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Li-Li Xia,1,* Su-Fen Li,2,* Kan Shao,1 Xin Zhang,3 Shan Huang1 1Department of Endocrinology, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Neurology, Huai’an Second People’s Hospital and The Affiliated Huai’an Hospital of Xuzhou Medical University, Huai’an, People’s Republic of China; 3Department of Radiology, The Fourth People’s Hospital of Huai’an, Huai’an, People’s Republic of China *These authors contributed equally to this work Abstract: To investigate the correlation between computed tomography (CT) features and glycosylated hemoglobin (HbAlc) levels in patients with type 2 diabetes mellitus (T2DM) complicated with primary pulmonary tuberculosis (PTB). One hundred and eighty untreated PTB patients complicated with T2DM were selected. Based on the HbAlc level, the patients were divided into three groups: HbAlc level 9% (Group III: 100 patients). The changes of CT manifestations and HbAlc were analyzed after TB and T2DM treatment. In the three groups, the detection rate of large segmented leafy shadow was 50%, 56.2%, and 87%; the air bronchogram sign detection rate was 40.6%, 47.9%, and 77%; the discovery rate of mouth-eaten cavity was 31.2%, 45.8%, and 65%; thick wall cavity detection rate was 25%, 31.2%, and 52%; the rate of multiple cavities was 34.3%, 50%, and 73%; and bronchial TB was found in 33.3%, 21.8%, and 46%, respectively. The detection rates of lesions in Group III were significantly higher than in Group II and Group I (p

Sheng-fa Li,1,2,* Jia-jun Tang,1,2,* Jian Chen,1–3,* Pei Zhang,4,* Ting Wang,5 Tian-yu Chen,1,2 Bo Yan,1,2 Bin Huang,1,2 Liang Wang,1,2 Min-jun Huang,1,2 Zhong-min Zhang,1,2 Da-di Jin1,21Academy of Orthopedics of Guangdong Province, Guangzhou, People’s Republic of China; 2Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 3Three Gorges Central Hospital of Chongqing, Chongqing, People’s Republic of China; 4School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 5Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workAbstract: Osteoporosis is a systemic skeletal disease that is characterized by low bone density and microarchitectural deterioration of bone tissue. The increasing prevalence of osteoporosis has attracted much attention. In this study, MC3T3-E1 pre-osteoblasts were treated with the natural compound, baicalein (0.1 µmol/L, 1 µmol/L, 10 µmol/L), to stimulate differentiation over a 14-day period. In addition, a canonical ovariectomized (OVX) mouse model was used to investigate the effect of 3-month baicalein treatment (10 mg/kg per day) in preventing postmenopausal osteoporosis. In vitro, we found that baicalein induced activation of alkaline phosphatase, stimulated the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, and induced expression of osteoblast differentiation markers, ie, osteocalcin, osterix, collagen Iα1, and runt-related transcription factor 2 (RUNX2), in osteoblasts. In vivo, several bone parameters, including trabecular thickness, trabecular bone mineral density, and trabecular number, in the distal femoral metaphysis were significantly increased in OVX mice treated intragastrically with baicalein for 3 months compared with OVX mice that were not treated with baicalein. We also found that expression of osteocalcin and RUNX2 was decreased in primary ossified tissue from the OVX group, and baicalein increased the levels of osteocalcin and RUNX2 in OVX mice. These data suggest that baicalein can stimulate MC3T3-E1 cells to differentiate into osteoblasts via activation of the mTORC1 signaling pathway, which includes protein kinases and transcription factors such as P-4E/BP1 and P-S6K1.Keywords: osteoblast, osteoporosis, menopause, mTOR

The Daya Bay reactor antineutrino experiment is designed to make a precision measurement of the neutrino mixing angle θ13, and recently made the definitive discovery of its non-zero value. It utilizes a set of eight, functionally identical antineutrino detectors to measure the reactor flux and spectrum at baselines of ∼ 300-2000 m from the Daya Bay and Ling Ao Nuclear Power Plants. The Daya Bay antineutrino detectors were built in an above-ground facility and deployed side-by-side at three underground experimental sites near and far from the nuclear reactors. This configuration allows the experiment to make a precision measurement of reactor antineutrino disappearance over km-long baselines and reduces relative systematic uncertainties between detectors and nuclear reactors. This paper describes the assembly and installation of the Daya Bay antineutrino detectors. © 2013 IOP Publishing Ltd and Sissa Medialab srl.

OBJECTIVE: Physicians often administer intravenous multivitamins to intoxicated patients in the emergency department (ED); however, this practice is not supported by evidence from any prior study. We determined the prevalences of vitamin deficiencies in patients presenting to our ED with alcohol intoxication. METHODS: This study was a prospective, cross-section, observational study of a convenience sample of ED patients presenting with acute alcohol intoxication. Patients were tested for B(12), folate, and thiamine levels as add-ons to their blood samples. RESULTS: Seventy-seven patients were included in the final analysis. The mean age was 46 years, and 19% were female; the mean blood alcohol level was 280 mg/dL. Of 75 patients, no one (0%) had low B(12) or folate levels (95% confidence interval, 0-0.05); 6 (15%) of 39 patients had low thiamine levels (95% confidence interval, 0.06-0.31). Of these 6 patients, none exhibited clinical signs of thiamine deficiency. CONCLUSIONS: In our ED, patients with acute ethanol intoxication do not have B(12) or folate deficiencies. A significant minority (15%) of patients have thiamine deficiency; its clinical significance is unclear. Widespread administration of multivitamins is unwarranted by these findings, but thiamine may be considered. © 2008 Elsevier Inc. All rights reserved. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Cardiac troponin I (cTnI) is considered the most specific marker of cardiac muscle injury. We encountered several patients with rhabdomyolysis and elevated cTnI, although they did not otherwise have evidence of cardiac injury. We determined the prevalence of false-positive cTnI in emergency department (ED) patients with rhabdomyolysis. METHODS: We conducted a retrospective cohort study of ED patients admitted with a diagnosis of rhabdomyolysis. Patients were included in the study if they had a serum creatine kinase (CK) of 1000 U/L or greater and at least one serum cTnI determination. Patients with positive cTnI were considered true positives if they had either electrocardiography (EKG) or echocardiography abnormalities; false positives if both the EKG and the echocardiography were considered normal; or indeterminate if they did not have both an EKG and an echocardiogram. The primary outcome of the study was the prevalence of false-positive cTnI. Secondary outcomes included risk stratification by cocaine use, myoglobinuria, and renal failure and correlation of peak CK and troponin levels. RESULTS: One hundred nine patients were included in the final analysis; 55 (50%) patients had a positive cTnI. Of the 55 patients with positive cTnI, 32 (58%) were true positives, 18 (33%) were false positives, and 5 (9%) were indeterminate. The prevalence of false-positive cTnI was 17% (18/109, 95% confidence interval 0.10-0.25). There was no association between false-positive cTnI and cocaine use, renal failure, or myoglobinuria. There was poor correlation between peak CK and peak cTnI levels (r = -.08, 95% confidence interval -0.34 to 0.19). CONCLUSION: The prevalence of false-positive cTnI in ED patients with rhabdomyolysis is 17%. Copyright © 2005 by Elsevier Inc. [ABSTRACT FROM AUTHOR]

