CONSTITUTIVE EXPRESSER OF PATHOGENESIS-RELATED GENES 5 is an RNA-binding protein controlling plant immunity via an RNA processing complex.

Plant innate immunity is capable of combating diverse and ever evolving pathogens. The plasticity of innate immunity could be boosted by RNA processing. Arabidopsis thaliana CONSTITUTIVE EXPRESSER OF PATHOGENESIS-RELATED GENES 5 (CPR5), a key negative immune regulator, is a component of the nuclear pore complex. Here we further identified CPR5 as a component of RNA processing complexes. Through genetic screening, we found that RNA splicing activator NineTeen Complex and RNA polyadenylation factor CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR, coordinately function downstream of CPR5 to activate plant immunity. CPR5 and these two regulators form a complex that is localized in nuclear speckles, an RNA processing organelle. Intriguingly, we found that CPR5 is an RNA-binding protein belonging to the Transformer 2 (Tra2) subfamily of the serine/arginine-rich family. The RNA recognition motif of CPR5 protein binds the Tra2-targeted RNA sequence in vitro and is functionally replaceable by those of Tra2 subfamily proteins. In planta, it binds RNAs of CPR5-regulated alternatively spliced genes (ASGs) identified by RNA-seq. ARGONAUTE 1 (AGO1) is one of the ASGs and, consistent with this, the ago1 mutant suppresses the cpr5 phenotype. These findings reveal that CPR5 is an RNA-binding protein linking RNA processing with plant immunity.

The biosynthesis of storage reserves and auxin is coordinated by a hierarchical regulatory network in maize endosperm.

Grain filling in maize (Zea mays) is intricately linked to cell development, involving the regulation of genes responsible for the biosynthesis of storage reserves (starch, proteins, and lipids) and phytohormones. However, the regulatory network coordinating these biological functions remains unclear. In this study, we identified 1744 high-confidence target genes co-regulated by the transcription factors (TFs) ZmNAC128 and ZmNAC130 (ZmNAC128/130) through chromatin immunoprecipitation sequencing coupled with RNA-seq analysis in the zmnac128/130 loss-of-function mutants. We further constructed a hierarchical regulatory network using DNA affinity purification sequencing analysis of downstream TFs regulated by ZmNAC128/130. In addition to target genes involved in the biosynthesis of starch and zeins, we discovered novel target genes of ZmNAC128/130 involved in the biosynthesis of lipids and indole-3-acetic acid (IAA). Consistently, the number of oil bodies, as well as the contents of triacylglycerol, and IAA were significantly reduced in zmnac128/130. The hierarchical regulatory network centered by ZmNAC128/130 revealed a significant overlap between the direct target genes of ZmNAC128/130 and their downstream TFs, particularly in regulating the biosynthesis of storage reserves and IAA. Our results indicated that the biosynthesis of storage reserves and IAA is coordinated by a multi-TFs hierarchical regulatory network in maize endosperm.

A Sequence-Indexed Mutator Insertional Library for Maize Functional Genomics Study.

Sequence-indexed insertional libraries are important resources for functional gene study in model plants. However, the maize (Zea mays) UniformMu library covers only 36% of the annotated maize genes. Here, we generated a new sequence-indexed maize Mutator insertional library named ChinaMu through high-throughput sequencing of enriched Mu-tagged sequences. A total of 2,581 Mu F2 lines were analyzed, and 311,924 nonredundant Mu insertion sites were obtained. Based on experimental validation, ChinaMu contains about 97,000 germinal Mu insertions, about twice as many as UniformMu. About two-thirds (66,565) of the insertions are high-quality germinal insertions (positive rate > 90%), 89.6% of which are located in genic regions. Furthermore, 45.7% (20,244) of the 44,300 annotated maize genes are effectively tagged and about two-thirds (13,425) of these genes harbor multiple insertions. We tested the utility of ChinaMu using pentatricopeptide repeat (PPR) genes. For published PPR genes with defective kernel phenotypes, 17 out of 20 were tagged, 11 of which had the previously reported mutant phenotype. For 16 unstudied PPR genes with both Mu insertions and defective kernel phenotypes, 6 contained insertions that cosegregated with the mutant phenotype. Our sequence-indexed Mu insertional library provides an important resource for functional genomics study in maize.

