Time trends in the incidence of interstitial lung disease across Brazil, Russia, India, China and South Africa (BRICS) from 1990 to 2019: An age-period-cohort analysis.

BACKGROUND AND OBJECTIVE: The global incidence of interstitial lung disease (ILD) has risen over the past few decades. However, few studies have evaluated the status and incidence trends of ILD in Brazil, Russia, India, China and South Africa (BRICS). This study assesses the trends of ILD incidence across the BRICS with an emphasis on ILD changes from 1990 to 2019. METHODS: Incidence rates were estimated by the data obtained from the Global Burden of Disease Study 2019 (GBD 2019). Age-period-cohort modelling was used to estimate the effects on ILD from 1990 to 2019, and the net drift and local drift were calculated. RESULTS: In 2019, a total of 11.4 million cases of ILD were reported in the BRICS countries. From 1990 to 2019, the incidence rate of ILD in BRICS showed an upward trend. India consistently reported the highest incidence rate, while China showed the fastest growth rate (107.6%). Russia reported a similar incidence rates for men and women, with a lower age of peak incidence compared to the other four countries. We found the time effect was unfavourable for BRICS in the first decade, especially for Brazil; in China and Brazil, the risk of people born after 1960 has rapidly decreased. CONCLUSION: ILD shows a rising incidence in BRICS. with the trends varying based on age and other environmental factors. BRICS should strengthen specific public health approaches and policies for different stages and populations.

Transoral thyroidectomy vestibular approach versus non-transoral endoscopic thyroidectomy: a comprehensive systematic review and meta-analysis.

BACKGROUND: To conduct a meta-analysis to compare the short-term outcomes of transoral thyroidectomy vestibular approach (TOTVA) with non-transoral endoscopic thyroidectomy (NTET). METHODS: MEDLINE, EMBASE, science citation index expanded, and the Cochrane Central Register of Controlled Trials in the Cochrane Library from January 2007 to January 2021 were searched for relevant literature. The evaluated endpoints were intra-operative and post-operative outcomes. RESULTS: Ten eligible, non-randomized comparative studies involving 1677 patients were included. Meta-analysis results revealed that TOTVA was associated with significantly longer operative time [weighted mean differences (WMD), 22.60; 95%confidence interval (CI), 7.51-37.69; P = 0.003]. No significant differences were found between TOTVA group and NTET group in terms of post-operative outcomes. CONCLUSION: TOTVA appears to be an equally feasible and safe surgical procedure as NTET for patients with benign thyroid nodules and selected differentiated thyroid carcinomas.

SNP discovery of PRKAB1 gene and their associations with growth traits in goats.

AMPK plays an important role in regulating the metabolism of carbohydrate, lipid and protein in an organism, and is considered to be a key regulator of cellular energy homeostasis. In recent years, attention has been drawn to AMPK subunit polymorphisms and their association with economical traits of domestic animals and fowls. PRKAB1 encodes the ß1 regulatory subunit of AMPK, and it has been reported that PRKAB1 may be applied in breeding programs of meat-type chicken. To date, the polymorphism of goat PRKAB1 gene and its associations remain unknown. In this paper, the polymorphism of PRKAB1 gene was detected in 316 goats of three breeds. A total of four novel single nucleotide polymorphisms (SNPs) of PRKAB1 gene were revealed by sequence analysis. Among them, three were in the coding region (285 C > A, 297 C > A, 309 C > T), and they were all synonymous. One was in the intron (229 A > G). The associations between polymorphic loci and the growth traits of Xuhuai and Haimen goats were analyzed, and significant associations were found in body length index and trunk index (p < 0.05) for Xuhuai breed, while no significant associations in Haimen breed. Our results provide useful information for the improvement and breeding of Chinese native goats.

Fluorescent Talarolactones from Talaromyces sp.

(+)-Talarolactone C (1), Talarolactone A (2), Talarolactone B (3, sulfoxide derivative), and Talarolactone D (4, sulfone derivative) were isolated from Talaromyces sp. which was cultured in rice medium with sodium butyrate. The structures of talarolactone analogs above were characterized by a combination of spectroscopic, X-ray crystallographic, and computational methods. These talarolactones and Talarolactone A sodium (5) with the same carbon skeleton showed different fluorescence characteristics.

An epigenetic modifier induces production of 3-(4-oxopyrano)-chromen-2-ones in Aspergillus sp. AST0006, an endophytic fungus of Astragalus lentiginosus.