Background: A common complication of hemodialysis is bleeding from the dialysis site.Discussion: To demonstrate the use of 2-octyl-cyanoacrylate in controlling venous bleeding associated with hemodialysis access.Conclusion: 2-octyl-cyanoacrylate is effective in stopping venous bleeding from hemodialysis sites. [ABSTRACT FROM AUTHOR]

Ethnopharmacological Relevance: Cornus officinalis is a conventional Chinese medicine for tonifying liver and kidney in ancient China. The active ingredients from Cornus officinalis can delay the progression of cerebral aneurysms, alleviate experimental autoimmune encephalomyelitis, and show a good intervention effect on brain diseases. Loganin, the active ingredient of Cornus officinalis, has a neuroprotective effect on cerebral ischemia-reperfusion injury in mice. It is yet unknown, nevertheless, how Cornus officinalis works to treat ischemic stroke., Aim of the Study: Based on ultra-high performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UHPLC-Q-TOF-MS), network pharmacology and molecular docking, Cornus officinalis's mechanism of intervention in ischemic stroke is explored and verified by experiments., Materials and Methods: To examine the chemical components of Cornus officinalis, UHPLC-Q-TOF-MS was used. The network pharmacology was used to construct the "active ingredient-core target-main pathway" network of Cornus officinalis. Then, the link between the main active components and the key protein targets, as determined by network pharmacology, was verified through the application of molecular docking. The middle cerebral artery occlusion/reperfusion (MCAO/R) rat model used in this study was created using the suture technique. The pharmacological effects of Cornus officinalis were explored by neurological function score, behavior, TTC staining, ultrasound and flow cytometry. Western blot and qPCR were used to confirm the core target., Results: The outcomes of the investigation demonstrated that Cornus officinalis had a potent anti-ischemic stroke effect. UHPLC-Q-TOF-MS method was used to determine 24 chemical constituents in Cornus officinalis, of which 22 components had a close relationship with protein targets relevant to ischemic stroke. The 27 protein targets screened by "active ingredient-core target-main pathway" may be the possible targets of Cornus officinalis in the therapy of ischemic stroke. Most of the 27 protein targets had to do with the inflammatory response, apoptosis and energy metabolism. KEGG enrichment analysis showed that AGE/RAGE ranked high and was closely related to inflammatory response. Molecular docking predicted that the top 10 components in the network diagram had good binding with inflammatory factors IL6, IL-1β and TNF-α protein targets. Western blot research outcomes stated that Cornus officinalis could firmly impede the production of AGE, RAGE, and P-NFκB P65. Cornus officinalis had the potential to prevent ischemic stroke by drastically inhibiting the production of TNF-α, IL-1β, and IL-6, according to the results of qPCR study., Conclusion: This study found that Cornus officinalis can improve the brain injury, motor ability and blood flow velocity of MCAO/R rats and suppress the inflammatory reaction through the AGE/RAGE/NFκB pathway to exert the therapeutic effect on ischemic stroke., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Substrate access tunnel engineering is a useful strategy for enzyme modification. In this study, we improved the catalytic performance of Fe-type Nitrile hydratase (Fe-type NHase) from Pseudomonas fluorescens ZJUT001 (PfNHase) by mutating residue Q86 at the entrance of the substrate access tunnel. The catalytic activity of the mutant PfNHase-αQ86W towards benzonitrile, 2-cyanopyridine, 3-cyanopyridine, and 4-hydroxybenzonitrile was enhanced by 9.35-, 3.30-, 6.55-, and 2.71-fold, respectively, compared to that of the wild-type PfNHase (PfNHase-WT). In addition, the mutant PfNHase-αQ86W showed a catalytic efficiency (k cat /K m ) towards benzonitrile 17.32-fold higher than the PfNHase-WT. Interestingly, the substrate preference of PfNHase-αQ86W shifted from aliphatic nitriles to aromatic nitrile substrates. Our analysis delved into the structural changes that led to this altered substrate preference, highlighting an expanded entrance tunnel region, theenlarged substrate-binding pocket, and the increased hydrophobic interactions between the substrate and enzyme. Molecular dynamic simulations and dynamic cross-correlation Matrix (DCCM) further supported these findings, providing a comprehensive explanation for the enhanced catalytic activity towards aromatic nitrile substrates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: To evaluate the effect of multidisciplinary treatment (MDT) on the survival outcomes of Chinese lung cancer patients., Methods: Data from a Chinese tertiary cancer hospital of lung cancer patients were collected and divided into two groups (MDT+/-) according to whether the patients had received an MDT. The survival analysis was performed after propensity score matching (PSM)., Results: Before PSM, more patients in the MDT+ group had documented information on clinical characteristics and showed more unfavorable clinical characteristics than patients in the MDT- group. After PSM, there was no imbalance in the first-line treatment strategies between the two groups. When the patients were analyzed separately, for patients in the MDT- group, age at diagnosis, Eastern Cooperative Oncology Group (ECOG) score, stage, smoking history, and epidermal growth factor receptor (EGFR) gene status were all significant factors for survival (p < 0.05). For patients in the MDT+ group, only age at diagnosis, stage, and comorbidities were significant factors for survival (p < 0.05). Moreover, age at diagnosis, ECOG score, stage, EGFR gene status, and MDT were all significant factors for survival for all patients (p < 0.001). The results indicate that MDT was a significant prognostic factor independent of clinical characteristics (HR: 2.095, 95% CI: 1.568-2.800, p < 0.001), with a significantly improved median survival (58.0 vs. 29.0 months, p < 0.001)., Conclusion: Based on PSM, MDT itself did have a real favorable prognostic significance for Chinese lung cancer patients in the study., (© 2023 John Wiley & Sons Australia, Ltd.)