A conveniently synthesized Pt (IV) conjugated alginate nanoparticle with ligand self-shielded property for targeting treatment of hepatic carcinoma.

The clinical translation remains a major challenge for platinum drug loaded nanoparticle due to the complexity of composition and preparation. Here we employed only three ingredients to prepare Pt (IV) prodrug-loaded ligand-induced self-assembled nanoparticles (GA-ALG@Pt NPs) via facile one-pot route for liver tumor treatment. GA-ALG@Pt NPs were found equipped with intelligently ligand self-shielded property in which the internal GA could be induced to expose by initial cellular recognition, resulting in strengthened cellular uptake (20%-30%) and prolonged blood circulation time (3.43 times). Appreciable tumor targeting ability (2 times) and especially tumor selectivity (2.5 times) were obtained. Glutathione-triggered release of therapeutic agent generated satisfactory antitumor effect. Bio-safety is also a distinguishing feature of GA-ALG@Pt NPs that greatly relief the nephrotoxicity and systematic toxicity of cisplatin. This conveniently synthesized nanoparticle processes superior targeting capacity and biosecurity, supplying an effective approach to translational cancer therapy in the future.

Intraoperative electrocorticography-guided microsurgical management for patients with onset of supratentorial neoplasms manifesting as epilepsy: a review of 65 cases.

AIM: We reviewed the surgical procedures guided by intraoperative electrocorticography and outcome of 65 patients with onset of supratentorial neoplasms manifesting as epilepsy. METHOD: Clinical data were obtained for 65 patients with supratentorial neoplasms who received surgery, with the aid of intraoperative electrocorticography to screen epileptogenic foci before and after removal of neoplasms, and depth electrodes when needed. According to electrocorticography findings, appropriate surgical procedures were performed to treat the epileptogenic foci. In the control group, 72 patients received simple lesionectomy. Postoperative seizure outcomes were documented and analysed retrospectively. RESULTS: In the case group, 33 patients received lesionectomy only, while the other 32 patients underwent intraoperative electrocorticography-guided tailored epilepsy surgery. In total, 57 patients (87.7%) in the case group and 38 patients (52.8%) in the control group were seizure-free (Engel Class I). Comparing outcomes of patients with temporal lesions between the two groups, 80.0% patients (12/15) in the case group and 20.0% (3/15) in the control group were seizure-free. Furthermore, comparing the seizure outcomes of patients who finally underwent tailored epilepsy surgery and simple lesionectomy (33 after electrocorticography and 72 without electrocorticography), intraoperative electrocorticography-guided tailored epilepsy surgery demonstrated superiority over lesionectomy (Engel Class I; 87.5% vs. 63.8%, respectively). CONCLUSIONS: Electrocorticography plays an important role in the localisation of epileptogenic foci and evaluation of the effects of microsurgical procedures intraoperatively. Isolated lesionectomy is not usually sufficient for better postoperative seizure outcome. In addition, for patients with temporal tumours, especially in the non-dominant hemisphere, a more aggressive strategy, such as an anterior temporal lobectomy, is recommended.

Comparison of combined intravenous and inhalation anesthesia and total intravenous anesthesia in laparoscopic surgery and the identification of predictive factors influencing the delayed recovery of neurocognitive function.

