Transferrin-conjugated magnetic nanoparticles for the isolation of brain-derived blood exosomal MicroRNAs: A novel approach for Parkinson's disease diagnosis.

BACKGROUND: Brain-derived exosomes circulate in the bloodstream and other bodily fluids, serving as potential indicators of neurological disease progression. These exosomes present a promising avenue for the early and precise diagnosis of neurodegenerative conditions. Notably, miRNAs found in plasma extracellular vesicles (EVs) offer distinct diagnostic benefits due to their stability, abundance, and resistance to breakdown. RESULTS: In this study, we introduce a method using transferrin conjugated magnetic nanoparticles (TMNs) to isolate these exosomes from the plasma of patients with neurological disorders. This TMNs technique is both quick (<35 min) and cost-effective, requiring no high-priced ingredients or elaborate equipment for EV extraction. Our method successfully isolated EVs from 33 human plasma samples, including those from patients with Parkinson's disease (PD), Multiple Sclerosis (MS), and Dementia. Using quantitative polymerase chain reaction (PCR) analysis, we evaluated the potential of 8 exosomal miRNA profiles as biomarker candidates. Six exosomal miRNA biomarkers (miR-195-5p, miR-495-3p, miR-23b-3P, miR-30c-2-3p, miR-323a-3p, and miR-27a-3p) were consistently linked with all stages of PD. SIGNIFICANCE: The TMNs method provides a practical, cost-efficient way to isolate EVs from biological samples, paving the way for non-invasive neurological diagnoses. Furthermore, the identified miRNA biomarkers in these exosomes may emerge as innovative tools for precise diagnosis in neurological disorders including PD.

A Wearable Thin-Film Hydrogel Laser for Functional Sensing on Skin.

Flexible photonics offers the possibility of realizing wearable sensors by bridging the advantages of flexible materials and photonic sensing elements. Recently, optical resonators have emerged as a tool to improve their oversensitivity by integrating with flexible photonic sensors. However, direct monitoring of multiple psychological information on human skin remains challenging due to the subtle biological signals and complex tissue interface. To tackle the current challenges, here, we developed a functional thin film laser formed by encapsulating liquid crystal droplet lasers in a flexible hydrogel for monitoring metabolites in human sweat (lactate, glucose, and urea). The three-dimensional cross-linked hydrophilic polymer serves as the adhesive layer to allow small molecules to penetrate from human tissue to generate strong light--matter interactions on the interface of whispering gallery modes resonators. Both the hydrogel and cholesteric liquid crystal microdroplets were modified specifically to achieve high sensitivity and selectivity. As a proof of concept, wavelength-multiplexed sensing and a prototype were demonstrated on human skin to detect human metabolites from perspiration. These results present a significant advance in the fabrication and potential guidance for wearable and functional microlasers in healthcare.

A prognostic model for triple-negative breast cancer patients with liver metastasis: A population-based study.

However, it is still difficult for clinicians to establish prognostic stratifications and therapeutic strategies because of the lack of tools for predicting the survival of triple-negative breast cancer patients with liver metastases (TNBC-LM). Based on clinical data from large populations, a sensitive and discriminative nomogram was developed and validated to predict the prognosis of TNBC patients with LM at initial diagnosis or at the later course. Introduction/background: Liver metastasis (LM) in TNBC patients is associated with significant morbidity and mortality. The objective of this study was to construct a clinical model to predict the survival of TNBC-LM patients. Materials and methods: Clinicopathologic data were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database and the Fifth Affiliated Hospital of Sun Yat-Sen University (FAFSYU). Based on patients with newly diagnosed TNBC with LM (nTNBC-LM) from the SEER database, a predictive nomogram was established and validated. Its predictive effect on TNBC patients with LM at later disease course by enrolling TNBC patients from FAFSYU who developed LM later. The prognostic effect of different treatment for nTNBC-LM was further assessed. Results: A prognostic model was developed and validated to predict the prognosis of TNBC-LM patients. For LM patients diagnosed at the initial or later treatment stage, the C-index (0.712, 0.803 and 0.699 in the training, validation and extended groups, respectively) and calibration plots showed the acceptable prognostic accuracy and clinical applicability of the nomogram. Surgical resection on the primary tumour and chemotherapy were found to be associated with significantly better overall survival (OS). Conclusion: A sensitive and discriminative model was developed to predict OS in TNBC-LM patients both at and after initial diagnosis.