Quercetin possesses multiple biological activities. To achieve efficient colon-specific release of quercetin, new composite nanofibers were developed by coating pH-responsive shellac on hydrophilic gelatin through coaxial electrospinning. These composite nanofibers contained bead-like structures. The encapsulation efficiency (87.6-98.5 %) and loading capacity (1.4-4.1 %) varied with increasing the initial quercetin addition amount (2.5-7.5 %). FTIR, XRD, and TGA results showed that the quercetin was successfully encapsulated in composite nanofibers in an amorphous state, with interactions occurring among quercetin, gelatin, and shellac. Composite nanofibers had pH-responsive surface wettability due to the shellac coating. In vitro digestion experiments showed that these composite nanofibers were highly stable in the upper gastrointestinal tract, with quercetin release ranging from 4.75 % to 12.54 %. In vivo organ distribution and pharmacokinetic studies demonstrated that quercetin could be sustainably released in the colon after oral administration of composite nanofibers. Besides, the enhanced anticancer activity of composite nanofibers was confirmed against HCT-116 cells by analyzing their effect on cell viability, cell cycle, and apoptosis. Overall, these novel composite nanofibers could deliver efficiently quercetin to the colon and achieve its sustained release, thus potential to regulate colon health. This system is also helpful in delivering other bioactives to the colon and exerting their functional effects., Competing Interests: Declaration of competing interest There have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A new compound, named coniferin B ( 1 ), and fourteen known compounds were purified and identified from the leaves and branches of Wikstroemia chamaedaphne Meisn. Their chemical structures were elucidated through analyzing spectroscopic and HRESIMS data. Compounds 2 , 3 , 5 , 7 - 9 , 11, and 13 were isolated from this plant for the first time. All compounds were assayed for cytotoxicity and activation of latent HIV activity on NH2 cells. The results showed that all compounds did not produce cytotoxicity at 10.0 μM and compounds 1 , 9 - 11 showed weak activating activity with activation folds of 4.88, 7.14, 5.3, and 6.97, respectively.

Regulation of the two-photon excited fluorescence (TPEF) emission intensity and wavelength of metal-organic framework (MOF) crystals with similar constitutions presents a significant challenge. In this study, two MOFs, Zn-BTPPA and Cd 3 -BTPPA, were constructed using tetrakis(1,1'-biphenyl-4-carboxylic acid)-1,4-benzenediamine (H 4 BTPPA) as the organic ligand and mononuclear Zn and trinuclear Cd 3 inorganic nodes, respectively. The incorporation of H 4 BTPPA within the MOF structures enables effective TPEF emission in both Zn-BTPPA and Cd 3 -BTPPA. The TPEF results show that Zn-BTPPA and Cd 3 -BTPPA exhibited strong emissions at 523 and 463 nm, respectively, when excited with a 780 nm laser. Moreover, Zn-BTPPA and Cd 3 -BTPPA exhibited much higher two-photon absorption cross sections, approximately 4.9 and 5.2 times higher than that of the reported dinuclear MOF, Cd 2 -BTPPA, with a similar composition, respectively. With different inorganic nodes, the stacking of chromophores, π···π interactions, and ligand geometry were found to correlate with the enhanced TPEF in Cd 3 -BTPPA and the blue-shifted TPEF in Zn-BTPPA. This work serves as an inspiration for designing efficient TPEF MOF materials based on the structure-property relationship.

Although the frequency of ancient hybridization across the Tree of Life is greater than previously thought, little work has been devoted to uncovering the extent, timeline, and geographic and ecological context of ancient hybridization. Using an expansive new dataset of nuclear and chloroplast DNA sequences, we conducted a multifaceted phylogenomic investigation to identify ancient reticulation in the early evolution of oaks (Quercus). We document extensive nuclear gene tree and cytonuclear discordance among major lineages of Quercus and relatives in Quercoideae. Our analyses recovered clear signatures of gene flow against a backdrop of rampant incomplete lineage sorting, with gene flow most prevalent among major lineages of Quercus and relatives in Quercoideae during their initial radiation, dated to the Early-Middle Eocene. Ancestral reconstructions including fossils suggest ancestors of Castanea + Castanopsis, Lithocarpus, and the Old World oak clade probably co-occurred in North America and Eurasia, while the ancestors of Chrysolepis, Notholithocarpus, and the New World oak clade co-occurred in North America, offering ample opportunity for hybridization in each region. Our study shows that hybridization-perhaps in the form of ancient syngameons like those seen today-has been a common and important process throughout the evolutionary history of oaks and their relatives. Concomitantly, this study provides a methodological framework for detecting ancient hybridization in other groups., (© 2024 Institute of Botany, Chinese Academy of Sciences.)