Incorporation of the epigenetic modifier suberoylanilide hydroxamic acid (SAHA) into a potato dextrose broth culture of the endophytic fungus Aspergillus sp. AST0006 affected its polyketide biosynthetic pathway providing two new 3-(4-oxopyrano)-chromen-2-ones, aspyranochromenones A (1) and B (2), and the isocoumarin, (-)-6,7-dihydroxymellein (3). Eight additional metabolites (4-11) and two biotransformation products of SAHA (12-13) were also encountered. The planar structures and relative configurations of the new metabolites 1-2 were elucidated with the help of high-resolution mass, 1D and 2D NMR spectroscopic data and the absolute configurations of 1-3 were determined by comparison of experimental and calculated ECD data. Possible biosynthetic pathways to 1 and 2 are presented.

Recombinant streptavidin fusion proteins as signal reporters in rapid test of human hepatitis C virus infection.

BACKGROUND: Early diagnosis of hepatitis C virus (HCV) infection is very important for the treatment of the disease. Development of sensitive and specific rapid detection assays is of great significance for the diagnosis. Here, we describe a promising method of using gold-labeled streptavidin fusion proteins as novel signal reporter in a rapid detection assay for HCV infection. METHODS: Recombinant genes encoding streptavidin fused with Escherichia coli maltose-binding protein (MBP) or with a portion of bacterial translational initiation factor 2 were cloned in expression vectors pMAL-5CX and pET28 and transformed in proper Escherichia coli host strains. The genes were induced and streptavidin fusion proteins, named M-STV and IF-STV, respectively, were purified by affinity chromatography to over 90% purity. The biotin-binding activity of M-STV and IF-STV was tested by enzyme-linked immunosorbent assay (ELISA). M-STV was labeled with colloidal gold nanoparticles and used as a signal reporter to develop a lateral flow-based rapid test for detecting anti-HCV antibodies in human blood samples. RESULTS: M-STV showed slightly higher biotin-binding activity and similar binding specificity as compared to commercial streptavidin. The gold-labeled M-STV bound specifically to biotin moieties immobilized on the rapid test strips in a dose-responsive manner and was successfully used in detecting HCV antibodies in serum samples of patients infected with HCV. The rapid test displayed higher detection sensitivity than gold-labeled commercial NeutrAvidin. CONCLUSION: Our results indicate that gold-labeled M-STV is a promising agent in rapid tests of HCV infection and possibly other viral infections.

Synthesis of fluorinated carbazoles via C-H arylation catalyzed by Pd/Cu bimetal system and their antibacterial activities.

An effective intramolecular C-H arylation reaction catalyzed by a bimetallic catalytic system Pd(OAc)2/CuI for the synthesis of fluorine-substituted carbazoles from corresponding N-phenyl-2-haloaniline derivatives under ligand free conditions is demonstrated. The established method is effective for both N-phenyl-2-bromoaniline and N-phenyl-2-chloroaniline, and requires the low loading of Pd(OAc)2 (0.5 mol%). A series of new fluorinated carbazoles were synthesized in excellent yields using the protocol (>83%, 19 examples) and were fully characterized by (1)H, (13)C and (19)F NMR spectral data, HRMS and elemental analysis. All compounds were evaluated for their antibacterial activities against four bacteria (Bacillus subtilis, Staphylococcus aureus, Escherichia coli and methicillin-resistant S. aureus with resistance to gentamicin) by serial dilution technique. All tested compounds showed antibacterial activity against three test strains (S. aureus, B. subtilis and MRSA), and most of these compounds displayed pronounced antimicrobial activities against these three strains with low MIC values ranging from 0.39 to 6.25 µg/mL. Among them, compounds 7 and 14 exhibited potent inhibitory activity better than reference drugs meropenem and streptomycin. Three compounds (2, 4 and 5) showed antibacterial activity against E. coli. with MIC values from 12.5 to 25 µg/mL.

Diversity of endophytic fungi associated with the foliar tissue of a hemi-parasitic plant Macrosolen cochinchinensis.

