50.7%), while BWPD was significantly lower (16.4%) in OPe than the Young group on average. MMF was found to be significantly lower (27%) in OPo patients compared with OPe group. T1, MMF, TWPD, PWPD, and MMPD values significantly correlated with the total hip DXA T-scores (provided by the patients and only available for OPe and OPo patients). DXA T-score showed the highest correlations with PWPD (R = 0.55) and MMF (R = 0.56) values. TWPD, PWPD, and MMF estimated using the UTE-MRI sequences were recommended to evaluate individuals with OPe and OPo.

Ultrashort echo time (UTE) is an MRI technique that can quantify the water and collagen content of cortical bone. Water in the bone can be found residing in pores (pore water) or bound to the bone matrix (bound water). We investigated the differences in water and collagen contents of tibial cortical bone, between female osteopenia patients, osteoporosis patients, and young participants. Bound water and collagen contents were significantly lower in osteoporosis patients than in the young group. Whereas total water and pore water contents were significantly higher in osteoporosis patients. Pore water was significantly higher, while bound water was significantly lower in osteopenia than in the Young group. Collagen content was found to be significantly lower in osteoporosis patients compared with the osteopenia group. The estimated water and collagen contents were significantly correlated with the total hip bone densitometry measures in the patients.

Long-term surgical outcomes of bile duct tumor thrombus versus portal vein tumor thrombus for hepatocellular carcinoma: a propensity score matching analysis.

Background: Portal vein tumor thrombus (PVTT) seriously affects the prognosis of hepatocellular carcinoma (HCC). However, whether bile duct tumor thrombus (BDTT) significantly affects the prognosis of HCC as much as PVTT remains unclear. We aimed to compare the long-term surgical outcomes of HCC with macroscopic PVTT (macro-PVTT) and macroscopic BDTT (macro-BDTT). Methods: The data of HCC patients with macro-BDTT or macro-PVTT who underwent hemihepatectomy were retrospectively reviewed. A propensity score matching (PSM) analysis was performed to reduce the baseline imbalance. The recurrence-free survival (RFS) and overall survival (OS) rates were compared between the cohorts. Results: Before PSM, the PVTT group had worse RFS and OS rates than the BDTT group (P = 0.043 and P = 0.008, respectively). Multivariate analyses identified PVTT (hazard ratio [HR] = 1.835, P = 0.016) and large HCC (HR = 1.553, P = 0.039) as independent risk factors for poor OS and RFS, respectively. After PSM, the PVTT group had worse RFS and OS rates than the BDTT group (P = 0.037 and P = 0.004, respectively). The 3- and 5-year OS rates were significantly higher in the BDTT group (59.5% and 52.1%, respectively) than in the PVTT group (33.3% and 20.2%, respectively). Conclusion: Aggressive hemihepatectomy provides an acceptable prognosis for HCC patients with macro-BDTT. Furthermore, the long-term surgical outcomes of HCC patients with macro-BDTT were significantly better than those of HCC patients with macro-PVTT.

Screening of efficient salicylaldoxime reactivators for DFP and paraoxon-inhibited acetylcholinesterase.

Previously we reported two salicylaldoxime conjugates (L7R3 and L7R5) showing equal or even higher reactivating efficiency for both organophosphorus nerve agent and pesticide inhibited acetylcholinesterase in comparison to obidoxime and HI-6. In this study, L7R3 and L7R5 were selected as lead compounds and refined by employing a fragment-based drug design strategy, and a total of 32 novel salicylaldoxime conjugates were constructed and screened for DFP and paraoxon inhibited acetylcholinesterase. The findings demonstrate that the conjugate L73R3, which contains a 4-nitrophenyl group, exhibited a higher reactivation efficacy against paraoxon-inhibited acetylcholinesterase compared to obidoxime and HI-6. It was confirmed that the combination of a 4-pyridinyl or 4-nitrophenyl peripheral site ligand, a piperazine linker and a methyl or chloro-substituted salicylaldoxime could construct efficient nonquaternary oxime reactivators. The results hold promise for developing a new generation of highly effective antidotes for organophosphate poisoning.

Inclusion of reeling wastewater-derived sericin peptides in high-protein nutrition bars for antihardening and storage stability.