Limited open areas for urban agriculture and greenery have led to the search for innovative, sustainable growing media to strengthen the food supply and improve atmospheric quality for a resilient city. Rampant land developments have caused soil to become increasingly scarce. Sewage sludge incineration ash (SSIA), the by-product of waste-to-energy (WtE) incineration of sewage sludge, is a major municipal waste containing phosphorus-fertilizing nutrients. For the first time, we investigated the novel application of SSIA as a soilless plant-growing medium with built-in fertilizer. SSIA outperformed topsoil in bulk density, water-holding capacity, porosity, and nutrient content. However, it was found that SSIA has a high salinity and should be treated first. Wheatgrass (Triticum aestivum L.), a fast-growing glycophyte, thrived in the desalinated SSIA, showing growth and nutrient content comparable to the topsoil case. Simultaneously, it demonstrated phytoremediation. The SSIA residue was then recycled into cementitious materials, using desalinating water for mixing. SSIA upcycle into a growing medium facilitates urban resource management by utilizing nutrients in sewage waste for eco-friendly plant cultivation, benefiting urban agriculture and greenery. It is also a prudent valorization step before further recycling SSIA to reduce landfill requirements., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Chiral alcohols are essential building blocks of numerous pharmaceuticals and fine chemicals. Aldo-keto reductases (AKRs) constitute a superfamily of oxidoreductases that catalyze the reduction of aldehydes and ketones to their corresponding alcohols using NAD(P)H as a coenzyme. Knowledge about the crucial roles of AKRs immobilization in the biocatalytic synthesis of chiral alcohols is expanding. Herein, we reviewed the characteristics of various AKRs immobilization approaches, the applications of different immobilization materials, and the prospects of continuous flow bioreactor construction by employing these immobilized biocatalysts for synthesizing chiral alcohols. Finally, the opportunities and ongoing challenges for AKR immobilization are discussed and the outlook for this emerging area is analyzed., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yajun Wang reports financial support was provided by National Key Research and Development Program of China. Yajun Wang reports financial support was provided by Zhejiang Provincial Department of Science and Technology. none. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A stable lithium metal-organic framework, constructed using a redox-active N , N , N ', N '-tetrakis(4-carboxyphenyl)-1,4-phenylenediamine linker and Li 8 cluster-based one-dimensional rod secondary building unit, exhibits good stability and reversible redox activity. The Li 8 -MOF, which can be oxidized by AgNO 3 , has the potential to function as an electrochromic device, thereby advancing the development of smart MOF materials.

Objective: To investigate the effects of astragaloside IV (AS-IV) on podocyte injury of diabetic nephropathy (DN) and reveal its potential mechanism., Methods: In in vitro experiment, podocytes were divided into 4 groups, normal, high glucose (HG), inositol-requiring enzyme 1 (IRE-1) α activator (HG+thapsigargin 1 µmol/L), and IRE-1α inhibitor (HG+STF-083010, 20 µmol/L) groups. Additionally, podocytes were divided into 4 groups, including normal, HG, AS-IV (HG+AS-IV 20 µmol/L), and IRE-1α inhibitor (HG+STF-083010, 20 µmol/L) groups, respectively. After 24 h treatment, the morphology of podocytes and endoplasmic reticulum (ER) was observed by electron microscopy. The expressions of glucose-regulated protein 78 (GRP78) and IRE-1α were detected by cellular immunofluorescence. In in vivo experiment, DN rat model was established via a consecutive 3-day intraperitoneal streptozotocin (STZ) injections. A total of 40 rats were assigned into the normal, DN, AS-IV [AS-IV 40 mg/(kg·d)], and IRE-1α inhibitor [STF-083010, 10 mg/(kg·d)] groups (n=10), respectively. The general condition, 24-h urine volume, random blood glucose, urinary protein excretion rate (UAER), urea nitrogen (BUN), and serum creatinine (SCr) levels of rats were measured after 8 weeks of intervention. Pathological changes in the renal tissue were observed by hematoxylin and eosin (HE) staining. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect the expressions of GRP78, IRE-1α, nuclear factor kappa Bp65 (NF-κBp65), interleukin (IL)-1β, NLR family pyrin domain containing 3 (NLRP3), caspase-1, gasdermin D-N (GSDMD-N), and nephrin at the mRNA and protein levels in vivo and in vitro, respectively., Results: Cytoplasmic vacuolation and ER swelling were observed in the HG and IRE-1α activator groups. Podocyte morphology and ER expansion were improved in AS-IV and IRE-1α inhibitor groups compared with HG group. Cellular immunofluorescence showed that compared with the normal group, the fluorescence intensity of GRP78 and IRE-1α in the HG and IRE-1α activator groups were significantly increased whereas decreased in AS-IV and IRE-1α inhibitor groups (P<0.05). Compared with the normal group, the mRNA and protein expressions of GRP78, IRE-1α, NF-κ Bp65, IL-1β, NLRP3, caspase-1 and GSDMD-N in the HG group was increased (P<0.05). Compared with HG group, the expression of above indices was decreased in the AS-IV and IRE-1α inhibitor groups, and the expression in the IRE-1α activator group was increased (P<0.05). The expression of nephrin was decreased in the HG group, and increased in AS-IV and IRE-1α inhibitor groups (P<0.05). The in vivo experiment results revealed that compared to the normal group, the levels of blood glucose, triglyceride, total cholesterol, BUN, blood creatinine and urinary protein in the DN group were higher (P<0.05). Compared with DN group, the above indices in AS-IV and IRE-1α inhibitor groups were decreased (P<0.05). HE staining revealed glomerular hypertrophy, mesangial widening and mesangial cell proliferation in the renal tissue of the DN group. Compared with the DN group, the above pathological changes in renal tissue of AS-IV and IRE-1α inhibitor groups were alleviated. Quantitative RT-PCR and Western blot results of GRP78, IRE-1α, NF-κ Bp65, IL-1β, NLRP3, caspase-1 and GSDMD-N were consistent with immunofluorescence analysis., Conclusion: AS-IV could reduce ERS and inflammation, improve podocyte pyroptosis, thus exerting a podocyte-protective effect in DN, through regulating IRE-1α/NF-κ B/NLRP3 signaling pathway., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To explore the diagnostic efficacy of serum 14-3-3β protein combined with fractional exhaled nitric oxide (FeNO) and conventional ventilatory lung function parameters in diagnosing bronchial asthma (referred to as "asthma") in children., Methods: A prospective study included 136 children initially diagnosed with asthma during an acute episode as the asthma group, and 85 healthy children undergoing routine health checks as the control group. The study compared the differences in serum 14-3-3β protein concentrations between the two groups, analyzed the correlation of serum 14-3-3β protein with clinical indices, and evaluated the diagnostic efficacy of combining 14-3-3β protein, FeNO, and conventional ventilatory lung function parameters for asthma in children., Results: The concentration of serum 14-3-3β protein was higher in the asthma group than in the control group ( P <0.001). Serum 14-3-3β protein showed a positive correlation with the percentage of neutrophils and total serum immunoglobulin E, and a negative correlation with conventional ventilatory lung function parameters ( P <0.05). Cross-validation of combined indices showed that the combination of 14-3-3β protein, FeNO, and the percentage of predicted value of forced expiratory flow at 75% of lung volume had an area under the curve of 0.948 for predicting asthma, with a sensitivity and specificity of 88.9% and 93.7%, respectively, demonstrating good diagnostic efficacy ( P <0.001). The model had the best extrapolation., Conclusions: The combination of serum 14-3-3β protein, FeNO, and the percentage of predicted value of forced expiratory flow at 75% of lung volume can significantly improve the diagnostic efficacy for asthma in children. Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(7): 723-729 .