Foliar fungal endophytes are an important plant-associated fungal group. However, little is known about these fungi in hemi-parasitic plants, a unique plant group which derive nutrients from living plants of its hosts by haustoria while are photosynthetic to some degree. In this paper, the endophytic fungi in the leaves of a species of hemi-parasitic plant, Macrosolen cochinchinensis, were studied by both culture-dependent and culture-independent methods. By culture-dependent method, a total of 511 isolates were recovered from 452 of 600 leaf fragments (colonization rate = 75.3 %) and were identified to be 51 taxa. Valsa sp. was the most abundant (relative abundance = 38.4 %), followed by Cladosporium sp. 1 (13.5 %), Ulocladium sp. (4.3 %), Phomopsis sp. 2 (3.7 %), Hendersonia sp. (3.5 %), and Diaporthe sp. 4 (3.5 %). The Shannon index (H') of the isolated endophytic fungi was 2.628, indicating a moderate diversity. By culture-independent method, Aspergillus spp., Cladosporium sp., Mycosphaerella sp., Acremonium strictum, and Tremella sp. were detected. To our knowledge, the Tremella species have never been detected as endophytes so far. In addition, a cloned sequence was not similar with any current sequence in the Genbank, which may represent a novel species. Altogether, this study documented endophytic fungal assemble in the leaves of M. cochinchinensis which was worthy of our attention, and may expand our knowledge about endophytic fungi within the photosynthetic tissues of plants.

Association between nighttime sleep duration and quality with knee osteoarthritis in middle-aged and older Chinese: A longitudinal cohort study.

BACKGROUND: The association between nighttime sleep duration and sleep quality with the risk of knee osteoarthritis (OA) remains unclear. This study aimed to examine the longitudinal association among middle-aged and older adults in China. METHODS: The data used in this study were obtained from the China Health and Retirement Longitudinal Study (CHARLS) surveys conducted in 2011 and 2015. Nighttime sleep duration was categorized into five groups: <6 h, 6 to <7 h, 7 to <8 h, 8 to <9 h, and ≥9 h/night. Sleep quality was assessed by restless days in the past week (<1, 1-2, 3-4, and 5-7 days/week). Multivariate logistic regression models were used to assess the association between sleep duration and quality with incident knee OA. RESULTS: A total of 11,114 participants who did not have knee OA at baseline were enrolled in this study. After 4 years of follow-up, the overall incidence of knee OA was 8.07 %. Compared to 7 to <8 h of sleep duration, short sleep duration (<6 h/night) was associated with a significantly increased risk of incident knee OA in the fully adjusted model [odds ratio (OR) =1.73, 95 % confidence interval (CI): 1.33-2.25]. Additionally, participants with 5-7 sleep restless days/week were associated with significantly increased risk of incident knee OA (OR = 1.88, 95 % CI: 1.48-2.38). CONCLUSIONS: Short nighttime sleep duration and poor sleep quality are associated with increased risk of incident knee OA.

The Negative Impacts of Sarcopenia on Primary Total Knee Arthroplasty under the Enhanced Recovery after Surgery Protocol.

OBJECTIVE: Sarcopenia, as an emerging public health concern, has been associated with postoperative adverse outcomes in various surgical procedures. However, the evidence regarding the impacts of sarcopenia on total knee arthroplasty (TKA) remained limited. This study aimed to assess the impacts of sarcopenia on primary TKA based on the enhanced recovery after surgery (ERAS) protocol. METHODS: This retrospective study included 291 patients who received unilateral TKA from October 2017 to May 2018 in our institution. Sarcopenia was diagnosed based on the algorithm of Asian Working Group for Sarcopenia 2019. The handgrip strength was measured using a handheld dynamometer and the muscle mass was estimated by a previously validated anthropometric equation. Patients were classified into sarcopenia group and non-sarcopenia group. The outcomes included complications, postoperative length of stay (LOS), total hospitalization cost, operative time, total estimated blood loss, blood transfusion rate, and the 12-item forgotten joint score (FJS-12) at the follow-up. The propensity score matching (PSM) was used to adjust confounding factors. We compared continuous variables using Student's t-test and the Wilcoxon Mann-Whitney U test for normal and non-normal distributions, respectively, and categorical variables with chi-square tests. RESULTS: Of the 291 patients, 58 (19.9%) patients were identified as having sarcopenia. After PSM, each group matched 42 patients. All matched patients were followed-up at least 5 years. Patients with sarcopenia had higher rates of surgical complications compared to the non-sarcopenia group (p = 0.019), and no significant difference was observed in 30-day readmission, and periprosthetic joint infection. The sarcopenia group had significantly longer LOS (p = 0.038), higher total hospitalization (p = 0.015) than the non-sarcopenia group. For the FJS-12 scores at follow-up, patients with sarcopenia had significantly higher scores than the non-sarcopenia group (p = 0.024). CONCLUSION: Our findings indicated sarcopenia may be a risk factor for postoperative complications, prolonged LOS, increased hospitalization cost and reduced patient satisfaction.