The utilization of agroindustrial wastes to enrich food protein resources and the exploration of their broader applications are crucial for addressing the food crisis and achieving sustainable development goals. In this study, reeling wastewater-derived sericin was hydrolyzed using papain and trypsin to prepare sericin peptide (SRP) and was used as an antihardening ingredient of high-protein nutrition bars (HPNBs). The mechanism of the antihardening effect of SRP was elucidated by investigating the content of advanced glycation end products and protein oxidation products (carbonyl and free sulfhydryl), and the molecular weight change of HPNBs during storage before and after the addition of SRP. Our results confirmed the fortification of HPNBs with SRP, which is beneficial for the promotion and expansion of sericin applications in the food industry, with positive implications for the rational utilization of protein resources and the enrichment of food protein sources.

Wearable smart contact lenses: A critical comparison of three physiological signals outputs for health monitoring.

Smart contact lenses (SCLs) have been considered as novel wearable devices for out-of-hospital and self-monitoring applications. They are capable of non-invasively and continuously monitoring physiological signals in the eyes, including vital biophysical (e.g., intraocular of pressure, temperature, and electrophysiological signal) and biochemical signals (e.g., pH, glucose, protein, nitrite, lactic acid, and ions). Recent progress mainly focuses on the rational design of wearable SCLs for physiological signal monitoring, while also facilitating the treatment of various ocular diseases. It covers contact lens materials, fabrication technologies, and integration methods. We also highlight and discuss a critical comparison of SCLs with electrical, microfluidic, and optical signal outputs in health monitoring. Their advantages and disadvantages could help researchers to make decisions when developing SCLs with desired properties for physiological signal monitoring. These unique capabilities make SCLs promising diagnostic and therapeutic tools. Despite the extensive research in SCLs, new technologies are still in their early stages of development and there are a few challenges to be addressed before these SCLs technologies can be successfully commercialized particularly in the form of rigorous clinical trials.

Metabolomics and HS-SPME-GC-MS-based analysis of quality succession patterns and flavor characteristics changes during the fermentation of Lycium barbarum and Polygonatum cyrtonema compound wine.

This work set out to investigate how the physicochemical markers, volatiles, and metabolomic characteristics of mixed fermented the fermentation of Lycium barbarum and Polygonatum cyrtonema compound wine (LPCW) from S. cerevisine RW and D. hansenii AS2.45 changed over the course of fermentation. HS-SPME-GC-MS combined with non-targeted metabolomics was used to follow up and monitor the fermentation process of LPCW. In total, 43 volatile chemical substances, mostly alcohols, esters, acids, carbonyl compounds, etc., were discovered in LPCW. After 30 days of fermentation, phenylethyl alcohol had increased to 3045.83 g/mL, giving off a rose-like fresh scent. The biosynthesis of valine, leucine, and isoleucine as well as the metabolism of alanine, aspartic acid, and glutamic acid were the major routes that led to the identification of 1385 non-volatile components in total. This study offers a theoretical foundation for industrial development and advances our knowledge of the fundamental mechanism underlying flavor generation during LPCW fermentation.

Riboflavin ameliorates intestinal inflammation via immune modulation and alterations of gut microbiota homeostasis in DSS-colitis C57BL/6 mice.

While there have been advancements in understanding the direct and indirect impact of riboflavin (B2) on intestinal inflammation, the precise mechanisms are still unknown. This study focuses on evaluating the effects of riboflavin (B2) supplementation on a colitis mouse model induced with 3% dextran sodium sulphate (DSS). We administered three different doses of oral B2 (VB2L, VB2M, and VB2H) and assessed its impact on various physiological and biochemical parameters associated with colitis. Mice given any of the three doses exhibited relative improvement in the symptoms and intestinal damage. This was evidenced by the inhibition of the pro-inflammatory cytokines TNF-α, IL-1ß, and CALP, along with an increase in the anti-inflammatory cytokine IL-10. B2 supplementation also led to a restoration of oxidative homeostasis, as indicated by a decrease in myeloperoxidase (MPO) and malondialdehyde (MDA) levels and an increase in reduced glutathione (GSH) and catalase (CAT) activities. B2 intervention showed positive effects on intestinal barrier function, confirmed by increased expression of tight junction proteins (occludin and ZO-1). B2 was linked to an elevated relative abundance of Actinobacteriota, Desulfobacterota, and Verrucomicrobiota. Notably, Verrucomicrobiota showed a significant increase in the VB2H group, reaching 15.03% relative abundance. Akkermansia exhibited a negative correlation with colitis and might be linked to anti-inflammatory function. Additionally, a remarkable increase in n-butyric acid, i-butyric acid, and i-valeric acid was reported in the VB2H group. The ameliorating role of B2 in gut inflammation can be attributed to immune system modulation as well as alterations in the gut microbiota composition, along with elevated levels of fecal SCFAs.