We present a theoretical framework to investigate thermoreversible phase transitions within polyzwitterion systems, encompassing macrophase separations (MPS) and gelation. In addition, we explore concentration fluctuations near critical points associated with MPS, as well as tricritical and bicritical points at the intersection of MPS and gelation. By utilizing mean-field percolation theory and field theory formalism, we derive the Landau free energy in terms of polyzwitterion concentration with fixed dipole strengths and other experimental variables, such as temperatures and salt concentrations. As the temperature decreases, the dipoles can form cross-links, resulting in polyzwitterion associations. The associations can grow to a gel network and enhance the propensity for MPS, including liquid-liquid, liquid-gel, and gel-gel phase separations. Remarkably, the associations also impact critical behaviors. Using the renormalization group technique, we find that the critical exponents of the polyzwitterion concentration correlation functions significantly deviate from those in the Ising universality class due to the presence of polyzwitterion associations, leading to crossover critical behaviors., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

The activated sludge process plays a crucial role in modern wastewater treatment plants. During the treatment of daily sewage, a large amount of residual sludge is generated, which, if improperly managed, can pose burdens on the environment and human health. Additionally, the highly hydrated colloidal structure of biopolymers limits the rate and degree of dewatering, making mechanical dewatering challenging. This study investigates the impact and mechanism of microwave irradiation (MW) in conjunction with peracetic acid (PAA) on the dewatering efficiency of sludge. Sludge dewatering effectiveness was assessed through capillary suction time (CST) and specific resistance to filtration (SRF). Examination of the impact of MW-PAA treatment on sludge dewatering performance involved assessing the levels of extracellular polymeric substances (EPS), employing three-dimensional excitation-emission matrix (3D-EEM), Fourier transform-infrared spectroscopy (FT-IR), and scanning electron microscopy. Findings reveal that optimal dewatering performance, with respective reductions of 91.22% for SRF and 84.22% for CST, was attained under the following conditions: microwave power of 600 W, reaction time of 120 s, and PAA dosage of 0.25 g/g MLSS. Additionally, alterations in both sludge EPS composition and floc morphology pre- and post-MW-PAA treatment underwent examination. The findings demonstrate that microwaves additionally boost the breakdown of PAA into •OH radicals, suggesting a synergistic effect upon combining MW-PAA treatment. These pertinent research findings offer insights into employing MW-PAA technology for residual sludge treatment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: To evaluate the effect of low-degree astigmatism on objective visual quality through the Optical Quality Analysis System (OQAS)., Methods: This study enrolled 46 participants (aged 23 to 30y, 90 eyes) with normal or corrected-to-normal vision. The cylindrical lenses (0, 0.5, 0.75, 1.0, and 1.25 D) were placed at the axial direction (180°, 45°, 90°, and 135°) in front of the eyes with the best correction to form 16 types of regular low-degree astigmatism. OQAS was used to detect the objective visual quality, recorded as the objective scattering index (OSI), OQAS values at contrasts of 100%, 20%, and 9% predictive visual acuity (OV100%, OV20%, and OV9%), modulation transfer function cut-off (MTF cut-off ) and Strehl ratio (SR). The mixed effect linear model was used to compare objective visual quality differences between groups and examine associations between astigmatic magnitude and objective visual quality parameters., Results: Apparent negative relationships between the magnitude of low astigmatism and objective visual quality were observed. The increase of OSI per degree of astigmatism at 180°, 45°, 90°, and 135° axis were 0.38 (95%CI: 0.35, 0.42), 0.50 (95%CI: 0.46, 0.53), 0.49 (95%CI: 0.45, 0.54) and 0.37 (95%CI: 0.34, 0.41), respectively. The decrease of MTF cut-off per degree of astigmatism at 180°, 45°, 90°, and 135° axis were -10.30 (95%CI: -11.43, -9.16), -12.73 (95%CI: -13.62, -11.86), -12.75 (95%CI: -13.79, -11.70), and -9.97 (95%CI: -10.92, -9.03), respectively. At the same astigmatism degree, OSI at 45° and 90° axis were higher than that at 0° and 135° axis, while MTF cut-off were lower., Conclusion: Low astigmatism of only 0.50 D can significantly reduce the objective visual quality., Competing Interests: Conflicts of Interest: Ye LY, None; Li SF, None; Zuo JJ, None; Li J, None; Ma HX, None., (International Journal of Ophthalmology Press.)

Investigating novel nonlinear optical (NLO) active units serves as a valuable method for broadening the research landscape of NLO materials. This study showcases the potential of the cytosinium cation (C 4 H 6 N 3 O) + as a novel NLO-active motif through theoretical calculations. The title compound exhibited a wide band gap of 3.85 eV, along with a moderate second harmonic generation (SHG) response of 1.65 times that of KH 2 PO 4 (KDP) and significant birefringence of 0.47. Its exceptional optical properties are primarily attributed to the synergy interaction between cations and anionic groups in the asymmetric unit.

Over the years, a number of state-of-the-art data analysis tools have been developed to provide a comprehensive analysis of data collected from gas chromatography-mass spectrometry (GC-MS). Unfortunately, the time shift problem remains unsolved in these tools. Here, we developed a novel comprehensive data analysis strategy for GC-MS-based untargeted metabolomics (AntDAS-GCMS) to perform total ion chromatogram peak detection, peak resolution, time shift correction, component registration, statistical analysis, and compound identification. Time shift correction was specifically optimized in this work. The information on mass spectra and elution profiles of compounds was used to search for inherent landmarks within analyzed samples to resolve the time shift problem across samples efficiently and accurately. The performance of our AntDAS-GCMS was comprehensively investigated by using four complex GC-MS data sets with various types of time shift problems. Meanwhile, AntDAS-GCMS was compared with advanced GC-MS data analysis tools and classic time shift correction methods. Results indicated that AntDAS-GCMS could achieve the best performance compared to the other methods.