Organic photoelectrochemical transistor aptasensor for dual-mode detection of DEHP with CRISPR-Cas13a assisted signal amplification.

Emerging organic photoelectrochemical transistors (OPECTs) with inherent amplification capabilities, good biocompatibility and even self-powered operation have emerged as a promising detection tool, however, they are still not widely studied for pollutant detection. In this paper, a novel OPECT dual-mode aptasensor was constructed for the ultrasensitive detection of di(2-ethylhexyl) phthalate (DEHP). MXene/In2S3/In2O3 Z-scheme heterojunction was used as a light fuel for ion modulation in sensitive gated OPECT biosensing. A transistor system based on poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) converted biological events associated with photosensitive gate achieving nearly a thousand-fold higher current gain at zero bias voltage. This work quantified the target DEHP by aptamer-specific induction of CRISPR-Cas13a trans-cutting activity with target-dependent rolling circle amplification as the signal amplification unit, and incorporated the signal changes strategy of biocatalytic precipitation and TMB color development. Combining OPECT with the auxiliary validation of colorimetry (CM), high sensitivity and accurate detection of DEHP were achieved with a linear range of 0.1 pM to 200 pM and a minimum detection limit of 0.02 pM. This study not only provides a new method for the detection of DEHP, but also offers a promising prospect for the gating and application of the unique OPECT.

Ir-Doped CuPd Single-Crystalline Mesoporous Nanotetrahedrons for Ethylene Glycol Oxidation Electrocatalysis: Enhanced Selective Cleavage of C-C Bond.

The development of highly efficient electrocatalysts for complete oxidation of ethylene glycol (EG) in direct EG fuel cells is of decisive importance to hold higher energy efficiency. Despite some achievements, their progress, especially electrocatalytic selectivity to complete oxidated C1 products, is remarkably slower than expected. In this work, we developed a facile aqueous synthesis of Ir-doped CuPd single-crystalline mesoporous nanotetrahedrons (Ir-CuPd SMTs) as high-performance electrocatalyst for promoting oxidation cleavage of C-C bond in alkaline EG oxidation reaction (EGOR) electrocatalysis. The synthesis relied on precise reduction/co-nucleation and epitaxial growth of Ir, Cu and Pd precursors with cetyltrimethylammonium chloride as the mesopore-forming surfactant and extra Br- as the facet-selective agent under ambient conditions. The products featured concave nanotetrahedron morphology enclosed by well-defined (111) facets, single-crystalline and mesoporous structure radiated from the center, and uniform elemental composition without any phase separation. Ir-CuPd SMTs disclosed remarkably enhanced electrocatalytic activity and excellent stability as well as superior selectivity of C1 products for alkaline EGOR electrocatalysis. Detailed mechanism studies demonstrated that performance improvement came from structural and compositional synergies, which kinetically accelerated transports of electrons/reactants within active sites of penetrated mesopores and facilitated oxidation cleavage of high-energy-barrier C-C bond of EG for desired C1 products. More interestingly, Ir-CuPd SMTs performed well in coupled electrocatalysis of anode EGOR and cathode nitrate reduction, highlighting its high potential as bifunctional electrocatalyst in various applications.

Rehabilitation care for pain in elderly knee replacement patients.