Estimating the global prevalence of secondary hyperparathyroidism in patients with chronic kidney disease.

Background: Chronic kidney disease (CKD)-related secondary hyperparathyroidism (SHPT) is associated with higher morbidity and death. The goal of this study was to mine the SHPT data already available to do a meta-analysis on the global prevalence of SHPT caused by CKD. Methods: Embase, Medline, Web of Science, Cochrane Central Databases, and Google Scholar were searched to identify studies on the prevalence of SHPT due to CKD from inception to November 2023. Pooled prevalence was calculated using the DerSimonian-Laird random effects model with a logit transformation. Results: Twenty-one eligible studies involving 110977 patients were included. Our results revealed that the estimated global prevalence of SHPT due to CKD was 49.5% (95% CI 30.20-68.18), regardless of the diagnostic criteria. For subgroup analysis, Southern Asia (84.36%, 95% CI 79.35-88.34) had a significantly higher SHPT prevalence than other geographic regions. SHPT due to CKD was most prevalent in China (85.14%, 95% CI 81.74-88.00). Conclusions: SHPT due to CKD is highly prevalent. This necessitates awareness and therapeutic approaches from primary care physicians, medical professionals, and health strategy authorities. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024514007.

Exploring Causal Relationships between Leukocyte Telomere Length, Sex Hormone-Binding Globulin Levels, and Osteoporosis Using Univariable and Multivariable Mendelian Randomization.

OBJECTIVE: Recent evidence supports that leukocyte telomere length (LTL) may be positively associated with healthy living and inversely correlated with the risk of age-related diseases, including osteoporosis. Furthermore, it is important to note that sex hormone-binding globulin (SHBG) levels play a crucial role in the regulation of osteoporosis by influencing the availability of sex hormones. Hence, this study holds significant importance as it aims to unravel the roles of LTL and SHBG levels and determine which one acts as a predominant intermediary factor in influencing osteoporosis. Using Mendelian randomization (MR), we can gain valuable insights into the intricate relationships between aging, sex hormones, and bone health. METHODS: Univariable and multivariable and MR analyses were employed in this study. First, we used genetic variants associated with both LTL, as determined from a study involving 472,174 European participants by Codd et al., and SHBG levels, as identified in a study conducted by Ruth et al. with 370,125 participants, as instrumental variables (IVs). Then we aimed to establish a causal relationship between LTL and SHBG levels and their potential impact on osteoporosis using univariable MR. Finally, we conducted multivariable MR to provide insights into the independent and combined effects of LTL, SHBG levels on osteoporosis risk. We used various MR methods, with the primary analysis employing the inverse-variance weighted (IVW) model. RESULTS: Univariable MR analysis reveals a potential causal effect of longer LTL on reduced risk of osteoporosis [odds ratio (OR): 0.85; 95% confidence interval (CI): 0.73-0.99; p = 0.03]. Conversely, higher genetically determined SHBG levels affect the risk of osteoporosis positively. (OR: 1.38; 95% CI: 1.09-1.75; p < 0.01). We observed a negative causal effect for LTL on the occurrence of SHBG (OR: 0.96; 95% CI 0.94-0.98, p < 0.01). After adjustment of using multivariable MR, the causal effect of LTL on osteoporosis (OR: 0.92; 95% CI: 0.84-1.03; p = 0.14), and the effect of SHBG on osteoporosis (OR: 1.43; 95% CI: 1.16-1.75; p < 0.01) were observed. CONCLUSION: Longer LTL may confer a protective effect against osteoporosis. Additionally, the levels of SHBG appear to play a crucial role in mediating the relationship between LTL and osteoporosis. By understanding the interplay between these factors, we can gain valuable insights into the mechanisms underlying bone health and aging and potentially identify new avenues for prevention and intervention strategies.

Association between handgrip strength weakness and asymmetry with incident hip fracture among older Chinese adults.