Carbon Dot-Mediated Photodynamic Treatment Improves the Quality Attributes of Post-Harvest Goji Berries (Lycium barbarum L.) via Regulating the Antioxidant System.

Carbon dots (CDs) have been proposed as photosensitizers in photodynamic treatment (PDT), owing to their excellent biological attributes and budding fruit preservation applications. In the present study, CDs (4.66 nm) were synthesized for photodynamic treatment to improve the quality attributes in post-harvest goji berries. The prepared CDs extended the storage time of the post-harvest goji berries by 9 d. The CD-mediated PDT postponed the hardness and decay index loss, reduced the formation of malondialdehyde (MDA), hydrogen peroxide (H2O2), and superoxide anion (O2•-) significantly, and delayed the loss of vital nutrients like the total protein, phenols, and flavonoids. The CD-mediated PDT improved the catalase (CAT), ascorbate peroxidase (APX), peroxidase (POD), phenylalanine ammonia-lyase (PAL), glutathione reductase (GR), and superoxide dismutase (SOD) activities, but did not improve polyphenol oxidase (PPO) activity. In addition, The CD-mediated PDT induced the accumulation of ascorbic acid (ASA) and glutathione (GSH). Overall, a CD-mediated PDT could extend the storage time and augment the quality attributes in post-harvest fresh goji berries by regulating the antioxidant system.

Normal distribution of H3K9me3 occupancy co-mediated by histone methyltransferase BcDIM5 and histone deacetylase BcHda1 maintains stable ABA synthesis in Botrytis cinerea TB-31.

Abscisic acid (ABA) is a conserved and important "sesquiterpene signaling molecule" widely distributed in different organisms with unique biological functions. ABA coordinates reciprocity and competition between microorganisms and their hosts. In addition, ABA also regulates immune and stress responses in plants and animals. Therefore, ABA has a wide range of applications in agriculture, medicine and related fields. The plant pathogenic ascomycete B. cinerea has been extensively studied as a model strain for ABA production. Nevertheless, there is a relative dearth of research regarding the regulatory mechanism governing ABA biosynthesis in B. cinerea. Here, we discovered that H3K9 methyltransferase BcDIM5 is physically associated with the H3K14 deacetylase BcHda1. Deletion of Bcdim5 and Bchda1 in the high ABA-producing B. cinerea TB-31 led to severe impairment of ABA synthesis. The combined analysis of RNA-seq and ChIP-seq has revealed that the absence of BcDIM5 and BcHda1 has resulted in significant global deficiencies in the normal distribution and level of H3K9me3 modification. In addition, we found that the cause of the decreased ABA production in the ΔBcdim5 and ΔBchda1 mutants was due to cluster gene repression caused by the emergence of hyper-H3K9me3 in the ABA gene cluster. We concluded that the ABA gene cluster is co-regulated by BcDIM5 and BcHda1, which are essential for the normal distribution of the B. cinerea TB-31 ABA gene cluster H3K9me3. This work expands our understanding of the complex regulatory network of ABA biosynthesis and provides a theoretical basis for genetic improvement of high-yielding ABA strains.

Effects of different chemical modifications on physicochemical and antioxidation properties of Lycium barbarum seed dreg polysaccharides.

Recent studies have witnessed that chemical modification can improve the physicochemical and functional properties of plants' polysaccharides. Herein, we modified the natural Lycium barbarum seed dreg polysaccharides (LBSDPs) by sulfation (S-LBSDPs), phosphorylation (P-LBSDPs), and carboxymethylation (C-LBSDPs), and evaluated the chemical composition and antioxidant activity of their derivatives. Natural polysaccharides and their derivatives exhibited typical polysaccharide absorption peaks and characteristic group absorption peaks in FT-IR spectra along with maximum UV absorption. After modification, the total sugar and protein contents of the derivatives were decreased, whereas the uronic acid content was increased. Among the three derivatives, sulfated polysaccharides displayed excellent thermal stability. S-LBSDP and P-LBSDP showed the highest ABTS radical scavenging and reducing power while S-LBSDPs and C-LBSDPs showed better DPPH radical scavenging effect, and P-LBSDPs showed considerable Fe2+ chelating ability. Our data indicate that chemical modifications can impart a positive effect on the antioxidant potential of plant-derived polysaccharides.

Physicochemical and functional properties of carboxymethylated insoluble dietary fiber of Lycium barbarum seed dreg.