Background: Compare the anesthesia effects of combined intravenous and inhalation anesthesia (CIVIA) and total intravenous anesthesia (TIVA) in laparoscopic surgery. Furthermore, our objective is to examine the elements that contribute to the delay in postoperative recovery of neurocognitive function and anticipate the manifestation of delayed recovery by analyzing serum cytokines. Methods: The CIVIA group and the TIVA group both consisted of 130 patients who were scheduled to have elective major abdominal surgery through laparoscopy. The criteria taken into account by the observational and record-keeping study were the patients' ages, sexes, body masses, heights, and the presence or absence of any preexisting problems. Both groups also had their anesthetic depth, duration, and per-unit-of-time muscle relaxant and analgesic dosages recorded. Finally, the length of each patient's stay in the hospital as well as their overall length of stay were tracked. By using the Mini-Mental State Examination (MMSE) to measure cognitive function, we assessed the mental states of the subjects. Additionally, we wanted to identify any biomarkers that could be linked to postoperative cognitive decline or delays in neurocognitive recovery. Results: A total of 51 participants from the CIVIA group and 53 participants from the TIVA group satisfactorily completed the necessary neuropsychological exam for identifying delayed neurocognitive recovery at the study's completion. In the initial data of the two groups, no significant discrepancies were found (p > 0.05). The CIVIA group exhibited noteworthy reductions in the quantity of administered analgesics and muscle relaxants per unit of time in comparison to the TIVA group (p < 0.05). In addition to this, the duration from the sevoflurane tank being closed to the extubation period demonstrated a significant reduction in the CIVIA group compared to the TIVA group (p < 0.05). Moreover, no statistically notable distinction was observed in terms of postoperative hospitalization duration and overall hospitalization duration among both groups (p > 0.05). According to the study, both the CIVIA group and the TIVA group had a total of 7 (13.72%) and 17 (32.07%) individuals, respectively, who met the criteria for neurocognitive delayed recovery (Odds Ratio: 0.336; 95% CI: 0.134-0.864; p = 0.026). According to the research findings, it is indicated that there is a possibility for an increased presence of IL-6 in the bloodstream within 60 min following the incision made on the skin. This occurrence subsequently leads to the prolonged restoration of neurocognitive capabilities. Conclusion: The CIVIA technique outperforms the TIVA method in terms of overall assessment in the setting of laparoscopic surgery. It's also important to remember that an increased blood IL-6 level during laparoscopy may operate as a separate risk factor for a delay in the restoration of neurocognitive function.

ß-Sitosterol Inhibits Tumor Growth and Amplifies Rituximab Sensitivity through Acid Sphingomyelinase/Ceramide Signaling in Diffuse Large B-Cell Lymphoma.

Rituximab (RTX) resistance is a notable challenge in treating diffuse large B-cell lymphoma (DLBCL). ß-Sitosterol (ß-ST) is a plant sterol that has been found in a broad variety of fruits, spices, and medicinal plants. The antineoplastic properties of ß-ST are established in various solid malignancies; however, its effect on DLBCL is uncharted. This study investigates the role of ß-ST in DLBCL as well as the underlying mechanisms. Our findings indicated that ß-ST impeded DLBCL cell proliferation in a concentration- and time-dependent manner. ß-ST appeared to alter sphingolipid metabolism, facilitate acid sphingomyelinase (ASM) translocation to the plasma membrane, augment ceramide platforms through increased ceramide synthesis, and consequently induce apoptosis in DLBCL cells. Furthermore, we found that RTX initiated both apoptotic and survival pathways in vitro, with the former contingent on the transient activation of the ASM, and ß-ST could amplify the anti-DLBCL efficacy of RTX by modulating ASM/Ceramide (Cer) signaling. Collectively, our findings elucidate the mechanistic role of ß-ST in DLBCL and underscore its potential in amplifying the antineoplastic efficacy of RTX via ASM activation, proposing a potential avenue to improve the efficacy of RTX therapy.

Facile Fabrication of Anthocyanin-Nanocellulose Hydrogel Indicator Label for Intelligent Evaluation of Minced Pork Freshness.

In order to develop a reliable and rapid method for meat freshness detection, nanocellulose (TOCNF) prepared via the TEMPO (2,2,6,6-tetramethylpiperidine oxidation) oxidation method was used as raw material to prepare hydrogels using Zn2+ coordination and binding. Physicochemical properties such as water absorption and porosity were analyzed. It was further used to select suitable hydrogels for the preparation of indication labels after anthocyanin adsorption, and it was applied in the freshness detection of fresh minced pork. Five percent TOCNF (w/w) aqueous solution was homogenized by high shear for 4 min, and 20% (w/w) zinc chloride solution was added to it, so that the concentration of zinc ions could reach 0.25 mol/L. After standing for 24 h, the hydrogel was obtained with good water absorption and a porous three-dimensional network structure. The activation energies of volatile base nitrogen (TVBN) and anthocyanin indicating label color changes were 59.231 kJ/mol and 69.453 kJ/mol, respectively. The difference between the two is within 25 kJ/mol, so the prepared indicator label can accurately visualize the shelf life of fresh pork.

