Preparation and structural characterization of chitosan­sodium alginate nanocapsules and their effects on the stability and antioxidant activity of blueberry anthocyanins.

This study prepared a nanocapsule (NPs) from chitosan (CS) and sodium alginate (ALG) and used them to enhance the stability of blueberry anthocyanins (BA) The optimal NPs was obtained at pH value of 3.25, BA concentration of 0.5 mg/mL and mixing ratio of CS to ALG of 1:1 (W/W). Further, the formation of composite NPs was confirmed by a series of characterization methods. The CS-BA-ALG NPs appeared spherical, smooth, and evenly distributed when observed under an optical microscope and transmission Electron Microscope. The X-ray Diffractometer and Fourier Transform Infrared spectroscopy data proved that electrostatic interaction and hydrogen bonding are dominant forces to form NPs. Thermogravimetric analysis and differential scanning calorimetry results demonstrated that the CS-BA-ALG NPs system significantly improved the thermal stability of anthocyanins. In addition, it was also proved that CS-BA-ALG NPs showed high antioxidant capacity and protection capacity.

The Efficacy and Safety Assessment of Sequential Liposuction Modified Double Ring Areola Incision in Moderate and Severe Breast Ptosis Correction.

Background: A total of 42 cases of moderate and severe breast ptosis were treated with sequential liposuction modified double ring areola incision surgery (experimental group), and 45 cases were treated with traditional double ring areola incision alone surgery (control group). Methods: They were followed up for 6 months after the operation. The scar formation and breast ptosis repair were observed, and postoperative complications and patient satisfaction were monitored. Results: Better results such as improved postoperative breast appearance were achieved in the sequential liposuction modified double ring areola incision group compared with the double ring areola incision alone group. After treatment, the distance between the midpoint of the inframammary fold and the nipple, the distance between the suprasternal fossa, and the nipple of the two groups were lower than those before treatment. The distance between the midpoint of the inframammary fold and the nipple showed no difference between the two experimental groups. The distance between the suprasternal fossa and the nipple of the experimental group were lower compared with the control group. Lower complication rates and higher satisfaction rates were observed in patients treated with sequential liposuction modified double ring areola incision. The patients in the experimental group were more satisfied with breast symmetry, breast shape, and breast size than those in the control group. Conclusions: The treatment with sequential liposuction modified double ring areola incision was effective and safe compared with double ring areola incision alone. It could improve the breast shape of patients, improve the satisfaction of patients, and reduce the occurrence of complications.

Ultrasound-assisted glycosylation of ovalbumin and dextran conjugate carrier for anthocyanins and their stability evaluation.

Anthocyanins (AC) are vulnerable to degradation when affected by external factors. The present study employed ultrasound-assisted glycosylation of ovalbumin (OVA) and dextran (Dex) to generate conjugate carrier for AC to improve its stability. The results showed that sonication significantly improved the progression of Maillard reaction to OVA. Compared to traditional glycosylation, ultrasound treatment showed a higher degree of grafting, a lower number of free-SH, and smaller particle size and uniform distribution. The SDS-PAGE results indicated covalent interaction. Intrinsic fluorescence (INF), Fourier transform infrared spectroscopy (FTIR), and Circular dichroism (CD) analysis results suggested that ultrasound-assisted glycosylation altered the OVA structure. The scanning electron microscope (SEM) and X-ray diffractometer (XRD) observed that the ultrasound-assisted complex had a more compact and smoother structure and protein unfolding were better. The protein solubility increased significantly after glycosylation. Thermal gravimetric analysis (TGA) and Differential scanning calorimetry (DSC) indicated that the glycosylated conjugates can significantly improve the thermal stability of AC In addition, the AC showed an improved processing and storage stability when conjugated with glycosylated carrier. The glycosylated protein-anthocyanins complex may help provide new ideas and scientific basis for the development of naturally sourced anthocyanins-relevant products in pharmaceutical and food industry applications.

Dynamic functional network connectivity in children with profound bilateral congenital sensorineural hearing loss.