Lycium barbarum seed dregs (LBSDs) were used for carboxymethyl modification, resulting in three degree of substitution samples (DS). Based on the substitution degree, samples were designated as low degree of substitution insoluble dietary fiber (L-IDF), medium degree of substitution insoluble dietary fiber (M-IDF) and high degree of substitution insoluble dietary fiber (H-IDF). Physicochemical and functional properties of IDFs were examined in relation to carboxymethylation degree. Infrared Fourier transform spectroscopy (FT-IR) confirmed the carboxymethyl group. According to the results, IDF, L-IDF, M-IDF, and H-IDF acquired higher enthalpy changes, and their thermal stability improved significantly. A higher DS resulted in an increase in hydration properties such as water retention capacity and water swelling capacity, as well as functional properties such as glucose adsorption capacity, nitrite ion adsorption capacity, and cholesterol adsorption capacity. As a result, carboxymethylation could effectively enhance the biological properties of L. barbarum seed dreg insoluble dietary fiber (LBSDIDF).

Oxygen Isotope Analysis of Nanomole Phosphate Using PO3- Fragment in ESI-Orbitrap-MS.

The oxygen isotope composition of phosphate is a useful tool for studying biogeochemical phosphorus cycling. However, the current Ag3PO4 method is not only tedious in PO43- extraction and purification but also requires a large-sized sample at the micromole level, thereby limiting its application. Here, we present an approach to measuring the oxygen isotope composition, δ18O, of dissolved phosphate at the nanomole level using electrospray ionization Orbitrap mass spectrometry (ESI-Orbitrap-MS). We compared the reproducibility of δ18O measurements using the H2PO4- ions (m/z = 97 and 99 for H2P16O4- and H2P18O16O3-, respectively) and using the PO3- fragment ions (m/z = 79 and 81 for P16O3- and P18O16O2-, respectively) generated by source fragmentation and by higher-energy collisional dissociation, respectively. The results demonstrate that phosphate δ18O can be more reliably measured by the PO3- ions than by the H2PO4- ions. PO3- generated by source fragmentation at 40 V achieved the highest reproducibility for δ18O based on precision tests. Furthermore, the mass spectrum for a 50:50 µM mixed solution of phosphate and sulfate revealed that PO3- ions resulting from source fragmentation at 40 V are the predominant species in the Orbitrap analyzer. Notably, P16O3- ions (m/z: 79) are not interfered with by 32S16O3- (m/z: 80) ions. This is in contrast to the case for 1H2P16O4- ions, which share the same m/z value with 1H32S16O4- ions and exhibit much lower signal intensity than HSO4- ions. Using the PO3- fragment method and six phosphate standards with a wide range of δ18O values, we obtained a calibration line with a slope of 0.94 (R2 = 0.98). The overall uncertainty for ESI-Orbitrap-MS phosphate δ18O measurement was 0.8‰ (n = 30; 1 SD). With much room for improvement, the PO3- fragment method presents a better approach to measuring the phosphate oxygen isotope composition, applicable to nanomole sample sizes in a liquid phase.

Genetic, Clinical, and Pathologic Backgrounds of Children With X-Linked Alport Syndrome in China: A Monocenter Study.

Background. Characteristics of X-linked Alport syndrome (XLAS) in a cohort of Chinese children. Methods. This work is a retrospective study covering the clinical information, pathological data, and gene sequencing results of 32 cases with XLAS from 2011 to 2022. Results. Among these 32 patients, the youngest age of onset was 3 months. Renal biopsy was performed on 29 children. The lamellated glomerular basement membrane was observed in 19 children using electron microscopy (65.5%). Of the 26 samples tested, 73.1% were found to be negative for collagen-a5 under immunohistochemical staining, showing clinical significance. Next-generation sequencing (NGS) detected 27 pathogenic gene mutations. A total of 15.4% of patients carried de novo mutations. Conclusions. The boys with XLAS showed more typical pathological performance than the girls. Patients with severe mutation were more likely to have proteinuria and hearing impairment. Renal pathology combined with NSG is an important means of diagnosis of AS.

Effect of ATG8 or SAC1 deficiency on the cell proliferation and lifespan of the long-lived PMT1 deficiency yeast cells.