Alkaline earth (AE) metal complexes have garnered significant interest in various functional fields due to their nontoxicity, low density, and low cost. However, there is a lack of systematic investigation into the structural characteristics and physical properties of AE-metal-organic frameworks (MOFs). In this research, we synthesized isostructural MOFs consisting of AE 4 (μ 4 -Cl) clusters bridged by benzo-(1,2;3,4;5,6)-tris(thiophene-2'-carboxylic acid) (BTTC 3- ) ligands. The resulting structure forms a truncated octahedral cage denoted as [AE 4 (m 4 -Cl)] 6 (BTTC) 8 , which further linked to a porous three-dimensional framework. Among the investigated AE ions (Ca, Sr, and Ba), the Ca 4 -MOF demonstrated good chemical stability in water compared to Sr 4 -MOF and Ba 4 -MOF. The N 2 adsorption and solid-state UV-vis-NIR absorption behaviors were evaluated for all AE 4 -MOFs, showing similar trends among the different metal ions. Additionally, the proton conduction study revealed that the Ca 4 -MOF exhibited ultra-high proton conductivity, reaching 3.52×10 -2  S cm -1 at 343 K and 98 % RH. Notably, the introduction of LiCl via guest exchange resulted in an improved proton conduction of up to 6.36×10 -2  S cm -1 under similar conditions in the modified LiCl@Ca 4 -MOF. The findings shed light on the regulation of physical properties and proton conductivity of AE-MOFs, providing valuable insights for their potential applications in various fields., (© 2024 Wiley-VCH GmbH.)

In this study, a green and efficient enrichment method for the four majors active diterpenoid components: pimelotide C, pimelotide A, simplexin, and 6α,7α-epoxy-5β-hydroxy-12-deoxyphorbol-13-decanoate in the buds of Wikstroemia chamaedaphne was established using macroporous resin chromatography. The adsorption and desorption rates of seven macroporous resins were compared using static tests. The D101 macroporous resin exhibited the best performance. Static and dynamic adsorption tests were performed to determine the enrichment and purification of important bioactive diterpenoids in the buds of W. chamaedaphne. Diterpenoid extracts were obtained by using D101 macroporous resin from the crude extracts of W. chamaedaphne. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis demonstrated that most of the diterpenoids were enriched in diterpenoid extracts. These results confirmed that diterpenoids in the buds of W. chamaedaphne could be enriched using macroporous resin technology, and the enriched diterpenoid extracts showed more efficient activation of the latent human immunodeficiency virus. This study provides a novel strategy for discovering efficient and low-toxicity latency-reversing agents and a potential basis for the comprehensive development and clinical application of the buds of W. chamaedaphne., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Efferocytosis is a crucial process whereby phagocytes engulf and eliminate apoptotic cells (ACs). This intricate process can be categorized into four steps: (1) ACs release "find me" signals to attract phagocytes, (2) phagocytosis is directed by "eat me" signals emitted by ACs, (3) phagocytes engulf and internalize ACs, and (4) degradation of ACs occurs. Maintaining immune homeostasis heavily relies on the efficient clearance of ACs, which eliminates self-antigens and facilitates the generation of anti-inflammatory and immunosuppressive signals that maintain immune tolerance. However, any disruptions occurring at any of the efferocytosis steps during apoptosis can lead to a diminished efficacy in removing apoptotic cells. Factors contributing to this inefficiency encompass dysregulation in the release and recognition of "find me" or "eat me" signals, defects in phagocyte surface receptors, bridging molecules, and other signaling pathways. The inadequate clearance of ACs can result in their rupture and subsequent release of self-antigens, thereby promoting immune responses and precipitating the onset of autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, and multiple sclerosis. A comprehensive understanding of the efferocytosis process and its implications can provide valuable insights for developing novel therapeutic strategies that target this process to prevent or treat autoimmune diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The sex of dioecious plants is mainly determined by genetic factors, but it can also be converted by environmental cues such as exogenous phytohormones. Gibberellic acids (GAs) are well-known inducers of flowering and sexual development, yet the pathway of gibberellin-induced sex conversion in dioecious spinach (Spinacia oleracea L.) remains elusive. Based on sex detection before and after GA 3 application using T11A and SSR19 molecular markers, we confirmed and elevated the masculinization effect of GA on a single female plant through exogenous applications of GA 3 , showing complete conversion and functional stamens. Silencing of GIBBERELLIC ACID INSENSITIVE (SpGAI), a single DELLA family protein that is a central GA signaling repressor, results in similar masculinization. We also show that SpGAI can physically interact with the spinach KNOX transcription factor SHOOT MERISTEMLESS (SpSTM), which is a homolog of the flower meristem identity regulator STM in Arabidopsis. The silencing of SpSTM also masculinized female flowers in spinach. Furthermore, SpSTM could directly bind the intron of SpPI to repress SpPI expression in developing female flowers. Overall, our results suggest that GA induces a female masculinization process through the SpGAI-SpSTM-SpPI regulatory module in spinach. These insights may help to clarify the molecular mechanism underlying the sex conversion system in dioecious plants while also elucidating the physiological basis for the generation of unisexual flowers so as to establish dioecy in plants., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

Background: Previous studies had found that the mechanical methods were as effective as pharmacological methods in achieving vaginal delivery. However, whether balloon catheter induction is suitable for women with severe cervical immaturity and whether it will increase the related risks still need to be further explored., Research Aim: To evaluate the efficacy and safety of Foley catheter balloon for labor induction at term in primiparas with different cervical scores., Methods: A total of 688 primiparas who received cervical ripening with a Foley catheter balloon were recruited in this study. They were divided into 2 groups: Group 1 (Bishop score ≤ 3) and Group 2 (3 < Bishop score < 7). Detailed medical data before and after using of balloon were faithfully recorded., Results: The cervical Bishop scores of the two groups after catheter placement were all significantly higher than those before (Group 1: 5.49 ± 1.31 VS 2.83 ± 0.39, P<0.05; Group 2: 6.09 ± 1.00 VS 4.45 ± 0.59, P<0.05). The success rate of labor induction in group 2 was higher than that in group 1 (P<0.05). The incidence of intrauterine infection in Group 1 was higher than that in Group 2 (18.3% VS 11.3%, P<0.05)., Conclusion: The success rates of induction of labor by Foley catheter balloon were different in primiparas with different cervical conditions, the failure rate of induction of labor and the incidence of intrauterine infection were higher in primiparas with severe cervical immaturity., (© 2024. The Author(s).)