BACKGROUND: Total knee arthroplasty (TKA) is recognized as the most effective surgical intervention for relieving pain and improving joint mobility and deformity in patients with knee osteoarthritis and other synovial diseases. The application of accelerated postoperative rehabilitation (enhanced recovery after surgery) has demonstrated its efficacy in improving patient outcomes, and early postoperative joint function exercise has become a key prognostic factor in knee replacement. The unexpected appearance of limb pain and swelling hindered the patient's tendency for early mobilization, leading in prolonged hospitalization, delayed functional recovery and negative psychological responses. AIM: To investigate the impact of incorporating programmed pain nursing with collaborative nursing on elderly patients undergoing knee replacement surgery. METHODS: A retrospective analysis was conducted on a cohort of 116 patients who underwent TKA at our hospital between July 2019 and July 2021. The patients were divided into two groups: A control group (n = 58) receiving programmatic nursing, and an observed group (n = 58) receiving programmed nursing combined with a collaborative nursing model. A pain management team consisting of attending physicians, head nurses, and responsible nurses was established. Outcome measures included visual analogue scale (VAS) scores, activities of daily living (ADL) scale scores, and functional scores. RESULTS: The ADL scores of patients in both groups exhibited a continuous increase. However, there was no statistically significant difference in the ADL scores between the two groups at 48 h and the 7th d post-surgery (P > 0.05). Upon reexamination at the 3rd mo, the observation group demonstrated higher ADL scores compared to the control group (67.48 ± 14.69 vs 59.40 ± 16.06, P < 0.05). The VAS scores of both groups significantly decreased, with no significant difference observed between the groups at each time point (P > 0.05). The functional status of patients in both groups exhibited a gradual increase prior to intervention and at the 1st, 2nd, and 3rd month following discharge (P < 0.05). There was no statistically significant difference in knee joint function scores between the two groups at the 1st month after discharge (47.52 vs 45.81, P > 0.05). However, the knee joint function scores of patients in the observation group were significantly higher than those in the control group at the 2nd (59.38 vs 53.19, P < 0.05) and 3rd month (71.92 vs 64.34, P < 0.05) following discharge. CONCLUSION: The utilization of programmed pain nursing in conjunction with collaborative nursing for out-of-hospital care of TKA patients has demonstrated favorable outcomes, encompassing pain reduction, enhanced prognosis, and improved nursing quality for patients.

Based on Serum Pharmacochemistry and Virtual Screening Technique Analysis Used to Explore the Potential Active Ingredients and Possible Anti- Coronary Heart Disease Mechanisms of Salvia miltiorrhiza Bunge.

AIMS AND OBJECTIVE: This study aimed to identify the bioactive compounds and explore the multi-target mechanisms of Salvia miltiorrhiza Bunge (SMB) against coronary heart disease (CHD) using an integrated serum pharmacochemistry and network pharmacology approach. MATERIALS AND METHODS: The chemical constituents of SMB were characterized by UPLC-MS. The absorbed ingredients and metabolites after oral SMB administration were identified in rat serum. Therapeutic targets of SMB against CHD were predicted by intersecting the targets of absorbed compounds from databases and CHD-associated genes. Protein-protein interaction network, pathway analysis, molecular docking, and molecular dynamic simulation were performed. RESULTS: A total of 61 SMB-derived compounds were identified in rat serum. Network analysis revealed 111 candidate targets highly related to CHD pathways. Further topological analysis identified 10 hub targets and 20 key active compounds, constructing an informative compoundtarget- pathway network. PTGS2 and TNF were predicted as primary targets of SMB against CHD based on molecular dynamic simulation. CONCLUSION: This integrated approach identified bioactive compounds and multi-target mechanisms of SMB against CHD. The results provide scientific evidence supporting SMB's clinical efficacy and reveal potential anti-CHD targets.

Protein 4.1R regulates M1 macrophages polarization via glycolysis, alleviating sepsis-induced liver injury in mice.