BACKGROUND: Functional magnetic resonance imaging (fMRI) studies have revealed extensive functional reorganization in patients with sensorineural hearing loss (SNHL). However, almost no study focuses on the dynamic functional connectivity after hearing loss. OBJECTIVE: This study aimed to investigate dynamic functional connectivity changes in children with profound bilateral congenital SNHL under the age of 3 years. MATERIALS AND METHODS: Thirty-two children with profound bilateral congenital SNHL and 24 children with normal hearing were recruited for the present study. Independent component analysis identified 18 independent components composing five resting-state networks. A sliding window approach was used to acquire dynamic functional matrices. Three states were identified using the k-means algorithm. Then, the differences in temporal properties and the variance of network efficiency between groups were compared. RESULTS: The children with SNHL showed longer mean dwell time and decreased functional connectivity between the auditory network and sensorimotor network in state 3 (P < 0.05), which was characterized by relatively stronger functional connectivity between high-order resting-state networks and motion and perception networks. There was no difference in the variance of network efficiency. CONCLUSIONS: These results indicated the functional reorganization due to hearing loss. This study also provided new perspectives for understanding the state-dependent connectivity patterns in children with SNHL.

Pharmacokinetics and Bioavailability Study of a Novel Smoothened Inhibitor TPB15 for Treatment of Triple-Negative Breast Cancer in Rats by High Performance Liquid Chromatography-Mass Spectrometry.

BACKGROUND AND OBJECTIVES: Smoothened (SMO), a key component of the hedgehog signaling pathway, represents a therapeutic target for triple negative breast cancer (TNBC), yet the chemotherapy response rate in TNBC patients is only 40-50%, underscoring the urgent need for the development of novel drugs to effectively treat this condition. The novel compound TPB15, an SMO inhibitor derived from [1,2,4] triazolo [4,3-α] pyridines, demonstrated superior anti-TNBC activity and lower toxicity compared to the first SMO inhibitor vismodegib in both in vitro and in vivo. However, the compound's pharmacokinetic properties remain unclear. The present work aims to develop a simple HPLC-MS/MS method to profile the pharmacokinetics and bioavailability of TPB15 in rats as a ground work for further clinical research. METHODS: Separation was performed on an Agilent ZORBAX StableBond C18 column by gradient elution using acetonitrile and 0.1% formic acid as mobile phase at a flow rate of 0.3 mL/min. Multiple reaction monitoring(MRM) in positive mode with the transitions of m/z 454.2 → 100.0, 248.1 → 121.1 was employed to determine TPB15 and internal standard tinidazole, respectively. The specificity, intra- and inter- day precision and accuracy, extraction recovery, stability, matrix effect, dilution integrity and carryover of the method was validated. The pharmacokinetics and bioavailability  study of TPB15 were carried out on rats through intravenous injection at the dose of 5 mg/kg and oral gavage at the dose of 25 mg/kg, and the pharmacokinetics parameters were calculated by the non-compartment analysis using the pharmacokinetics software DAS 2.1.1. RESULTS: The values of specificity, intra- and inter- day precision and accuracy, extraction recovery, stability, matrix effect, dilution integrity and carryover satisfied the acceptable limits. The lower limit of quantification of this method was 10 ng/mL with a linear range of 10-2000 ng/mL. The validated method was then applied to pharmacokinetics and bioavailability studies in rat by dosing with gavage (25 mg/kg) and intravenous injection(5 mg/kg), and the oral bioavailability of TBP15 in rat was calculated as 16.4 ± 3.5%. The pharmacokinetic parameters were calculated as following: maximum of plasma concentration (Cmax) (PO: 2787.17 ± 279.45 µg/L), Time to maximum plasma concentration (Tmax) (PO: 4.20 ± 0.90 h), the area under the concentration-time curve 0 to time (AUC0-t) (PO: 17,373.03 ± 2585.18 ng/mL·h, IV: 21,129.79 ± 3360.84 ng/mL·h), the area under the concentration-time curve 0 to infinity (AUC0-∞) (PO: 17,443.85 ± 2597.63 ng/mL·h, IV: 17,443.85 ± 2597.63 ng/mL·h), terminal elimination half-life (t1/2) (PO: 7.26 ± 2.16 h, IV: 4.78 ± 1.09 h). CONCLUSIONS: TPB15, a promising candidate for treating TNBC, has demonstrated outstanding efficacy and safety in vitro and in vivo. This study established a simple, sensitive, and rapid HPLC-MS/MS bioanalytical method, developed and validated in accordance with FDA and EMA guidelines, for conducting pharmacokinetic and bioavailability studies of TPB15. The results revealed a favorable pharmacokinetic profile owing to its long t1/2. Nevertheless, the next phase of research should include formulation screening to enhance bioavailability, as well as clinical trials, metabolism pathway analysis, and assessment of potential drug-drug interactions.