The roles of ERIANIN in tumor and innate immunity and its' perspectives in immunotherapy.

Traditional Chinese medicine has been used in China for thousands of years. In 2022, the 14th Five-Year Plan for the Development of Traditional Chinese Medicine was released, aiming to enhance traditional Chinese medicine health services and improve policies and systems for high-quality traditional Chinese medicinal development by 2025. ERIANIN, the main component of the traditional Chinese medicine Dendrobium, plays an important role in anti-inflammatory, antiviral, antitumor, antiangiogenic, and other pharmacological effects. ERIANIN has broad-spectrum antitumor effects, and its tumor-suppressive effects have been confirmed in the study of various diseases, such as precancerous lesions of the stomach, gastric cancer, liver cancer, lung cancer, prostate cancer, bladder cancer, breast cancer, cervical cancer, osteosarcoma, colorectal cancer, leukaemia, nasopharyngeal cancer and melanoma through the multiple signaling pathways. Thus, the aim of this review was to systematically summarise the research on ERIANIN with the aim of serving as a reference for future research on this compound and briefly discuss some future perspectives development of ERIANIN in combined immunotherapy.

Lobar or sublobar resection for early-stage second primary lung cancer ≤ 3 cm in size: a SEER population-based study.

PURPOSE: Surgical strategy for second primary lung cancer (SPLC) may be more conservative due to influence of first primary lung cancer (FPLC). The optimal surgical method for SPLC warrants discussion. We aimed to explore a more suitable surgical approach for early-stage (T1-T2N0, ≤ 3 cm) SPLC and provide insights for clinical practice. METHODS: A retrospective study was conducted using data from the Surveillance, Epidemiology and End Results database between 2004 and 2018, and data of patients with early-stage SPLC who underwent secondary surgery were collected. Propensity score matching (PSM) reduced potential bias between lobar and sublobar resection groups. The effect of lobar and sublobar resection on overall survival (OS) was assessed in all patients and subgroups. RESULTS: A total of 714 patients who met the study entry criteria were enrolled, including 476 patients in the sublobar resection group (66.67%) and 238 patients in the lobar resection group (33.33%). There was no difference in OS between the lobar and sublobar resection groups before and after PSM (P = 0.289) and (P = 0.608), respectively. Subgroup analyses showed that lobar resection achieved a significantly better OS than sublobar resection only in patients with an SPLC tumor size of 2-3 cm (P < 0.05). CONCLUSION: The OS of sublobar resection was not significantly different from that of lobar resection for early-stage SPLC. For SPLC with a 2-3 cm tumor size, lobar resection is more advantageous than sublobar resection.

Prognostic prediction of BRAF(V600E) and its relationship with sodium iodide symporter in classic variant of papillary thyroid carcinomas.

BACKGROUND: The aim of this study was to evaluate the prognosis of the classic variant of papillary thyroid carcinomas with the BRAF(V600E) mutation and 131I treatment failure in those tumors due to lower functional sodium iodide symporter expression. METHODS: 109 papillary thyroid carcinomas were associated with clinicopathologic features. The BRAF(V600E) mutation was evaluated by direct sequencing and sodium iodide symporter protein was determined by immunohistochemistry. RESULTS: We found that the BRAF(V600E) mutation was significantly associated with the classic variant of papillary thyroid carcinomas and was independent of tumor size, the presence of extrathyroid invasion and lymph node metastasis, advanced TMN stages, and a high risk of disease recurrence. Moreover, the BRAF(V600E) mutation was associated with a statistically significant lower functional NIS protein expression in the classic variant of papillary thyroid carcinomas. However, those statistically significant relationships were not found in the follicular variant of papillary thyroid carcinomas. CONCLUSIONS: The BRAF(V600E) mutation might be associated with a more aggressive phenotype and a poor prognosis, causing less NIS-mediated 131I uptake due to a lower functional NIS protein expression in the classic variant of papillary thyroid carcinomas. Our current study appears to be valuable for predicting prognosis and is of important clinical significance for surgery and 131I treatment in patients with the classic variant of papillary thyroid carcinomas.