Acute liver injury (ALI) is a common clinical disease caused by sepsis, metabolic syndrome, hepatitis virus. Macrophage plays an important role in the development of ALI, which is characterized by polarization and inflammatory regulation. The polarization process of macrophages is related to membrane binding proteins and adaptors. Protein 4.1R acts as an adaptor, linking membrane proteins to the cytoskeleton, and is involved in cell activation and cytokine secretion. However, whether protein 4.1R is involved in regulating macrophage polarization and inflammation-induced liver injury remains unknown. In this study, protein 4.1R is identified with the special effect on macrophage M1 polarization. And it is further demonstrated that protein 4.1R deficiency significantly enhance glycolytic metabolism. Mechanistically, the regulation of protein 4.1R on pyruvate kinase M2 (PKM2) plays a key role in glycolysis metabolism. In addition, we found that protein 4.1R directly interacts with toll-like receptor 4 (TLR4), inhibits the activation of the AKT/HIF-1α signaling pathway. In conclusion, protein 4.1R targets HIF-1α mediated glycolysis regulates M1 macrophage polarization, indicating that protein 4.1R is a candidate for regulating macrophage mediated inflammatory response. In conclusion, we have revealed a novel function of protein 4.1R in macrophage polarization and ALI, providing important insights into the metabolic reprogramming, which is important for ALI therapy. We have revealed a novel function of protein 4.1R in macrophage polarization and ALI, providing important insights into the metabolic reprogramming, which is important for ALI therapy.

CSMP: A Self-Assembled Plant Polysaccharide-Based Hydrofilm for Enhanced Wound Healing.

Wound management remains a critical healthcare issue due to the rising incidence of chronic diseases leading to persistent wounds. Traditional dressings have their limitations, such as potential for further damage during changing and suboptimal healing conditions. Recently, hydrogel-based dressings have gained attention due to their biocompatibility, biodegradability, and ability to fill wounds. Particularly, polysaccharide-based hydrogels have shown potential in various medical applications. This study focuses on the development of a novel hydrofilm wound dressing produced from a blend of chia seed mucilage (CSM) and polyvinyl alcohol (PVA), termed CSMP. While the individual properties of CSM and PVA are well-documented, their combined potential in wound management is largely unexplored. CSMP, coupled with sorbitol and glycerin, and cross-linked using ultraviolet light, results in a flexible, adhesive, and biocompatible hydrofilm demonstrating superior water absorption, moisturizing, and antibacterial properties. This hydrofilm promotes epithelial cell migration, enhanced collagen production, and outperforms existing commercial dressings in animal tests. The innovative CSMP hydrofilm offers a promising, cost-effective approach for improved wound care, bridging existing gaps in dressing performance and preparation simplicity. Future research can unlock further applications of such polysaccharide-based hydrofilm dressings.

Ultrathin Two-dimensional Layered Composite Carbosilicates from in situ Unzipped Carbon Nanotubes and Exfoliated Bulk Silica.

A key task in today's inorganic synthetic chemistry is to develop effective reactions, routes, and associated techniques aiming to create new functional materials with specifically desired multilevel structures and properties. Herein, we report an ultrathin two-dimensional layered composite of graphene ribbon and silicate via a simple and scalable one-pot reaction, which leads to the creation of a novel carbon-metal-silicate hybrid family: carbosilicate. The graphene ribbon is in situ formed by unzipping carbon nanotubes, while the ultrathin silicate is in situ obtained from bulk silica or commercial glass; transition metals (Fe or Ni) oxidized by water act as bridging agent, covalently bonding the two structures. The unprecedented structure combines the superior properties of the silicate and the nanocarbon, which triggers some specific novel properties. All processes during synthesis are complementary to each other. The associated synergistic chemistry could stimulate the discovery of a large class of more interesting, functionalized structures and materials.

Ephrin B3 exacerbates colitis and colitis-associated colorectal cancer.