A Rapid One-Pot Workflow for Sensitive Microscale Phosphoproteomics.

Compared to advancements in single-cell proteomics, phosphoproteomics sensitivity has lagged behind due to low abundance, complex sample preparation, and substantial sample input requirements. We present a simple and rapid one-pot phosphoproteomics workflow (SOP-Phos) integrated with data-independent acquisition mass spectrometry (DIA-MS) for microscale phosphoproteomic analysis. SOP-Phos adapts sodium deoxycholate based one-step lysis, reduction/alkylation, direct trypsinization, and phosphopeptide enrichment by TiO2 beads in a single-tube format. By reducing surface adsorptive losses via utilizing n-dodecyl ß-d-maltoside precoated tubes and shortening the digestion time, SOP-Phos is completed within 3-4 h with a 1.4-fold higher identification coverage. SOP-Phos coupled with DIA demonstrated >90% specificity, enhanced sensitivity, lower missing values (<1%), and improved reproducibility (8%-10% CV). With a sample size-comparable spectral library, SOP-Phos-DIA identified 33,787 ± 670 to 22,070 ± 861 phosphopeptides from 5 to 0.5 µg cell lysate and 30,433 ± 284 to 6,548 ± 21 phosphopeptides from 50,000 to 2,500 cells. Such sensitivity enabled mapping key lung cancer signaling sites, such as EGFR autophosphorylation sites Y1197/Y1172 and drug targets. The feasibility of SOP-Phos-DIA was demonstrated on EGFR-TKI sensitive and resistant cells, revealing the interplay of multipathway Hippo-EGFR-ERBB signaling cascades underlying the mechanistic insight into EGFR-TKI resistance. Overall, SOP-Phos-DIA is an efficient and robust protocol that can be easily adapted in the community for microscale phosphoproteomic analysis.

Chronic mitral regurgitation predicts acute heart failure and worse outcomes after endovascular treatment for large vessel occlusion stroke.

BACKGROUND: Valvular diseases are widely recognized as important etiologies for large vessel occlusion stroke (LVO) but their impact on outcomes among patients with LVO receiving endovascular treatment (EVT) are less well delineated. METHODS: This study was a post hoc exploratory analysis of the RESCUE-BT trial, DEVT trial and BASILAR prospective registry. Outcome measures included the modified Rankin Scale (mRS) score at 90 days, symptomatic intracranial hemorrhage, and post-stroke early acute heart failure (EAHF). Chronic significant mitral regurgitation (csMR) was defined as a long-existing mitral regurgitation (MR) with moderate-to-severe MR grade examined by the transthoracic echocardiography. Adjusted odds ratio (aOR) and 95% confidence interval (CI) were obtained by logistic regression models. RESULTS: Among 2011 patients in these three studies, 837 individuals receiving EVT with available information for valvular status were included in this study. In all categories of chronic valvular disorders, only csMR was related to very poor outcomes (mRS 5-6, aOR 2.76 (95% CI 1.59 to 4.78), P<0.001). CsMR (aOR 7.65 (95% CI 4.33 to 13.49), P<0.001) was an independent predictor of post-stroke EAHF. Mediation analysis showed that csMR increased EAHF instead of reocclusion events or venous thrombosis mediated its effects on functional outcome (49.50% (95% CI 24.83% to 90.00%)). Identical results of csMR on clinical outcomes and post-stroke EAHF were detected in novel cohorts constructed by propensity score matching and sensitivity analysis. CONCLUSION: Our study demonstrated that csMR was a mediator of heart-brain interaction associated with poor outcomes of LVO after EVT by increasing the frequency of post-stroke EAHF. Replication of these findings in a larger cohort is warranted.

Association of Renal Impairment with Clinical Outcomes Following Endovascular Therapy in Acute Basilar Artery Occlusion.

