A pan-tissue DNA methylation atlas enables in silico decomposition of human tissue methylomes at cell-type resolution.

Bulk-tissue DNA methylomes represent an average over many different cell types, hampering our understanding of cell-type-specific contributions to disease development. As single-cell methylomics is not scalable to large cohorts of individuals, cost-effective computational solutions are needed, yet current methods are limited to tissues such as blood. Here we leverage the high-resolution nature of tissue-specific single-cell RNA-sequencing datasets to construct a DNA methylation atlas defined for 13 solid tissue types and 40 cell types. We comprehensively validate this atlas in independent bulk and single-nucleus DNA methylation datasets. We demonstrate that it correctly predicts the cell of origin of diverse cancer types and discovers new prognostic associations in olfactory neuroblastoma and stage 2 melanoma. In brain, the atlas predicts a neuronal origin for schizophrenia, with neuron-specific differential DNA methylation enriched for corresponding genome-wide association study risk loci. In summary, the DNA methylation atlas enables the decomposition of 13 different human tissue types at a high cellular resolution, paving the way for an improved interpretation of epigenetic data.

STK33 Phosphorylates Fibrous Sheath Protein AKAP3/4 to Regulate Sperm Flagella Assembly in Spermiogenesis.

Spermatogenesis defects are important for male infertility; however, the etiology and pathogenesis are still unknown. Herein, we identified two loss-of-function mutations of STK33 in seven individuals with non-obstructive azoospermia. Further functional studies of these frameshift and nonsense mutations revealed that Stk33-/KI male mice were sterile, and Stk33-/KI sperm were abnormal with defects in the mitochondrial sheath, fibrous sheath, outer dense fiber, and axoneme. Stk33KI/KI male mice were subfertile and had oligoasthenozoospermia. Differential phosphoproteomic analysis and in vitro kinase assay identified novel phosphorylation substrates of STK33, fibrous sheath components A-kinase anchoring protein 3 and A-kinase anchoring protein 4, whose expression levels decreased in testis after deletion of Stk33. STK33 regulated the phosphorylation of A-kinase anchoring protein 3/4, affected the assembly of fibrous sheath in the sperm, and played an essential role in spermiogenesis and male infertility.

ARID1A loss promotes RNA editing of CDK13 in an ADAR1-dependent manner.

BACKGROUND: ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, is thought to play a significant role both in tumor suppression and tumor initiation, which is highly dependent upon context. Previous studies have suggested that ARID1A deficiency may contribute to cancer development. The specific mechanisms of whether ARID1A loss affects tumorigenesis by RNA editing remain unclear. RESULTS: Our findings indicate that the deficiency of ARID1A leads to an increase in RNA editing levels and alterations in RNA editing categories mediated by adenosine deaminases acting on RNA 1 (ADAR1). ADAR1 edits the CDK13 gene at two previously unidentified sites, namely Q113R and K117R. Given the crucial role of CDK13 as a cyclin-dependent kinase, we further observed that ADAR1 deficiency results in changes in the cell cycle. Importantly, the sensitivity of ARID1A-deficient tumor cells to SR-4835, a CDK12/CDK13 inhibitor, suggests a promising therapeutic approach for individuals with ARID1A-mutant tumors. Knockdown of ADAR1 restored the sensitivity of ARID1A deficient cells to SR-4835 treatment. CONCLUSIONS: ARID1A deficiency promotes RNA editing of CDK13 by regulating ADAR1.

Molecular Engineering of Pure Superoxide Radical Photogenerator for Hypoxia-Tolerant Tumor Theranostics.

Photodynamic therapy (PDT) is a promising cancer treatment, but limited oxygen supply in tumors (hypoxia) can hinder its effectiveness. This is because traditional PDT relies on Type-II reactions that require oxygen. Type-I photosensitizers (PSs) offer a promising approach to overcome the limitations of tumor photodynamic therapy (PDT) in hypoxic environments. To leverage the advantages of Type-I PDT, the design and evaluation of a series of Type-I PSs for developing pure Type-1 PSs, by incorporating benzene, thiophene, or bithiophene into the donor-acceptor molecular skeleton are reported. Among them, CTTI (with bithiophene) shows the best performance, generating the most superoxide radical (O2 •-) upon light irradiation. Importantly, CTTI exclusively produced superoxide radicals, avoiding the less effective Type-II pathway. This efficiency is due to CTTI's energy gap and low reduction potential, which favor electron transfer to oxygen for O2 •- generation. Finally, CTTI NPs are successfully fabricated by encapsulating CTTI into liposomes, and validated to be effective in killing tumor cells, even under hypoxic conditions, making them promising hypoxia-tolerant tumor phototheranostic agents in both in vitro and in vivo applications.

Surface-Engineered Polygonatum Sibiricum Polysaccharide CaCO3 Microparticles as Novel Vaccine Adjuvants to Enhance Immune Response.

