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Objective To observe the injury of intestinal mucosal barrier and the expression of autophagy protein in colon tissue of rats with chronic renal failure. Methods Thirty SPF healthy male SD rats were randomly divided into sham operation group (10 rats) and model group (20 rats). The model group was given adenine 200 mg/(kg·d) by gavage for 4 weeks after left nephrectomy. The general conditions of rats were observed. Serum, renal tissue and colon tissue samples were collected at 4 and 8 weeks after gavage. The levels of serum creatinine, urea nitrogen, TNF-α, IL-6 and LPS were measured by ELISA. Renal and colon tissue were examined by HE staining and microscopy. The protein expressions of LC3, beclin-1, ZO-1 and claudin-1 were detected by Western blot. Results Compared with the sham operation group, the model group rats gradually showed a slow response to external stimuli, slow action, withered and yellow hair color, dull luster, pale conjunctiva and slow weight gain. The levels of serum creatinine, urea nitrogen and inflammatory factors in the model group were all higher than those in the sham operation group, and increased at 8 weeks compared with 4 weeks (P＜0.05). Renal pathology in the model group showed renal tubular dilatation, lymphatic and monocyte infiltration, glomerulosclerosis and interstitial fibrosis. Histopathology of colon in model group showed atrophy and collapse of intestinal villi, infiltration of inflammatory cells in mucosal layer and aggravation of pathological changes, which was more serious at 8 weeks than at 4 weeks. The expression of LC3Ⅱ/Ⅰ, Beclin-1, ZO-1 and Claudin-1 in the model group decreased as compared to those of sham operation group(P＜0.05), and much decreased at 8 weeks as compared with 4 weeks (P＜0.05). Conclusions Autophagy disorder may be a potential mechanism causing intestinal mucosal barrier injury in rats with chronic renal failure.

[Display omitted] The nature of the zero-temperature phase diagram of the spin- 1 / 2 J 1 - J 2 Heisenberg model on a square lattice has been debated in the past three decades, and it remains one of the fundamental problems unsettled in the study of quantum many-body theory. By using the state-of-the-art tensor network method, specifically, the finite projected entangled pair state (PEPS) algorithm, to simulate the global phase diagram of the J 1 - J 2 Heisenberg model up to 24 × 24 sites, we provide very solid evidences to show that the nature of the intermediate nonmagnetic phase is a gapless quantum spin liquid (QSL), whose spin-spin and dimer-dimer correlations both decay with a power law behavior. There also exists a valence-bond solid (VBS) phase in a very narrow region 0.56 ≲ J 2 / J 1 ≤ 0.61 before the system enters the well known collinear antiferromagnetic phase. We stress that we make the first detailed comparison between the results of PEPS and the well-established density matrix renormalization group (DMRG) method through one-to-one direct benchmark for small system sizes, and thus give rise to a very solid PEPS calculation beyond DMRG. Our numerical evidences explicitly demonstrate the huge power of PEPS for highly frustrated spin systems. Finally, an effective field theory is also proposed to understand the physical nature of the discovered gapless QSL and its relation to deconfined quantum critical point (DQCP). [ABSTRACT FROM AUTHOR]

Epilepsy, which is caused by abnormal neuronal firing in the brain, is a common neurological disease and affects motor and cognitive functions. Excessive levels of glutamate and insufficient levels of inhibitory GABA are involved in its pathophysiology. Valproic acid (Val), a GABAergic agonist, is one of the first‐line antiepileptic drugs, but it shows many adverse side effects at the clinical dose. Clavulanic acid (CA), a β‐lactamase inhibitor, has been demonstrated to increase glutamate transporter‐1 expression. This study evaluated the effects of CA and Val in an epilepsy rat model. Male Wistar rats received intraperitoneal injections of pentylenetetrazol (PTZ, 35 mg/kg, every other day, IP, for 13 days) to induce kindling epilepsy. After four times of PTZ injection, rats received daily treatment with CA (1 or 10 mg/kg, IP), Val (50 or 100 mg/kg, IP), or the combination of CA (1 mg/kg) and Val (50 mg/kg) for 7 consecutive days. Motor, learning, and memory functions were measured. Rats with PTZ‐induced kindling exhibited seizures, motor dysfunction, cognitive impairment, and cell loss and reduction of neurogenesis in the hippocampus. Neither 1 mg/kg CA nor 50 mg/kg Val treatment was effective in alleviating behavioral and neuronal deficits. However, treatment with 10 mg/kg CA, 100 mg/kg Val, and the combination of 1 mg/kg CA and 50 mg/kg Val improved these behavioral and neuronal deficits. Particularly, the combination of CA and Val showed synergistic effects on seizure suppression, suggesting the potential for treating epilepsy and related neuronal damage and motor and cognitive deficits. [ABSTRACT FROM AUTHOR]