Purpose: Renal impairment (RI) is associated with unfavourable outcome after acute ischaemic stroke with anterior circulation large vessel occlusion. We assessed the association of RI with clinical outcomes in patients with acute basilar artery occlusion (ABAO), and the impact of RI on the effects of endovascular therapy (EVT) versus standard medical treatment (SMT). Patients and Methods: We used data from the BASILAR registry, an observational, prospective, nationwide study of patients with ABAO in routine clinical practice in China. Baseline estimated glomerular filtration rate (eGFR) was recorded at admission. The primary outcome was the modified Rankin Scale (mRS) score at 90 days. Secondary outcomes included favourable outcome (mRS score 0-3), mortality, and symptomatic intracranial haemorrhage (sICH). Multivariate logistic regression was used to assess the association of RI with mortality and functional improvement at 90 days. Results: Among 829 patients enrolled, 747 patients were analysed. The median baseline eGFR was 89 mL/min/1.73m2 (IQR, 71-100), and 350 (46.8%), 297 (39.8%), and 100 (13.4%) patients had baseline eGFR values of ≥90, 60-89, and <60 mL/min/1.73m2, respectively. RI was associated with increased mortality (adjusted odds ratio [aOR], 1.97; 95% CI, 1.15-3.67) at 90 days and decreased survival probability (aOR 1.74; 95% CI, 1.30-2.33) within 1 year. EVT was associated with better functional improvement (common aOR, 2.50; 95% CI, 1.43-4.35), favourable outcome (aOR 5.42; 95% CI, 1.92-15.29) and lower mortality (aOR 0.47; 95% CI, 0.25-0.88) in ABAO patients with eGFR ≥90 mL/min/1.73m2. However, RI was not modified the relationship of EVT with functional improvement (common aOR, 3.03; 95% CI, 0.81-11.11), favourable outcome (aOR 2.10; 95% CI, 0.45-9.79), and mortality (aOR 0.56; 95% CI, 0.15-2.06) by eGFR categories. Conclusion: RI is associated with reduced efficacy of EVT and worse functional outcome and higher mortality at 3 months and lower survival probability at 1 year in patients with ABAO.

Characterization and mechanical removal of metallic aluminum (Al) embedded in weathered municipal solid waste incineration (MSWI) bottom ash for application as supplementary cementitious material.

Municipal solid waste incineration (MSWI) bottom ash, due to its high mineral content, presents great potential as supplementary cementitious material (SCM). Weathering, also known as aging, is a treatment process commonly employed in waste management to minimize the risk of heavy metal leaching from MSWI bottom ash. Using weathered MSWI bottom ash to produce blended cement pastes is considered as a high-value-added and sustainable waste disposal solution. However, a critical challenge arises from the metallic aluminum (Al) in weathered MSWI bottom ash, which is known to induce detrimental effects such as volume expansion and strength loss of blended cement pastes. While most metallic Al in weathered MSWI bottom ash can be removed with eddy current separators in metal recovery plants, the residual metallic Al, owing to its small particle size, cannot be removed with the same technique. This study is dedicated to addressing this issue. An in-depth analysis was conducted on residual metallic Al embedded in weathered MSWI bottom ash particles, aiming to guide the removal of this metal. This analysis revealed that mechanical removal was the most suitable method for extracting metallic Al. The specific processes and mechanisms underlying this method were elucidated. After reducing metallic Al content in weathered MSWI bottom ash by 77 %, a significant improvement in the quality of blended cement pastes was observed. This work contributes to the broader adoption of mechanical treatments for removing residual metallic Al from weathered MSWI bottom ash and facilitates the application of treated ash as SCM.

Magnetoresistance properties in nickel-catalyzed, air-stable, uniform, and transfer-free graphene.

A transfer-free graphene with high magnetoresistance (MR) and air stability has been synthesized using nickel-catalyzed atmospheric pressure chemical vapor deposition. The Raman spectrum and Raman mapping reveal the monolayer structure of the transfer-free graphene, which has low defect density, high uniformity, and high coverage (>90%). The temperature-dependent (from 5 to 300 K) current-voltage (I-V) and resistance measurements are performed, showing the semiconductor properties of the transfer-free graphene. Moreover, the MR of the transfer-free graphene has been measured over a wide temperature range (5-300 K) under a magnetic field of 0 to 1 T. As a result of the Lorentz force dominating above 30 K, the transfer-free graphene exhibits positive MR values, reaching ∼8.7% at 300 K under a magnetic field (1 Tesla). On the other hand, MR values are negative below 30 K due to the predominance of the weak localization effect. Furthermore, the temperature-dependent MR values of transfer-free graphene are almost identical with and without a vacuum annealing process, indicating that there are low density of defects and impurities after graphene fabrication processes so as to apply in air-stable sensor applications. This study opens avenues to develop 2D nanomaterial-based sensors for commercial applications in future devices.