We study the role of active coupling on the transport properties of homogeneously charged macromolecules in an infinitely dilute solution. An enzyme becomes actively bound to a segment of the macromolecule, exerting an electrostatic force on it. Eventually, thermal fluctuations cause it to become unbound, introducing active coupling into the system. We study the mean-squared displacement (MSD) and find a new scaling regime compared to the thermal counterpart in the presence of hydrodynamic and segment-segment electrostatic interactions. Furthermore, the study of segment-segment equal-time correlation reveals the swelling of the macromolecule. Further, we derive the concentration equation of the macromolecule with active binding and study how the cooperative diffusivity of the macromolecules get modified by its environment, including the macromolecules itself. It turns out that these active fluctuations enhance the effective diffusivity of the macromolecules. The derived closed-form expression for diffusion constant is pertinent to the accurate interpretation of light scattering data in multi-component systems with binding-unbinding equilibria.

The design and synthesis of stable porous materials capable of removing both hard and soft metal ions pose a significant challenge. In this study, a novel metal-organic framework (MOF) adsorbent named CdK- m -COTTTB was developed. This MOF material was constructed using sulfur-rich m -cyclooctatetrathiophene-tetrabenzoate ( m -H 4 COTTTB) as the organic ligand and oxygen-rich bimetallic clusters as the inorganic nodes. The incorporation of both soft and hard base units within the MOF structure enables effective removal of various heavy metal ions, including both soft and hard acid species. In single-component experiments, the adsorption capacity of CdK- m -COTTTB for Pb 2+ , Tb 3+ , and Zr 4+ ions reached levels of 636.94, 432.90, and 357.14 mg·g -1 , respectively, which is comparable to specific MOF absorbents. The rapid adsorption process was found to be chemisorption. Furthermore, CdK- m -COTTTB exhibited the capability to remove at least 12 different metal ions in both separate and multicomponent solutions. The material demonstrated excellent acid-base stability and renewability, which are advantageous for practical applications. CdK- m -COTTTB represents the first reported pristine MOF material for the removal of both hard and soft acid metal ions. This work serves as inspiration for the design and synthesis of porous crystalline materials that can efficiently remove diverse heavy metal pollutants.

To investigate the association of gene polymorphisms of TNF-α-308G/A rs1800629 with the susceptibility and severity of rheumatoid arthritis (RA), literature from PubMed, EMBASE, Web of Science and CNKI databases was searched. Two authors screened the literature independently, extracted data and evaluated the risk of bias of the included studies. According to the inclusion and exclusion criteria, five genetic models were established: The allelic model (A vs. G), dominant model (GA + AA vs. GG), recessive model (AA vs. GG + GA), co-dominant model (AA vs. GG) and super-dominant model (GG + AA vs. GA). Stata 17.0 software was used for the meta-analysis. A total of 34 eligible studies with 12,611 subjects were included, including 6,030 cases in the RA group and 6,581 controls. Meta-analysis calculations revealed that the genetic polymorphisms of TNF-α-308G/A rs1800629 were not significantly associated with susceptibility to RA, with an odds ratio and 95% confidence interval (CI) for each genetic model [A vs. G: 0.937 (0.762-1.152); GA + AA vs. GG: 0.918 (0.733-1.148); AA vs. GG + GA: 1.131 (0.709-1.802); AA vs. GG: 1.097 (0.664-1.813); and GG + AA vs. GA: 1.108 (0.894-1.373)]. For the association between TNF-α-308G/A rs1800629 gene polymorphisms and the severity of RA, the results of subgroup analysis calculations showed that TNF-α-308G/A rs1800629 gene polymorphisms were associated with the severity of RA in European populations, with the gene model and 95% CI [GA + AA vs. GG: 0.503 (0.297-0.853); and GG + AA vs. GA: 2.268 (1.434-3.590)]. When assessing the confidence in the positive results of the present study through the false-positive report probability, the positive results were observed to be reliable. No significant association was observed between genetic polymorphisms in TNF-α-308G/A rs1800629 and susceptibility to RA. However, a significant association exists with the severity of RA in European populations., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Wang et al.)

Life-threatening allergic reactions to food allergens, particularly peanut protein Ara h1, are a growing public health concern affecting millions of people worldwide. Thus, accurate and rapid detection is necessary for allergen labeling and dietary guidance and ultimately preventing allergic incidents. Herein, we present a novel ratiometric fluorescence aptasensor based on multivalent aptamer-encoded DNA flowers (Mul-DNFs) for the high-stability and sensitive detection of allergen Ara h1. The flower-shaped Mul-DNFs were spontaneously packaged using ultralong polymeric DNA amplicons driven by a rolling circle amplification reaction, which contains a large number of Ara h1 specific recognition units and has excellent binding properties. Furthermore, dual-color fluorescence-labeled Mul-DNFs probes were developed by hybridizing them with Cy3- and Cy5-labeled complementary DNA (cDNA) to serve as a ratiometric fluorescence aptasensor platform based on fluorescence resonance energy transfer. Benefiting from the combined merits of the extraordinary synergistic multivalent binding ability of Mul-DNFs, the excellent specificity of the aptamer, and the sensitivity of the ratiometric sensor to avoid exogenous interference. The developed ratiometric aptasensor showed excellent linearity (0.05-2000 ng mL -1 ) with a limit of detection of 0.02 ng mL -1 . Additionally, the developed ratiometric fluorescence aptasensor was utilized for quantifying the presence of Ara h1 in milk, infant milk powder, cookies, bread, and chocolate with recoveries of 95.7-106.3%. The proposed ratiometric aptasensor is expected to be a prospective universal aptasensor platform for the rapid, sensitive, and accurate determination of food and environmental hazards.