Effect of glutamic acid on the preparation and characterization of Pickering emulsions stabilized by zein.

In this study, glutamic acid and zein were utilized to prepare colloidal nanoparticles as stabilizers for Pickering emulsions. The effect of the ratio of glutamic acid to zein on the stability, zeta potential, particle size, morphology, and structure of colloidal nanoparticles was studied. The results showed that zein and glutamic acid combined in the form of noncovalent bonds, which changed the characteristics of the zein. In addition, colloidal particles aggregation was induced by glutamic acid, which altered the distribution of droplets in the emulsion, and increased the adsorption of proteins on the surface of the oil droplets, as reflected by the analysis of the size, microstructure, rheological behaviours, and driving force of the Pickering emulsion. Hydrophobic interactions and electrostatic interactions were the main driving forces for the formation of colloidal particles, which was determined by driving force analysis and the change of the zeta potential.

Improvement of Storage Stability of Zein-Based Pickering Emulsions by the Combination of Konjac Glucomannan and L-Lysine.

In this work, L-lysine (Lys) was employed together with konjac glucomannan (KGM) to fabricate zein colloidal particles (ZCPs) aimed at enhancing the storage stability of Pickering emulsions. With the addition of Lys, zein-Lys colloidal particles (ZLCPs) and zein-Lys-KGM (ZLKCPs) exhibited smaller particle size (133.64 ± 1.43, 162.54 ± 3.51 nm), polydispersity index (PDI) (0.10 ± 0.029, 0.13 ± 0.022), π value, and more adsorbed protein. Meanwhile, KGM underwent deamidation in an alkaline solution, so the emulsions stabilized by ZLKCPs exhibited a solid gel-like structure with higher storage modulus (G') and loss modulus (G''), leading to lower fluidity and better stability. The synergistic effects of Lys and KGM improved the stability of the emulsion. Hydrophobic interactions and hydrogen bonds were the main driving forces forming colloidal particles, which were determined by driving force analysis.

Mechanism of low-salt surimi gelation induced by microwave heating combined with l-arginine and transglutaminase: On the basis of molecular docking between l-arginine and myosin heavy chain.

The reduction of the salt content of foods is of interest for health reasons. The present study showed that low-salt surimi gels could be produced using a combination of l-arginine (Arg) and transglutaminase (TGase) under microwave (MW) irradiation. The low-salt surimi gels produced by MW had similar physicochemical properties as regular-salt surimi gels produced by conventional two-stage water bath heating. Compared to low-salt surimi gels containing TGase alone, Arg increased the water holding capacity and gel strength (P < 0.05) and promoted the formation of a more homogeneous and compact three-dimensional gel network. As a result, there was a significant increase in the proportion of immobilized water and decrease in the proportion of free water (P < 0.05). The nature of the binding sites between Arg and myosin heavy chain was predicted using the molecular docking simulations analysis. These results may be useful for the development of low-salt surimi products.

Effect of nano-silica coating combined with pressurized Ar treatment on postharvest quality and reactive oxygen species metabolism in sweet cherry fruit.

The mechanisms of effect of nano-silica coating and pressurized Ar on regulating reactive oxygen species (ROS) generation and scavenging in the senescence of sweet cherries remains unclear. The amounts of reactive oxygen species, hydrogen peroxide, non-enzymatic antioxidants and antioxidases, and cell membrane lipid peroxidation in sweet cherries were determined. Nano-silica coating, pressurized Ar, and the combination of these two treatments, all significantly delayed senescence by suppressing decay rate, and maintained good sensory quality. In additional, all treatments inhibited the generation and accumulation of superoxide anion and hydrogen peroxide, and mitigated the lipid peroxidation of cell membranes of sweet cherries. The combination of these two treatments maintained higher contents of ascorbic acid and glutathione, and enhanced the activities of antioxidases in sweet cherries. It is suggested that nano-silica coating and pressure Ar mediated the ROS metabolism, which might have a role in retaining the quality sweet cherries during cold storage.