The status of binocular visual functions among Taiwan high-tech industry engineers and its correlation with computer vision symptom.

To analyze the status of binocular visual functions, the relationship between binocular visual function and computer vision-related symptoms in the high-tech industry group. The study sample was comprised of 33 participants aged between 20 and 40 years of age. After completing basic information and the Computer Vision Symptom Scale (CVSS-17) questionnaire, the participants underwent a comprehensive examination of binocular visual function. All data were statistically analyzed with SPSS V26.0 software. The value of the binocular vision function of the Taiwan high-tech industry group was significantly different compared with the Scheiman and Morgan standard value. Study subjects were generally found to exhibit larger exophoric at distance, which in turn might lead to a lower ability to maintain binocular fusion to a single image, or recover from fusional disruption at distance. Subjects also experienced accommodation and convergence problems at near at the same time. Age, gender, and refractive errors had no significant impact on CVSS-17 scores, only the duration of computer usage showed a significant effect, particularly for internal symptom factor (ISF) dimensions. In addition, the interaction between the ISF and external symptom factor resulted in more severe visual symptoms. Long-term use of electronic devices may lead to an imbalance in binocular vision function, thereby increasing or exacerbating visual symptoms. If the use of electronic devices is an unchangeable trend, interventions in prescription, visual training or the visual design of electronic products become worthwhile topics for development.

The anti-inflammatory effects of mesenchymal stem cells attenuate diffuse pulmonary hemorrhage.

There are few effective treatment options for diffuse pulmonary hemorrhage (DPH). We aimed to elucidate the therapeutic role and underlying mechanisms of mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) in DPH. Therapeutic effects of MSCs/MSC-EVs in pristane-induced DPH mice were evaluated via pulmonary function testing and histopathology. Transcriptome sequencing analyzed differentially expressed genes in control, DPH, and MSC groups. The proportion of macrophage polarization was evaluated in vivo and in vitro via fluorescence-activated cell sorting in control, DPH, MSC, MSC-EV inhalation, and MSC-EV intravenous groups. Intraperitoneal injection of pristane induced diffuse alveolar hemorrhage, early fibrosis, and inflammation in C57BL/6 mice. Monocytes were depleted in the peripheral blood in DPH mice and MSCs were recruited to the lungs, resulting in significantly attenuated diffuse alveolar hemorrhage and suppressed immunological response. This was more effective in the hyperacute hemorrhage phase than the early inflammatory phase. An MSC treatment-mediated anti-inflammatory effect was observed in DPH mice. Furthermore, MSC-EVs inhalation or tail-vein injection could effectively reduce DPH injury. MSCs could suppress macrophage M1 polarization in DPH in vivo and in vitro. MSCs displayed significant therapeutic effects in pristane-induced DPH, which may be a promising cell-free therapeutic approach.

On a framework of data assimilation for hyperparameter estimation of spiking neuronal networks.

When handling real-world data modeled by a complex network dynamical system, the number of the parameters is often much more than the size of the data. Therefore, in many cases, it is impossible to estimate these parameters and the exact value of each parameter is frequently less interesting than the distribution of the parameters. In this paper, we aim to estimate the distribution of the parameters in the mesoscopic neuronal network model from the macroscopic experimental data, for example, the BOLD (blood oxygen level dependent) signal. Herein, we assume that the parameters of the neurons and synapses are inhomogeneous but independently and identically distributed from certain distributions with unknown hyperparameters. Thus, we estimate these hyperparameters of the distributions of the parameters, instead of estimating the parameters themselves. We formulate this problem under the framework of data assimilation and hierarchical Bayesian method and present an efficient method named Hierarchical Data Assimilation (HDA) to conduct the statistical inference on the neuronal network model with the BOLD signal data simulated by the hemodynamic model. We consider the Leaky Integral-Fire (LIF) neuronal networks with four synapses and show that the proposed algorithm can estimate the BOLD signals and the hyperparameters with high preciseness. In addition, we discuss the influence on the performance of the algorithm configuration and the LIF network model setup.