Ephrin B3, a member of Eph/ephrin family, contributes to embryogenesis and carcinogenesis, but few studies have suggested whether this ligand has regulatory effect on colitis. This study was to determine whether ephrin B3 played a role in colitis and colonic carcinogenesis. Dextran sodium sulfate (DSS)-induced colitis and azoxymethane (AOM)/DSS-induced colitis-associated carcinogenesis model was established in Efnb3-deficient (Efnb3-/-) mice. Label-free quantitative proteomics were performed to identify the Efnb3-regulated proteins. Our results showed that Efnb3 knock out reduced the symptoms of DSS-induced colitis, such as disease activity index (DAI), inflammatory factors release, and dysfunction of the intestinal barrier. Quantitative proteomics revealed that Efnb3 regulated 95 proteins which clustered in the platelet degranulation, response to elevated platelet cytosolic Ca2+, MAPK signaling for integrins such as ITGB4. Furthermore, ephrin B3 inactived ITGB4/AKT signal pathway and then promoted epithelial barrier dysfunction. Simultaneously, ephrin B3 promoted Gremlin-1/NF-κB signal pathway and thereby increased inflammatory factors release. In addition, the higher level of Efnb3 in colon cancer patients is correlated with worse survival. Efnb3-/- mice exhibited susceptibility to AOM/DSS-induced colorectal cancer. Our finding discovered that Efnb3 played an important role in the development of colitis and colitis-associated colorectal cancer. Efnb3 deficiency improved the intestinal barrier by ITGB4 and suppressed inflammation via Gremlin-1/NF-κB signal pathway, which may provide a novel therapeutic strategy for the treatment of colitis and colitis-associated colorectal cancer.

Rapid Detection of Total Viable Count in Intact Beef Dishes Based on NIR Hyperspectral Hybrid Model.

The total viable count (TVC) of bacteria is an important index to evaluate the freshness and safety of dishes. To improve the accuracy and robustness of spectroscopic detection of total viable bacteria count in a complex system, a new method based on a near-infrared (NIR) hyperspectral hybrid model and Support Vector Machine (SVM) algorithms was developed to directly determine the total viable count in intact beef dish samples in this study. Diffuse reflectance data of intact and crushed samples were tested by NIR hyperspectral and processed using Multiplicative Scattering Correction (MSC) and Competitive Adaptive Reweighted Sampling (CARS). Kennard-Stone (KS) and Samples Set Partitioning Based on Joint X-Y Distance (SPXY) algorithms were used to select the optimal number of standard samples transferred by the model combined with root mean square error. The crushed samples were transferred into the complete samples prediction model through the Direct Standardization (DS) algorithm. The spectral hybrid model of crushed samples and full samples was established. The results showed that the Determination Coefficient of Calibration (RP2) value of the total samples prediction set increased from 0.5088 to 0.8068, and the value of the Root Mean Square Error of Prediction (RMSEP) decreased from 0.2454 to 0.1691 log10 CFU/g. After establishing the hybrid model, the RMSEP value decreased by 9.23% more than before, and the values of Relative Percent Deviation (RPD) and Reaction Error Relation (RER) increased by 12.12% and 10.09, respectively. The results of this study showed that TVC instewed beef samples can be non-destructively determined based on the DS model transfer method combined with the hybrid model strategy. This study provided a reference for solving the problem of poor accuracy and reliability of prediction models in heterogeneous samples.

[Characterization and phylogenetic analysis of complete chloroplast genome of cultivated Qinan agarwood].

"Tangjie" leaves of cultivated Qinan agarwood were used to obtain the complete chloroplast genome using high-throughput sequencing technology. Combined with 12 chloroplast genomes of Aquilaria species downloaded from NCBI, bioinformatics method was employed to determine the chloroplast genome characteristics and phylogenetic relationships. The results showed that the chloroplast genome sequence length of cultivated Qinan agarwood "Tangjie" leaves was 174 909 bp with a GC content of 36.7%. A total of 136 genes were annotated, including 90 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. Sequence repeat analysis detected 80 simple sequence repeats(SSRs) and 124 long sequence repeats, with most SSRs composed of A and T bases. Codon preference analysis revealed that AUU was the most frequently used codon, and codons with A and U endings were preferred. Comparative analysis of Aquilaria chloroplast genomes showed relative conservation of the IR region boundaries and identified five highly variable regions: trnD-trnY, trnT-trnL, trnF-ndhJ, petA-cemA, and rpl32, which could serve as potential DNA barcodes specific to the Aquilaria genus. Selection pressure analysis indicated positive selection in the rbcL, rps11, and rpl32 genes. Phylogenetic analysis revealed that cultivated Qinan agarwood "Tangjie" and Aquilaria agallocha clustered together(100% support), supporting the Chinese origin of Qinan agarwood from Aquilaria agallocha. The chloroplast genome data obtained in this study provide a foundation for studying the genetic diversity of cultivated Qinan agarwood and molecular identification of the Aquilaria genus.