Novel Fabrication of Zein-Soluble Soybean Polysaccharide Nanocomposites Induced by Multifrequency Ultrasound, and Their Roles on Microstructure, Rheological Properties and Stability of Pickering Emulsions.

In this work, soluble soybean polysaccharides (SSPS) were employed together with multifrequency ultrasound to fabricate zein nanocomposites which were conducive to enhancing the stability of high internal phase emulsions (HIPEs). Compared with non-ultrasonic treated zein colloidal particle samples (132.23 ± 0.85 nm), the zein nanoparticles samples induced by dual-frequency ultrasound exhibited a smaller particle size (114.54 ± 0.23 nm). Furthermore, the particle size of the zein composite nanoparticles (256.5 ± 4.81) remarkably increased with SPSS coating, consequently leading to larger fluorescence intensity together with lower zeta-potential (-21.90 ± 0.46 mv) and surface hydrophobicity (4992.15 ± 37.28). Meanwhile, zein-SSPS composite nanoparticles induced by DFU showed remarkably enhanced thermal stability. Fourier transform infrared (FTIR) spectroscopy and Circular dichroism (CD) spectroscopy were also used to characterize zein-SSPS composite nanoparticles. The results confirmed that DFU combined with SSPS treatment significantly increased ß-sheets (from 12.60% ± 0.25 b to 21.53% ± 0.37 c) and reduced α-helix content (34.83% ± 0.71 b to 23.86% ± 0.66 a) remarkably. Notably, HIPEs prepared from zein-SSPS nanocomposites induced by dual-frequency simultaneous ultrasound (DFU) at 40/60 kHz showed better storage stability. HIPEs stabilized by DFU induced zein-SSPS nanoparticles exhibited higher storage modulus (G') and loss modulus (G″), leading to lower fluidity, together with better stability contributing to the water-binding capacity and three-dimensional (3D) network structure of the HIPEs emulsion. The findings of this study indicate that this method can be utilized and integrated to further extend the application of zein and SSPS and explore HIPEs.

Safety of chidamide plus rituximab in elderly patients with relapsed or refractory B-cell lymphoma in China: a multicenter, single-arm, phase II study.

BACKGROUND: Patients over 65 years old with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) relapse or being refractory to rituximab-associated chemotherapy have limited treatment options. Chidamide has the ability to enhance the sensitivity of rituximab-resistant tumors in vivo has been confirmed. We aimed to assess the activity and safety profile of chidamide plus rituximab in elderly Chinese patients with recurrent or refractory B-cell lymphoma. METHODS: In this prospective, single-arm phase II trial, we enrolled patients from three hospitals in China with histopathological diagnoses of DLBCL and FL who had relapsed or were refractory to previous lines of rituximab-associated chemotherapy. Patients were given chidamide (10 mg on days 1-6 and 8-14) and rituximab (375 mg/m2 on day 7). The treatments were repeated every 21 days. The primary endpoint was the objective response rate (ORR). The secondary endpoints included the disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Thirteen patients were enrolled and commenced treatment between November 12, 2018, and December 24, 2020. As of March 20, 2021, two patients (15.4%) were still receiving treatment. The median follow-up was 13.4 months. The ORR was 40% for the DLBCL cohort (n=10), and 100% for the FL cohort (n=3). DLBCL patients had a median PFS (mPFS) of 2.6 months (0.9-31.2 months) and a median OS (mOS) of 16.7 months (2.3-13.6 months). Neither mPFS nor mOS was reached in the FL cohort. The most frequent treatment-related adverse events (TRAEs) were leukopenia (38.5%), neutropenia (30.8%), lymphopenia (30.8%), thrombocytopenia (30.8%), fatigue (38.5%), and hyperuricemia (30.8%). CONCLUSIONS: Chidamide plus rituximab is clinically effective with an acceptable toxicity profile in elderly patients over 65 years old with relapsed or refractory DLBCL and FL. Further investigation is ongoing.