Improvement of gelation properties of Penaeus vannamei surimi by magnetic field-assisted freezing in combination with curdlan.

Traditional methods of freezing and thawing may harm the quality of meat products. In order to reduce the negative impact of freezing on surimi products, the magnetic field-assisted freezing method is combined with various curdlan ratios to enhance the gelation characteristics of Penaeus vannamei surimi in this study. The results showed that the magnetic field-assisted freezing technique significantly improved the quality of thawed surimi compared with soaking freezing (SF), whereas the addition of curdlan further improved the gelation properties, and the gel strength, water-holding capacity, textural properties, whiteness, and G' value were significantly improved when its content was increased to 0.6 %. However, excessive amounts of curdlan interfered with protein covalent cross-linking, leading to a decrease in gel quality. Additionally, the addition of magnetic field and curdlan encouraged the shift of the α-helix to the random coil and ß-sheet transition, which stimulated the growth of myofibril molecules, exposed the hydrophobic groups and thiols, improved protein-molecule interactions, and promoted systematic gathering of proteins, leading to the formation of the microstructure of dense and small pores. It also resulted in a drop in water release, an increase in the proton density and a shift in the water condition from free water to more immobile water, which had higher sensory qualities. These effects together resulted in a reduction in thawing and cooking loss to 11.41 % and 13.83 %, respectively. These results also help to clarify the gelation process of shrimp surimi and help to regulate the gelation characteristics of shrimp surimi products.

The m6A reader IGF2BP3 preserves NOTCH3 mRNA stability to sustain Notch3 signaling and promote tumor metastasis in nasopharyngeal carcinoma.

Metastasis remains the major cause of treatment failure in patients with nasopharyngeal carcinoma (NPC), in which sustained activation of the Notch signaling plays a critical role. N6-Methyladenosine (m6A)-mediated post-transcriptional regulation is involved in fine-tuning the Notch signaling output; however, the post-transcriptional mechanisms underlying NPC metastasis remain poorly understood. In the present study, we report that insulin-like growth factor 2 mRNA-binding proteins 3 (IGF2BP3) serves as a key m6A reader in NPC. IGF2BP3 expression was significantly upregulated in metastatic NPC and correlated with poor prognosis in patients with NPC. IGF2BP3 overexpression promoted, while IGF2BP3 downregulation inhibited tumor metastasis and the stemness phenotype of NPC cells in vitro and in vivo. Mechanistically, IGF2BP3 maintains NOTCH3 mRNA stability via suppression of CCR4-NOT complex-mediated deadenylation in an m6A-dependent manner, which sustains Notch3 signaling activation and increases the transcription of stemness-associated downstream genes, eventually promoting tumor metastasis. Our findings highlight the pro-metastatic function of the IGF2BP3/Notch3 axis and revealed the precise role of IGF2BP3 in post-transcriptional regulation of NOTCH3, suggesting IGF2BP3 as a novel prognostic biomarker and potential therapeutic target in NPC metastasis.

Effects of laparoscopic and choledochoscopic gallbladder-preserving cholecystolithotomy on levels of operation indicators, gallbladder function, and cholecystokinin type-A receptor in patients with gallstones.