Short- and long-term outcomes of Roux-en-Y and Billroth II with Braun reconstruction in total laparoscopic distal gastrectomy: a retrospective analysis.

BACKGROUND: The controversy surrounding Roux-en-Y (R-Y) and Billroth II with Braun (BII + B) reconstruction as an anti-bile reflux procedure after distal gastrectomy has persisted. Recent studies have demonstrated their efficacy, but the long-term outcomes and postoperative quality of life (QoL) among patients have yet to be evaluated. Therefore, we compared the short-term and long-term outcomes of the two procedures as well as QoL. METHODS: The clinical data of 151 patients who underwent total laparoscopic distal gastrectomy (TLDG) at the Gastrointestinal Surgery Department of the Second Hospital of Fujian Medical University from January 2016 to December 2019 were retrospectively analyzed. Of these, 57 cases with Roux-en-Y procedure (R-Y group) and 94 cases with Billroth II with Braun procedure were included (BII + B group). Operative and postoperative conditions, early and late complications, endoscopic outcomes at year 1 and year 3 after surgery, nutritional indicators, and quality of life scores at year 3 postoperatively were compared between the two groups. RESULTS: The R-Y group recorded a significantly longer operative time (194.65 ± 21.52 vs. 183.88 ± 18.02 min) and anastomotic time (36.96 ± 2.43 vs. 27.97 ± 3.74 min) compared to the BII + B group (p < 0.05). However, no other significant differences were observed in terms of perioperative variables, including blood loss (p > 0.05). Both groups showed comparable rates of early and late complications. Endoscopic findings indicated similar food residuals at years 1 and 3 post-surgery for both groups. The R-Y group had a lower occurrence of residual gastritis and bile reflux at year 1 and year 3 after surgery, with a statistically significant difference (p < 0.001). Reflux esophagitis was not significantly different between the R-Y and BII + B groups in year 1 after surgery (p = 0.820), but the R-Y group had a lower incidence than the BII + B group in year 3 after surgery (p = 0.023). Nutritional outcomes at 3 years after surgery did not differ significantly between the two groups (p > 0.05). Quality of life scores measured by the QLQ-C30 scale were not significantly different between the two groups. However, on the QLQ-STO22 scale, the reflux score was significantly lower in the R-Y group than in the BII + B group (0 [0, 0] vs. 5.56 [0, 11.11]) (p = 0.003). The rest of the scores were not significantly different (p > 0.05). CONCLUSION: Both R-Y and B II + B reconstructions are equally safe and efficient for TLDG. Nevertheless, the R-Y reconstruction reduces the incidence of residual gastritis, bile reflux, and reflux esophagitis, as well as postoperative reflux symptoms, and provides a better quality of life for patients. R-Y reconstruction is superior to BII + B reconstruction for TLDG.

Association between leptin receptor polymorphisms and polycystic ovary syndrome risk: a meta-analysis based on 11 studies.