Postoperative breast cancer recurrence is tricky due to the limited therapeutic options. Transforming growth factors-β (TGF-β) is vital in promoting postoperative tumor recurrence. However, conventional blocking strategies fail to satisfy both bio-safety and sufficient relapse correction. Neutrophil extracellular traps (NETs) are essential for the spatiotemporal dynamics of TGF-β at tumor-resection sites, whose unique mechanism for local TGF-β amplification could remarkably increase the risk of relapse after surgery. Herein, the principle of NETs formation is ingeniously utilized to construct a surgical residual cavity hydrogel that mimics NETs formation. The hydrogel is prepared based on the electrostatic interaction between histidine (His) and sodium alginate (Alg). Then, arginine deiminase 4 (PAD4) protein is released during NETs formation. Simultaneously, the electrical property of His in hydrogel changes automatically, which further lead to promising localized release of anti-TGF-β. The hydrogel system can realize specific and selective drug release at targeted NETs site over a prolonged period while exhibiting excellent biocompatibility. Superior breast cancer recurrence inhibition is achieved by suppressing TGF-β and related indicators, impeding epithelial-mesenchymal transition (EMT) progression, and rectifying the locally exacerbated immunosuppressive environment within NETs. The novel NETs local microenvironment drug release functional hydrogel will provide inspiration for postoperative recurrence correction strategies., (© 2024 Wiley‐VCH GmbH.)

Motivated by the novel phenomena observed in the layered material SrCu_{2}(BO_{3})_{2}, the Shastry-Sutherland model (SSM) has been extensively studied as the minimal model for SrCu_{2}(BO_{3})_{2}. However, the nature of its quantum phase transition from the plaquette valence-bond solid to antiferromagnetic phase is under fierce debate, posing a challenge to understand the underlying quantum criticality. Via the state-of-the-art tensor network simulations, we study the ground state of the SSM on large-scale size up to 20×20 sites. We identify the continuous transition nature accompanied by an emergent O(4) symmetry between the plaquette valence-bond solid and antiferromagnetic phase, which strongly suggests a deconfined quantum critical point (DQCP). Furthermore, we map out the phase diagram of an extended SSM that can be continuously tuned to the SSM, which demonstrates the same DQCP phenomena along a whole critical line. Our results indicate a compelling scenario for understanding the origin of the proposed proximate DQCP in recent experiments of SrCu_{2}(BO_{3})_{2}.