Introduction: Gallstones are a common digestive system disease. Aim: To assess the effects of laparoscopic and choledochoscopic gallbladder-preserving cholecystolithotomy on the levels of operation indicators, gallbladder function, and cholecystokinin type-A receptor (CCKAR) in patients with gallstones. Material and methods: The medical records of 100 patients with gallstones receiving operation from July 2019 to August 2022 were collected for retrospective analysis. They were divided into a laparoscopic group (n = 48) and a laparoscopic + choledochoscopic group (n = 52). The laparoscopic group received totally laparoscopic cholecystolithotomy, while the laparoscopic + choledochoscopic group underwent laparoscopic and choledochoscopic cholecystolithotomy. Their perioperative indicators, gallbladder function, stress indicators (cortisol (Cor), norepinephrine (NE), and C-reactive protein (CRP)), serum biochemical indicators (liver receptor homologue 1 (LRH-1), CCKAR, and vasoactive intestinal peptide (VIP)), and complications were compared. Results: The fasting gallbladder volume and gallbladder contraction rate increased, and the minimum residual volume and gallbladder wall thickness decreased in the laparoscopic + choledochoscopic group in comparison with those of the laparoscopic group 6 months after operation (p < 0.05). The levels of serum Cor, NE, CRP, and CCKAR were elevated, whereas the levels of serum LRH-1 and VIP were lowered in both groups 3 d after operation compared with those before operation (p < 0.05). The levels of serum Cor, NE, CRP, LRH-1, and VIP were lower, and the level of serum CCKAR was higher in the laparoscopic + choledochoscopic group than those in the laparoscopic group 3 d after operation (p < 0.05). Conclusions: Both laparoscopic gallbladder-preserving cholecystolithotomy and laparoscopic and choledochoscopic cholecystolithotomy are effective for treating gallstones. However, the latter combination method is superior in enhancing postoperative gallbladder function, decreasing the recurrence risk, regulating the expressions of LRH-1, CCKAR, and VIP, and promoting the postoperative recovery of gastrointestinal function.

Drug design education in China.

With the emergence of innovative technologies, including combinatorial chemistry, high-throughput screening, computer-aided drug design (CADD), artificial intelligence (AI) and big data, the importance of drug design in the field of drug discovery and development is increasing. Additionally, education in drug design plays an important role in the training of pharmaceutical talent. Starting with undergraduates, cultivating pharmaceutical design thinking, developing innovation and creativity, and establishing an interdisciplinary knowledge system will not only provide students with a solid knowledge basis but also promote the development of the pharmaceutical industry in China. This article presents the current status of pharmaceutical education and the distribution of drug design courses in China and summarizes the employment prospects of graduates, thus providing valuable references and evidence for global pharmaceutical design education.

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Since December 2019, coronavirus disease 2019 (COVID-19) has been rapidly spreading worldwide and affecting the physical and mental health of the general population. It may have even more serious potential harm to children with autism spectrum disorder (ASD). This paper provides a literature review on the psychological and behavioral problems experienced by children with ASD during the COVID-19 epidemic, as well as the factors influencing these issues. The findings of this review can serve as a basis for clinical research on ASD children.

Effect of к-carrageenan on saltiness perception and texture characteristic related to salt release in low-salt surimi.

The purpose of this study was to investigate the effect of Kappa (к)-carrageenan on texture and perception of saltiness of low salt surimi. The low-field nuclear magnetic resonance (LF-NMR) and microstructure results showed that к-carrageenan could promote the formation of more immobilized water in low salt surimi gel, change its matrix structure, and lead to the uneven spatial distribution of sodium, thus enhancing saltiness perception. The rheological properties of surimi showed that к-carrageenan could increase the network strength of low salt surimi gel and improve its thermostability. Furthermore, the low salt surimi gel added with к-carrageenan has lower cooking loss, higher water holding capacity (WHC), gel strength and improved texture properties. Therefore, к-carrageenan has the effects of improving the quality and increasing salt perception of surimi gel. This study provides a new method for reducing salt consumption in food industry.

Lysosomal cyst(e)ine storage potentiates tolerance to oxidative stress in cancer cells.

Cyst(e)ine is a key precursor for the synthesis of glutathione (GSH), which protects cancer cells from oxidative stress. Cyst(e)ine is stored in lysosomes, but its role in redox regulation is unclear. Here, we show that breast cancer cells upregulate major facilitator superfamily domain containing 12 (MFSD12) to increase lysosomal cyst(e)ine storage, which is released by cystinosin (CTNS) to maintain GSH levels and buffer oxidative stress. We find that mTORC1 regulates MFSD12 by directly phosphorylating residue T254, while mTORC1 inhibition enhances lysosome acidification that activates CTNS. This switch modulates lysosomal cyst(e)ine levels in response to oxidative stress, fine-tuning redox homeostasis to enhance cell fitness. MFSD12-T254A mutant inhibits MFSD12 function and suppresses tumor progression. Moreover, MFSD12 overexpression correlates with poor neoadjuvant chemotherapy response and prognosis in breast cancer patients. Our findings reveal the critical role of lysosomal cyst(e)ine storage in adaptive redox homeostasis and suggest that MFSD12 is a potential therapeutic target.