OBJECTIVE: Published evidence indicated that the leptin receptor (LEPR) gene polymorphisms are associated with polycystic ovary syndrome (PCOS) risk. However, studies on the association between the polymorphisms of LEPR gene are inconsistent or even controversial. MATERIAL AND METHODS: We conducted this meta-analysis to explore the more precise relationship between LEPR polymorphisms and PCOS risk. Relevant articles were searched with five online databases up to March 1 2023. Odds ratios (OR) with 95% confidence intervals (CI) were selected to examine the statistical strength of each genetic model. Moreover, RNA secondary structure and variant effects of these loci were examined with in silico analysis. RESULTS: Overall, 11 publications were analyzed, and the pooled results did not present any significant association between rs1137101 A/G polymorphism and PCOS risk in general population and some subgroup analysis. But the significant association were observed in Asian population (AG vs. AA: OR = 0.51, 95%CI = 0.32-0.81, p = .01, I2=0%; AG + GG vs. AA: OR = 0.41, 95%CI = 0.26-0.65, p < .01, I2=25.9%). Moreover, similar positive associations were also observed in rs1805096 polymorphism with PCOS risk. CONCLUSION: In summary, our meta-analysis suggested that the LEPR gene polymorphisms might be associated with PCOS susceptibility. Owing to the limited studies and small sample size in our meta-analysis, more well-designed studies from different races were needed to be conducted to verify the current results.

Comparison of short-term and long-term clinical effects of modified overlap anastomosis and conventional incision-assisted anastomosis in laparoscopic total gastrectomy.

BACKGROUND: To compare short-term and long-term clinical effects of modified overlap anastomosis and conventional incision-assisted anastomosis for laparoscopic total gastrectomy. METHODS: This retrospective cohort study included patients with gastric cancer admitted to the Second Affiliated Hospital of Fujian Medical University from January 2016 to March 2020. Quality of life, intraoperative and postoperative conditions were analyzed. RESULTS: Compared with the conventional assisted group, the modified overlap group showed a shorter auxiliary incision, milder postoperative pain, shorter time to the first postoperative anal exhaust, shorter time to the first postoperative liquid food intake, and shorter postoperative stay. There were no differences between the two groups regarding operation time, esophagus-jejunum anastomosis time, intraoperative blood loss, number of lymph nodes dissected, and length of the upper incision margin. There were no differences between the two groups regarding postoperative early and late complications. There were no differences between the two groups regarding the QLQ-C30 scale three years after the operation. The scores of the QLQ-STO22 scale 3 years after the operation showed significantly lower scores for dysphagia and feeding limit in the modified overlap group than those in the conventional assisted anastomosis group. There was no recurrence in the modified overlap group but one patient in the conventional assisted group. CONCLUSIONS: Patients undergoing totally laparoscopic total gastrectomy with modified overlap anastomosis have better minimal invasiveness and faster post-operative recovery than conventional incision-assisted anastomosis.

Comparison of proximal gastrectomy with double-flap technique and double-tract reconstruction for proximal early gastric cancer: a meta-analysis.

Surgical resection is the main treatment for proximal gastric cancer, but there is no consensus on its reconstruction. We carried out a meta-analysis to evaluate the effects of double-tract reconstruction (DTR) and double-flap technique (DFT) on postoperative quality of life in patients with proximal gastric cancer. Systematic searches of PubMed, Web of Science, EBSCO, and the Cochrane Library were performed. Literature for the last 5 years was searched without language restrictions. The cutoff date for the search was 12 April 2023. Literature and research searches were conducted independently by two researchers and data were extracted. Statistical analyses were performed using Review Manager (Revman) 5.4 software. Fixed models were used when heterogeneity was small and random-effects models were used for meta-analysis when heterogeneity was large. The study was registered with PROSPERO, CRD 42023418520. Surgical time was significantly shorter in the DTR group than in the DFT group (P = 0.03). There were no significant differences between DFT and DTR in terms of age, gender, pathological stage, preoperative body mass index, surgical bleeding, and perioperative complications. There was no statistically significant difference between the two groups in terms of reflux esophagitis and PPI intake, but DFT was superior to DTR in weight improvement at 1 year after surgery (P < 0.0001). Compared with DTR, DFT reconstruction is more demanding and time-consuming, but its postoperative nutritional status is better, so it should be the first choice for GI reconstruction in most patients with early proximal gastric cancer. However, DTR should be the best choice for patients who have difficulty operating.