BACKGROUND: To evaluate the association between handgrip strength (HGS) weakness and asymmetry with incident hip fracture among older Chinese adults. METHODS: Data was obtained from the 2011 and 2015 waves of the China Health and Retirement Longitudinal Study (CHARLS). HGS weakness was defined as maximal HGS 〈 28 kg in men and < 18 kg in women. HGS asymmetry was defined as the HGS ratio < 0.9 or 〉 1.1. Participants were categorized into normal HGS, weakness only, asymmetry only, and both weakness and asymmetry. Given the sex differences in HGS, the association between HGS weakness and asymmetry was analyzed by sex using the multivariable logistic regression models. RESULTS: A total of 4789 participants aged ≥ 60 years old without hip fracture at baseline were included in the final analysis. Over the four-year follow-up, there were 152 (3.17 %) participants having incident hip fractures, of which 69 (2.90 %) were men and 83 (3.45 %) were women. Compared to the normal group, men with both weakness and asymmetry had a significantly higher risk of incident hip fracture in the fully adjusted model (adjusted odds ratio (OR): 2.31, 95 % confidence interval (CI):1.17-4.52). There was no significant association between HGS asymmetry and weakness with hip fracture in women. CONCLUSIONS: Our findings indicated that among the Chinese population, men with both HGS weakness and asymmetry were associated with increased odds of hip fracture, while no significant association was observed in women.

Longitudinal Association between Uric Acid and Incident Sarcopenia.

BACKGROUND: Sarcopenia has emerged as a significant public health concern. Uric acid (UA), as a metabolite with excellent antioxidant capacity, has been found to be associated with sarcopenia. However, the casual effects of UA on incident sarcopenia still remain unclear. Our study aimed to explore the longitudinal association between UA and incident sarcopenia among middle-aged and older adults. METHOD: A total of 5086 participants aged ≥45 years old without sarcopenia at baseline were included from the China Health and Retirement Longitudinal Study (CHARLS). Due to the sex differences, the UA levels were analyzed by categorizing into sex-specific quartiles or by using UA levels as a continuous variable (per 1 mg/dL). The longitudinal association between UA and incident sarcopenia was evaluated using Cox proportional hazards regression models. RESULTS: During the 4-year follow-up period, 552 (10.85%) participants with incident sarcopenia were identified, of which 370 cases were males and 182 cases were females. Compared to the first quartile (Q1) UA levels, the Q3 and Q4 UA levels were significantly associated with lower risk of incident sarcopenia in males (Q3: adjusted hazard ratio (HR), 0.72; 95% CI (confidence interval), 0.54-0.97; Q4: HR, 0.57; 95% CI, 0.41-0.80). When UA was as a continuous variable (per 1 mg/dL), the association in males remained significant (HR: 0.87; 95% CI: 0.79-0.97). No significant association was observed in females. CONCLUSION: Our findings indicated that UA was negatively associated with incident sarcopenia in males but not in females among middle-aged and older Chinese.

Transoral thyroidectomy vestibular approach vs. conventional open thyroidectomy: a systematic review and meta-analysis.

The purpose of this study was to compare the intraoperative outcomes and postoperative complications of patients experiencing transoral thyroidectomy vestibular approach (TOTVA) and conventional open thyroidectomy (COT). PUBMED, EMBASE, the Cochrane Central Register of Controlled Trials in the Cochrane Library, and Web of science expanded between January 2007 and November 2022 comparing TOTVA and COT was exhaustively searched. Fifteen non-randomized controlled studies involving 2955 patients were included. The results of meta-analyses indicated that TOTVA was associated with longer operative time (WMD, 66.86; 95%CI, 47.15-86.56; P < 0.00001), more blood loss (WMD, 2.83; 95%CI, 1.77-3.90; P < 0.00001), higher incidence of wound infection (OR, 5.62; 95%CI, 1.57-20.10, P = 0.008). There was no significant difference in terms of transient recurrent laryngeal nerve (RLN) palsy and other postoperative outcomes. In conclusion, TOTVA appears to be a feasible and safe approach for the treatment of patients with benign thyroid nodules and selected differential thyroid carcinomas just like the COT.

Protective effects of combined treatment with ciprofol and mild therapeutic hypothermia during cerebral ischemia-reperfusion injury.