Oils and fats are commonly used in the pharmaceutical industry as solvents, emulsifiers, wetting agents, and dispersants, and are an important category of pharmaceutical excipients. Fatty acids with unique compositions are important components of oil pharmaceutical excipients. The Chinese Pharmacopoeia provides clear descriptions of the fatty acid types and limits suitable for individual oil pharmaceutical excipient. An unqualified fatty acid composition or content may indicate adulteration or deterioration. The fatty acid composition, as a key indicator for the identification and adulteration evaluation of oil pharmaceutical excipients, can directly affect the quality and safety of oil pharmaceutical excipients and preparations. Gas chromatography is the most widely used technique for fatty acid analysis, but it generally requires derivatization, which affects quantitative accuracy. Supercritical fluid chromatography (SFC), an environmentally friendly technique with excellent separation capability, offers an efficient method for detecting fatty acids without derivatization. Unlike other chromatographic methods, SFC does not use nonvolatile solvents (e. g., water) as the mobile phase, rendering it compatible with an evaporative light-scattering detector (ELSD) for enhanced detection sensitivity. However, the fatty acids in oil pharmaceutical excipients exist in the free and bound forms, and the low content of free fatty acids in these oil pharmaceutical excipients not only poses challenges for their detection but also complicates the determination of characteristic fatty acid compositions and contents. Moreover, the compositions and ratios of fatty acids are influenced by environmental factors, leading to interconversion between their two forms. In this context, saponification provides a simpler and faster alternative to derivatization. Saponification degrades oils and fats by utilizing the reaction between esters and an alkaline solution, ultimately releasing the corresponding fatty acids. Because this method is more cost effective than derivatization, it is a suitable pretreatment method for the detection of fatty acids in oil pharmaceutical excipients using the SFC-ELSD approach. In this study, we employed SFC-ELSD to simultaneously determine six fatty acids, namely, myristic acid, palmitic acid, stearic acid, arachidic acid, docosanoic acid, and lignoceric acid, in oil pharmaceutical excipients. Saponification of the oil pharmaceutical excipients using sodium hydroxide methanol solution effectively avoided the bias in the determination of fatty acid species and contents caused by the interconversion of fatty acids and esters. The separation of the six fatty acids was achieved within 12 min, with good linearity within their respective mass concentration ranges. The limits of detection and quantification were 5-10 mg/L and 10-25 mg/L, respectively, and the spiked recoveries were 80.93%-111.66%. The method proved to be sensitive, reproducible, and stable, adequately meeting requirements for the analysis of fatty acids in oil pharmaceutical excipients. Finally, the analytical method was successfully applied to the determination of six fatty acids in five types of oil pharmaceutical excipients, namely, corn oil, soybean oil, coconut oil, olive oil, and peanut oil. It can be combined with principal component analysis to accurately differentiate different types of oil pharmaceutical excipients, providing technical support for the rapid identification and quality control of oil pharmaceutical excipients. Thus, the proposed method may potentially be applied to the analysis of complex systems adulterated with oil pharmaceutical excipients.

Objective: To investigate the mechanisms of Astragaloside Ⅳ on inhibiting apoptosis and delaying kidney aging in rats by regulating SIRT1/p53 signaling pathway., Methods: The aging model was established by subcutaneous injection of D-galactose 200 mg/(kg·d). SPF-grade healthy male SD rats were randomly divided into 4 groups: normal control group (intragastric infusion of 5 ml/(kg·d) normal saline), aging model group (intragastric infusion of 5 ml/(kg·d) normal saline), Astragaloside IV group (intragastric infusion of 40 mg/(kg·d) Astragaloside IV),and SRT1720 group( intragastric infusion of 20 mg/(kg·d) SRT1720), with 10 rats in each group. After 8 weeks, the serum samples of rats were collected to detect the levels of renal function (creatinine and urea nitrogen) and senescent associated secretory phenotype (TGF-β and IL-6) by ELISA. The renal tissues of rats were obtained for HE and Masson staining. The protein and mRNA expressions of SIRT1, p53, Bcl-2, Bax, p21 and pRb were detected by Western blot and RT-PCR., Results: Serum creatinine and urea nitrogen levels in the aging model group were higher than those in the normal group, but there was no significant difference in each group ( P ＞0.05). The serum levels of TGF-β and IL-6 in the aging model group were higher than those in the normal group ( P ＜0.05), and which in the Astragaloside IV group and SRT1720 group were lower than those in the model group ( P ＜0.05). There was no significant differences between Astragaloside IV group and SRT1720 group ( P ＞0.05). The results of pathological staining of renal tissues showed that, compared with the normal group, the renal tubules dilated, local atrophy, infiltration of inflammatory cells and proliferation of collagen fibers were observed in the aging model group. Compared with the aging model group, the pathological changes were alleviated in Astragaloside IV group and SRT1720 group. The results of Western blot and RT-PCR showed that, compared with the normal group, the protein and mRNA expressions of SIRT1 and pRb in the renal tissue of the aging group were decreased, the protein expression of Bcl-2 was decreased( P ＜0.05), and the protein and mRNA expressions of p53 and p21 were increased, the protein expression of Bax was increased( P ＜0.05). Compared with the aging group, Astragaloside IV and SRT1720 improved the above-mentioned indexes ( P ＜0.05)., Conclusion: Astragaloside IV can delay kidney aging by regulating the SIRT1/p53 signaling pathway.