Autophagy is pivotal in maintaining intracellular homeostasis, which involves various biological processes, including cellular senescence and lifespan modulation. Being an important member of the protein O-mannosyltransferase (PMT) family of enzymes, Pmt1p deficiency can significantly extend the replicative lifespan (RLS) of yeast cells through an endoplasmic reticulum (ER) unfolded protein response (UPR) pathway, which is participated in protein homeostasis. Nevertheless, the mechanisms that Pmt1p regulates the lifespan of yeast cells still need to be explored. In this study, we found that the long-lived PMT1 deficiency strain (pmt1Δ) elevated the expression levels of most autophagy-related genes, the expression levels of total GFP-Atg8 fusion protein and free GFP protein compared with wild-type yeast strain (BY4742). Moreover, the long-lived pmt1Δ strain showed the greater dot-signal accumulation from GFP-Atg8 fusion protein in the vacuole lumen through a confocal microscope. However, deficiency of SAC1 or ATG8, two essential components of the autophagy process, decreased the cell proliferation ability of the long-lived pmt1Δ yeast cells, and prevented the lifespan extension. In addition, our findings demonstrated that overexpression of ATG8 had no potential effect on the RLS of the pmt1Δ yeast cells, and the maintained incubation of minimal synthetic medium lacking nitrogen (SD-N medium as starvation-induced autophagy) inhibited the cell proliferation ability of the pmt1Δ yeast cells with the culture time, and blocked the lifespan extension, especially in the SD-N medium cultured for 15 days. Our results suggest that the long-lived pmt1Δ strain enhances the basal autophagy activity, while deficiency of SAC1 or ATG8 decreases the cell proliferation ability and shortens the RLS of the long-lived pmt1Δ yeast cells. Moreover, the maintained starvation-induced autophagy impairs extension of the long-lived pmt1Δ yeast cells, and even leads to the cell death.

Highly Enantioselective Ir-Catalyzed Hydrogenation of Pyrazolo[1,5-a]pyrimidine for the Synthesis of Zanubrutinib.

A highly enantioselective catalytic reduction of pyrazolo[1,5-a]pyrimidine to zanubrutinib has been realized by the Ir/(R)-t-Bu-FcPhox complex. This chiral product could be obtained in up to >99% ee in the asymmetric transformation without any other additives, providing a new route for the asymmetric synthesis of zanubrutinib.

Comparison of efficacy between endoscope-assisted anterior cervical discectomy and fusion (ACDF) and open ACDF in the treatment of single-segment cervical spondylotic myelopathy.

BACKGROUND: In this study, we compared the clinical efficacy of endoscope-assisted anterior cervical discectomy and fusion (ACDF) with open ACDF in the treatment of single-segment cervical spondylotic myelopathy. METHODS: A retrospective analysis was performed on 52 patients with single-segment cervical spondylotic myelopathy between June 2021 and February 2022, including 33 males and 19 females, with a mean age of 58.42 ± 9.26) years. Among them, 28 patients were treated with endoscope-assisted ACDF (Group A), including 2 cases of C4/5 segment, 16 cases of C5/6 segment, and 10 cases of C6/7 segment; 24 patients were treated with open ACDF (Group B), including 4 cases of C4/5 segment, 11 cases of C5/6 segment, and 9 cases of C6/7 segment. The operation time, intraoperative blood loss, hospital stay, and complications were recorded and compared between the two groups. The Visual Analogue Scale (VAS) and the Japanese Orthopaedic Association (JOA) score were used for clinical evaluation during the follow-up in the 1st month and 3rd month after surgery, and at the final follow-up. RESULTS: The 52 patients were followed up on average for 13.04 months (12-17 months). The operation time in Group A and Group B was (105.18 + 8.66) minutes and (81.88 + 6.05) minutes, the intraoperative blood loss was (84.29 + 13.45) mL and (112.92 + 17.81) mL, and the hospital stay was (6.75 + 1.29) days and (7.63 + 1.41) days, respectively. The difference between the two groups was statistically significant (P < 0.05). The VAS and JOA scores in the 1st month and the 3rd month after surgery and the last follow-up significantly improved in both groups compared with those before surgery (P < 0.05). The VAS and JOA scores of Group A in the 1st month, 3rd month after surgery, and the last follow-up were better than those in Group B (P < 0.05). The complication rate in Group A was 7% (2/28), which was not significantly different from the 17% (4/24) in Group B (P > 0.05). CONCLUSION: Both endoscope-assisted ACDF and open ACDF can achieve satisfactory clinical efficacy in the treatment of single-segment cervical spondylotic myelopathy. Although the operation time of endoscope-assisted ACDF is prolonged, it has the advantages of clear vision, thorough decompression, less blood loss, and reduced risk of nerve damage, and is worthy of clinical promotion and application.