Despite improvement in cardiopulmonary resuscitation (CPR) performance, cardiac arrest (CA) is still associated with poor prognosis. The high mortality rate is due to multi-organ dysfunction caused by cerebral ischemia and reperfusion injury (I/R). The guidelines for CPR suggest the use of therapeutic hypothermia (TH) as an effective treatment to decrease mortality and the only approach confirmed to reduce I/R injury. During TH, sedative agents (propofol) and analgesia agents (fentanyl) are commonly used to prevent shiver and pain. However, propofol has been associated with a number of serious adverse effects such as metabolic acidosis, cardiac asystole, myocardial failure, and death. In addition, mild TH alters the pharmacokinetics of agents (propofol and fentanyl) and reduces their systemic clearance. For CA patients undergoing TH, propofol can be overdosed, leading to delayed awakening, prolonged mechanical ventilation, and other subsequent complications. Ciprofol (HSK3486) is a novel anesthetic agent that is convenient and easy to administer intravenously outside the operating room. Ciprofol is rapidly metabolized and accumulates at low concentrations after continuous infusion in a stable circulatory system compared to propofol. Therefore, we hypothesized that treatment with HSK3486 and mild TH after CA could protect the brain and other organs.

Regional versus general anesthesia in older patients for hip fracture surgery: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The optimal anesthesia technique for older patients undergoing hip fracture surgery remains controversial. We performed a systematic review and meta-analysis of updated randomized controlled trials (RCTs) to assess whether regional anesthesia was superior to general anesthesia in hip fracture surgery. METHODS: We searched PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials from January 2000 until April 2022. RCTs directly comparing regional and general anesthesia in hip fracture surgery were included in the analysis. The incidence of delirium and mortality were the primary outcomes and other perioperative outcomes including complications were secondary outcomes. RESULTS: Thirteen studies involving 3736 patients were included in this study. There was no significant difference in the incidence of delirium (odds ratio [OR] 1.09; 95% confidence interval [CI] 0.86, 1.37) and mortality (OR 1.08; 95% CI 0.71, 1.64) between the two groups. Patients receiving regional anesthesia in hip fracture surgery were associated with a reduction in operative time (weighted mean difference [WMD]: - 4.74; 95% CI - 8.85, - 0.63), intraoperative blood loss (WMD: - 0.25; 95% CI - 0.37, - 0.12), postoperative pain score (WMD: - 1.77; 95% CI - 2.79, - 0.74), length of stay (WMD: - 0.10; 95% CI - 0.18, - 0.02), and risk of acute kidney injury (AKI) (OR 0.56; 95% CI 0.36, 0.87). No significant difference was observed in the other perioperative outcomes. CONCLUSIONS: For older patients undergoing hip fracture surgery, RA did not significantly reduce the incidence of postoperative delirium and mortality compared to GA. Due to the limitations of this study, the evidence on delirium and mortality was still inconclusive and further high-quality studies are needed.

Soluble thrombomodulin alleviates Diquat-induced acute kidney injury by inhibiting the HMGB1/IκBα/NF-κB signalling pathway.

Our research aimed to investigate whether soluble thrombomodulin (sTM) relieved Diquat (DQ)-induced acute kidney injury (AKI) via HMGB1/IκBα/NF-κB signaling pathways. An AKI rat model was constructed using DQ. Pathological changes in renal tissue were detected by HE and Masson staining. Gene expression was determined using qRT-PCR, IHC, and western blotting. Cell activity and apoptosis were analysed using CCK-8 and Flow cytometry, respectively. An abnormal kidney structure was observed in DQ rats. The levels of blood urea nitrogen (BUN), creatinine (CRE), uric acid (UA), oxidative stress, and inflammatory responses in the DQ group increased on the 7th day but decreased on the 14th day, compared with the control group. Additionally, HMGB1, sTM, and NF-kappaB (NF-κB) expression had increased in the DQ group compared with the control group, while the IκKα and IκB-α levels had decreased. In addition, sTM relieved the damaging effects of diquat on renal tubular epithelial cell viability, apoptosis, and the inflammatory response. The levels of HMGB1, TM, and NF-κB mRNA and protein were significantly decreased in the DQ + sTM group compared with the DQ group. These findings indicated that sTM could relieve Diquat-induced AKI through HMGB1/IκBα/NF-κB signaling pathways, which provides a treatment strategy for Diquat-induced AKI.

Synthesis and Antibacterial Activity of Spiro[4H-pyran-3,3'-oxindoles] Catalyzed by Tröger's Base Derivative.