Background: Clinical belonging refers to the feeling that clinical medical staff feel recognized and accepted by others or groups. The level of clinical belonging of nursing interns affects students' learning motivation and confidence, which in turn affects their clinical practice behavior., Aim: To explore the effects of professional identity and nursing information ability on clinical belonging among nursing interns and establish a relationship model for these factors., Methods: The researchers used the convenience sampling method to select 682 nursing interns from China. The survey was conducted using a general information questionnaire, clinical sense of belonging scale, nursing information ability self-assessment scale, and a nursing student professional identity questionnaire. The mediating effect of nursing information ability between their professional identity and clinical sense of belonging was analyzed using SPSS 21.0 and the path analysis in structural equation modeling., Results: The total scores of clinical belonging, professional identity, and nursing information ability of nursing interns were (104.29 ± 13.11) points, (57.89 ± 7.16) points, and (70.29 ± 6.20) points, respectively. Nursing information ability had a direct effect on the clinical sense of belonging (effect value = 0.46, P < 0.05). Occupational identity had a direct effect (effect value = 0.52, P < 0.05) and an indirect effect (effect value = 0.21, P < 0.05) on clinical belonging., Conclusion: Nursing administrators in nursing colleges and hospitals should take effective measures to improve the professional identity and nursing information ability of nursing interns, as well as the clinical sense of belonging among nursing interns., Competing Interests: Conflict-of-interest statement: All authors have no conflicts of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

In this study, the feasibility of shellac nanofibers as carrier system for colonic delivery of quercetin was evaluated. Firstly, the nanofibers without and with different amounts (2.5 %, 5.0 %, and 7.5 %) of quercetin were fabricated using pure shellac as a carrier by electrospinning. The morphology of nanofibers was bead-shape confirmed by SEM. FTIR, XRD, and DSC analysis showed that quercetin was encapsulated into shellac nanofibers, forming an amorphous complex. The molecular docking simulation indicated quercetin bound well to shellac through hydrogen bonding and van der Waals forces. These nanofibers had higher thermal stability than pure quercetin, and their surface wettability exhibited a pH-responsive behavior. The loading capacity of quercetin varied from 2.25 % to 6.84 % with the increased amount of quercetin, and it affected the stability of nanofibers in food simulants by measuring the release profiles of quercetin. The shellac nanofibers had high gastrointestinal stability, with a minimum quercetin release of 16.87 % in simulated digestive fluids, while the remaining quercetin was delivered to the colon and was released gradually. Moreover, the nanofibers exerted enhanced anticancer activity against HCT-116 cells by arresting cell cycle in G0/G1 phase and inducing cell apoptosis. Overall, shellac nanofibers are promising materials for colon-targeted delivery of active compounds., Competing Interests: Declaration of competing interest There have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To investigate the effect of isorhamnetin on the pathology of rheumatoid arthritis (RA)., Methods: Tumor necrosis factor (TNF)- α -induced fibroblast-like synoviocytes (FLS) was exposed to additional isorhamnetin (10, 20 and 40 µ mol/L). Overexpression vectors for matrix metalloproteinase-2 (MMP2) or MMP9 or SRC were transfected to explore their roles in isorhamnetin-mediated RA-FLS function. RA-FLS viability, migration, and invasion were evaluated. Moreover, a collagen-induced arthritis (CIA) rat model was established. Rats were randomly divided to sham, CIA, low-, medium-, and high-dosage groups using a random number table (n=5 in each group) and administed with normal saline or additional isorhamnetin [2, 10, and 20 mg/(kg·day)] for 4 weeks, respectively. Arthritis index was calculated and synovial tissue inflammation was determined in CIA rats. The levels of MMP2, MMP9, TNF-α, interleukin-6 (IL-6), and IL-1 β, as well as the phosphorylation levels of SRC, extracellular regulated kinase (ERK), and cyclic adenosine monophosphate response element-binding (CREB), were detected in RA-FLS and synovial tissue. Molecular docking was also used to analyze the binding of isorhamnetin to SRC., Results: In in vitro studies, isorhamnetin inhibited RA-FLS viability, migration and invasion (P<0.05). Isorhamnetin downregulated the levels of MMP2, MMP9, TNF-α, IL-6, and IL-1 β in RA-FLS (P<0.05). The overexpression of either MMP2 or MMP9 reversed isorhamnetin-inhibited RA-FLS migration and invasion, as well as the levels of TNF-α, IL-6, and IL-1 β (P<0.05). Furthermore, isorhamnetin bound to SRC and reduced the phosphorylation of SRC, ERK, and CREB (P<0.05). SRC overexpression reversed the inhibitory effect of isorhamnetin on RA-FLS viability, migration and invasion, as well as the negative regulation of MMP2 and MMP9 (P<0.05). In in vivo studies, isorhamnetin decreased arthritis index scores (P<0.05) and alleviated synovial inflammation. Isorhamnetin reduced the levels of MMP2, MMP9, TNF-α, IL-6, and IL-1 β, as well as the phosphorylation of SRC, ERK, and CREB in synovial tissue (P<0.05). Notably, the inhibitory effect of isorhamnetin was more pronounced at higher concentrations (P<0.05)., Conclusion: Isorhamnetin exhibited anti-RA effects through modulating SRC/ERK/CREB and MMP2/MMP9 signaling pathways, suggesting that isorhamnetin may be a potential therapeutic agent for RA., (© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To evaluate the diagnostic value of gene testing in familial hypercholesterolemia (FH) in patients with premature myocardial infarction(PMI). Methods: This study was a single center cross-sectional study. A retrospective analysis was made on PMI patients who visited the People's Hospital of Peking University from May 1, 2015 to March 31, 2017. Clinical data of patients was collected and gene testing of FH related genes low density lipoprotein receptor (LDLR), proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein B(APOB) and low density lipoprotein receptor adaptor protein 1(LDLRAP1) was carried out. Clinical diagnosis of FH patients was performed using Simon Broome criteria, DLCN criteria, and FH Chinese expert consensus. Results: There were 188 males (83.6%) among 225 PMI patients, and the age of the first myocardial infarction was (46.6±7.2) years old. Ten patients carried FH pathogenic or possibly pathogenic mutations (4.4%). Compared with Simon Broome standard, DLCN standard and FH Chinese expert consensus, gene testing increased the diagnostic rate of FH by 53.3%, 33.3% and 42.1% respectively. Conclusion: Gene testing is helpful to improve the diagnosis of FH, and it is important to start the standard treatment of FH as early as possible in patients with premature myocardial infarction.