Use of l-arginine-assisted ultrasonic treatment to change the molecular and interfacial characteristics of fish myosin and enhance the physical stability of the emulsion.

The effects of l-arginine (Arg)-assisted ultrasonic treatment on the molecular and interfacial characteristics of myosin and emulsifying properties of the emulsion were evaluated to ascertain the underlying mechanism in improving the emulsion stability. Ultrasonication induced the exposure of residues of native myosin, which was increased by the addition of Arg (40 mM). Furthermore, in terms of emulsions containing Arg, the higher the ultrasonication intensity was, the greater the increase in adsorbed protein (from 15.43 ± 0.28% to 50.49 ± 1.65%) and π value, and the decrease in droplet sizes (from 4098 nm to 2324 nm) (P < 0.05). Moreover, the increase in the ordered structures of interfacial myosin induced by Arg and ultrasonication favoured the formation of a protein gelation network. In summary, Arg-assisted ultrasonic treatment improved the stability of the emulsion by inducing the exposure of native myosin and facilitating the formation of ordered structures of interfacial myosin.

A peptidic inhibitor for PD-1 palmitoylation targets its expression and functions.

Programmed cell death protein 1 (PD-1) is a crucial anticancer target, but the relatively low response rate and acquired resistance to existing antibody drugs highlight an urgent need to develop alternative targeting strategies. Here, we report the palmitoylation of PD-1, discover the main DHHC enzyme for this modification, reveal the mechanism of its effect on PD-1 protein stability, and rationally develop a peptide for targeting PD-1 expression. Palmitoylation promoted the trafficking of PD-1 to the recycling endosome, thus preventing its lysosome-dependent degradation. Palmitoylation of PD-1, but not of PD-L1, promoted mTOR signaling and tumor cell proliferation, and targeting palmitoylation displayed significant anti-tumor effects in a three-dimensional culture system. A peptide was designed to competitively inhibit PD-1 palmitoylation and expression, opening a new route for developing PD-1 inhibitors and combinatorial cancer immunotherapy.

Sevoflurane attenuates brain damage through inhibiting autophagy and apoptosis in cerebral ischemia­reperfusion rats.

The present study aimed to investigate the effects of sevoflurane post­conditioning in a rat brain cerebral ischemia­reperfusion (I/R) model and examine its possible mechanism. Rats were randomly divided into six groups: Sham control group (Sham), I/R group, sevoflurane group (Se), Toll­like receptor­4 (TLR4) inhibitor group (Tak­242), nuclear factor (NF)­κB inhibitor group (QNZ) and Sevoflurane post­conditioning combined with TLR4­NF­κB signaling pathway inhibitor group (Se + Tak­242). Morris water maze test and tetrazolium chloride staining were used to investigate the I/R injury. The nerve cell apoptosis and autophagy in cortical tissue were detected by TUNEL and transmission electron microscopy, respectively. The expression of TLR4 protein in cortical tissue was observed by immunohistochemical staining. The expression of autophagy and apoptotic associated proteins in cortical tissues and the activity of TLR4­NF­κB signaling pathway were assayed by western blot analysis. Sevoflurane post­conditioning improved the learning and memory dysfunction caused by cerebral I/R injury. The cerebral infarction area, nerve cell apoptosis and formation of autophagic vacuoles were reduced after sevoflurane administration. The expression of light chain 3II/I, Beclin­1, Bad and Cleaved­Caspase­3 proteins were inhibited and the expression of Bcl­2 protein was upregulated after sevoflurane administration. Sevoflurane post­conditioning also inhibited the TLR4 protein and NF­κB phosphorylation, and increased inhibitor of kBα phosphorylation. The treatment effect of Tak­242 and QNZ groups were not significantly different compared with the Se group (P>0.05), and the Se + Tak­242 group had the best results. The present study demonstrated that sevoflurane post­conditioning could protect middle cerebral artery occlusion­induced brain injury rats by inhibiting autophagy and apoptosis, and that its mechanism is related to the TLR4­NF­κB signaling pathway.