A Bischler-Napieralski and homo-Mannich sequence enables diversified syntheses of sarpagine alkaloids and analogues.

Sarpagine alkaloids offer signicant opportunities in drug discovery, yet the efficient total syntheses and diverse structural modifications of these natural products remain highly challenging due to the architectural complexity. Here we show a homo-Mannich reaction of cyclopropanol with imines generated via a Bischler-Napieralski reaction enables a protecting-group-free, redox economic, four-step access to the tetracyclic sarpagine core from L-tryptophan esters. Based on this advancement, diversified syntheses of sarpagine alkaloids and analogues are achieved in a short synthetic route. The systematic anticancer evaluation indicates that natural products vellosimine and Na-methyl vellosimine possess modest anticancer activity. Intensive structural optimization of these lead molecules and exploration of the structure-activity relationship lead to the identification of analogue 15ai with an allene unit showing a tenfold improvement in anticancer activities. Further mechanism studies indicate compound 15ai exertes antiproliferation effects by inducing ferroptosis, which is an appealing non-apoptotic cell death form that may provide new solutions in future cancer therapies.

Periodic Mesoporous Organosilica as a Nanoadjuvant for Subunit Vaccines Elicits Potent Antigen-Specific Germinal Center Responses by Activating Naive B Cells.

Infection diseases such as AIDS and COVID-19 remain challenging in regard to protective vaccine design, while adjuvants are critical for subunit vaccines to induce strong, broad, and durable immune responses against variable pathogens. Here, we demonstrate that periodic mesoporous organosilica (PMO) acts as a multifunctional nanoadjuvant by adsorbing recombinant protein antigens. It can effectively deliver antigens to lymph nodes (LNs), prolong antigen exposure, and rapidly elicit germinal center (GC) responses by directly activating naive B cells via the C-type lectin receptor signaling pathway. In mice, both the gp120 trimer (HIV-1 antigen) and the receptor-binding domain (SARS-CoV-2 antigen) with the PMO nanoadjuvant elicit potent and durable antibodies that neutralize heterologous virus strains. LN immune cells analysis shows that PMO helps to effectively activate the T-follicular helper cells, GC B cells, and memory B cells and eventually develop broad and durable humoral responses. Moreover, the PMO nanoadjuvant elicits a strong cellular immune response and shapes this immune response by eliciting high levels of effector T helper cell cytokines. This study identifies a promising nanoadjuvant for subunit vaccines against multiple pathogens.

Enhancement of Microglia Functions by Developed Nano-Immuno-Synergist to Ameliorate Immunodeficiency for Malignant Glioma Treatment.

Resident microglia are key factors in mediating immunity against brain tumors, but the microglia in malignant glioma are functionally impaired. Little immunotherapy is explored to restore microglial function against glioma. Herein, oleanolic acid (OA) (microglia "restorer") and D PPA-1 peptide (immune checkpoint blockade) are integrated on a nano-immuno-synergist (D PAM@OA) to work coordinately. The self-assembled OA core is coated with macrophage membrane for efficient blood-brain barrier penetration and microglia targeting, on which D PPA-1 peptide is attached via acid-sensitive bonds for specific release in tumor microenvironment. With the enhanced accumulation of the dual drugs in their respective action sites, D PAM@OA effectively promotes the recruitment and activation of effector T cells by inhibiting aberrant activation of Signal transducer and activator of transcription (STAT-3) pathway in microglia, and assists activated effector T cells in killing tumor cells by blocking elevated immune checkpoint proteins in malignant glioma. Eventually, as adjuvant therapy, the rationally designed nano-immuno-synergist hinders malignant glioma progression and recurrence with or without temozolomide. The work demonstrates the feasibility of a nano-formulation for microglia-based immunotherapy, which may provide a new direction for the treatment of brain tumors.