OBJECTIVE: Two classes of spiro[4H-pyran-3,3'-oxindole] derivatives were prepared via the one pot reaction of chain diketones (1-phenyl-1,3-butanedione or dibenzoyl methane), substituted isatins and malononitrile successfully catalyzed by a Tröger's base derivative 1b (5,12-dimethyl-3,10-diphenyl-bis-1H-pyrazol[b,f][4,5]-1,5-diazadicyclo[3.3.1]-2,6-octadiene). The antibacterial activity of products against three wild-type bacteria (B. subtilis, S. aureus, and E. coli) and two resistant strains (Methicillin-resistant S. aureus (18H8) and E. coli carrying the BlaNDM-1 gene (18H5)) was evaluated using the minimum inhibitory concentration (MIC).. METHODS: 1-Phenyl-1,3-butanedione 2 or dibenzoylmethane 2' (0.42 mmol), substituted isatin 3 (0.4 mmol), malononitrile 4 (0.8 mmol), Tröger's base derivative 1b (0.08 mmol), and 10 mL of acetonitrile were added to a 50 mL round bottom flask and refluxed. After the completion (TLC monitoring), water (10 mL) was added to the reaction mixture; pH = 7 was adjusted with saturated NaHCO3 (aq.), and the mixture was extracted with CH2Cl2 (50 mL × 3). Organic layers were combined and dried with anhydrous Na2SO4; the solvent was removed under vacuum, and the residue was purified by column chromatography (VDCM: VMeOH = 80: 1) to afford product 5. The antibacterial activity was tested by the MTT method. RESULTS: Seventeen spiro[4H-pyran-3,3'-oxindole] derivatives were synthesized through the reaction of chain diketones (1-phenyl-1,3-butanedione or dibenzoyl methane), substituted isatins, and malononitrile in one-pot in medium to high yields. Four compounds showed antibacterial activity, and two of them showed the same activity as the positive control Ceftazidime on S. aureus (MIC = 12.5 µg/mL). CONCLUSION: Two classes of spiro[4H-pyran-3,3'-oxindole] derivatives were prepared, and their antibacterial activity was evaluated. Tröger's base derivative 1b (5,12-dimethyl-3,10-diphenyl-bis-1H-pyrazol[b,f][4,5]- 1,5-diazadicyclo[3,3,1]-2,6-octadiene) was used as an efficient organocatalyst for the reaction of low reactive chain diketones (1-phenyl-1,3-butanedione or dibenzoyl methane), substituted isatins, and malononitrile in one-pot successfully and effectively by providing multiple active sites and alkaline environment. By the theoretical calculation, we explained the possible reaction sequence and mechanism. Due to the superiority and high efficiency of the TB framework as an organocatalyst, the reaction showed many advantages, including mild reaction conditions, low catalyst loading, and a wide substrate range. It expanded the application of Tröger's base to the multicomponent reaction in organocatalysis. Some products were screened due to their high antibacterial activity in vitro, showing their potential in new antibacterial drug development.

[The role of chondrocyte mitochondrial biogenesis in the pathogenesis of osteoarthritis].

OBJECTIVE: To summarize the role of chondrocytes mitochondrial biogenesis in the pathogenesis of osteoarthritis (OA), and analyze the applications in the treatment of OA. METHODS: A review of recent literature was conducted to summarize the changes in mitochondrial biogenesis in the course of OA, the role of major signaling molecules in OA chondrocytes, and the prospects for OA therapeutic applications. RESULTS: Recent studies reveales that mitochondria are significant energy metabolic centers in chondrocytes and its dysfunction has been considered as an essential mechanism in the pathogenesis of OA. Mitochondrial biogenesis is one of the key processes maintaining the normal quantity and function of mitochondria, and peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) is the central regulator of this process. A regulatory network of mitochondrial biogenesis with PGC-1α as the center, adenosine monophosphate-activated protein kinase, sirtuin1/3, and cyclic adenosine monophosphate response element-binding protein as the main upstream regulatory molecules, and nuclear respiratory factor 1, estrogen-related receptor α, and nuclear respiratory factor 2 as the main downstream regulatory molecules has been reported. However, the role of mitochondrial biogenesis in OA chondrocytes still needs further validation and in-depth exploration. It has been demonstrated that substances such as puerarin and omentin-1 can retard the development of OA by activating the damaged mitochondrial biogenesis in OA chondrocytes, which proves the potential to be used in the treatment OA. CONCLUSION: Mitochondrial biogenesis in chondrocytes plays an important role in the pathogenesis of OA, and further exploring the related mechanisms is of great clinical significance.