Micro- and nanoparticles delivery systems have been widely studied as vaccine adjuvants to enhance immunogenicity and sustain long-term immune responses. Polygonatum sibiricum polysaccharide (PSP) has been widely studied as an immunoregulator in improving immune responses. In this study, we synthesized and characterized cationic modified calcium carbonate (CaCO3) microparticles loaded with PSP (PEI-PSP-CaCO3, CTAB-PSP-CaCO3), studied the immune responses elicited by PEI-PSP-CaCO3 and CTAB-PSP-CaCO3 carrying ovalbumin (OVA). Our results demonstrated that PEI-PSP-CaCO3 significantly enhanced the secretion of IgG and cytokines (IL-4, IL-6, IFN-γ, and TNF-α) in vaccinated mice. Additionally, PEI-PSP-CaCO3 induced the activation of dendritic cells (DCs), T cells, and germinal center (GC) B cells in draining lymph nodes (dLNs). It also enhanced lymphocyte proliferation, increased the ratio of CD4+/CD8+ T cells, and elevated the frequency of CD3+ CD69+ T cells in spleen lymphocytes. Therefore, PEI-PSP-CaCO3 microparticles induced a stronger cellular and humoral immune response and could be potentially useful as a vaccine delivery and adjuvant system.

Intravenous methylprednisolone for nephrotic syndrome with minimal change lesions in adults: a randomized controlled trial.

BACKGROUND AND HYPOTHESIS: Patients with minimal change nephrotic syndrome (MCNS) usually experienced severe edema which can affect the absorption of oral corticosteroid during the first 2 weeks. We conducted a randomized controlled trial to compare the efficacy of intravenous isovalent methylprednisolone induction followed by oral prednisone therapy with conventional oral prednisone therapy in highly edematous MCNS patients, aiming to provide a better therapy for MCNS patients. METHODS: A single-center, open-label, parallel-arm randomized controlled trial was performed in the Nephrology Department of the Affiliated Hospital of Guangdong Medical University. Patients who met the inclusion were enrolled in our study from May 2015 to October 2020, and were randomized to receive conventional oral steroid or 2 weeks intravenous methylprednisolone followed by oral prednisone. RESULTS: 117 patients were enrolled and randomly assigned to either the sequential group (N = 57) or the oral group (N = 60). Total remission rate in the sequential group was higher than the oral group after treatment for 2 weeks and 4 weeks (P = 0.032, P = 0.027). Complete remission rate was higher in the sequential group than in the oral group (63.3% vs. 41.5%, P = 0.031) after treatment for 2 weeks. The time to achieve CR is shorter in the sequential group than the oral group, with a statistically significant difference (14.0 days, 95% CI [13.5 to 14.5] vs. 16.0 days, 95% CI [12.7 to 19.3], P = 0.024). There were no significant difference in relapse rate (24.5% vs 28.3%, P = 0.823) and time to relapse (155 ± 103 days vs 150.7 ± 103.7 days, P = 0.916) between two groups. CONCLUSION: This study suggested that highly edematous MCNS patients received intravenously isovalent methylprednisolone induction therapy follow by oral prednisone achieved earlier remission than the conventional oral prednisone regimen without differences in relapse rates or adverse effects. Short-term intravenous methylprednisolone followed by oral prednisone may be a better choice for MCNS patients with highly edema.

Restoring translational symmetry in periodic all-orbital dynamical mean-field theory simulations.

Dynamical mean-field theory (DMFT) and its cluster extensions provide an efficient Green's function formalism to simulate spectral properties of periodic systems at the quantum many-body level. However, traditional cluster DMFT breaks translational invariance in solid-state materials, and the best strategy to capture non-local correlation effects within cluster DMFT remains elusive. In this work, we investigate the use of overlapping atom-centered impurity fragments in recently-developed ab initio all-orbital DMFT, where all local orbitals within the impurity are treated with high-level quantum chemistry impurity solvers. We demonstrate how the translational symmetry of the lattice self-energy can be restored by designing symmetry-adapted embedding problems, which results in an improved description of spectral functions in two-dimensional boron nitride monolayers and graphene at the levels of many-body perturbation theory (GW) and coupled-cluster theory. Furthermore, we study the convergence of self-energy and density of states as the embedding size is systematically expanded in one-shot and self-consistent DMFT calculations.

Cholinium Pyridinolate Ionic Pair-Catalyzed Fixation of CO2 into Cyclic Carbonates.

A halide-free ionic pair organocatalyst was proposed for the cycloaddition of CO2 into epoxide reactions. Cholinium pyridinolate ionic pairs with three different substitution positions were designed. Under conditions of temperature of 120 °C, pressure of 1 MPa CO2, and catalyst loading of 5 mol %, the optimal catalyst cholinium 4-pyridinolate ([Ch]+[4-OP]-) was employed. After a reaction time of 12 h, styrene oxide was successfully converted into the corresponding cyclic carbonate, and its selectivity was improved to 90%. A series of terminal epoxides were converted into cyclic carbonates within 12 h, with yields ranging from 80 to 99%. The proposed mechanism was verified by 1H NMR and 13C NMR titrations. Cholinium cations act as a hydrogen bond donor to activate epoxides, and pyridinolate anions combine with carbon dioxide to form intermediate carbonate anions that attack epoxides as nucleophiles and lead to ring opening. In summary, a halide-free ionic pair organocatalyst was designed and the catalytic mechanism in the cycloaddition of CO2 into epoxides reactions was proposed.

Improvements and challenges in intraperitoneal laparoscopic para-aortic lymphadenectomy: The novel "tent-pitching" antegrade approach and vascular anatomical variations in the para-aortic region.

INTRODUCTION: This study introduces and compares a new intraperitoneal laparoscopic para-aortic lymphadenectomy method to reach the level of the renal vein, the "tent-pitching" antegrade approach with the retrograde approach in gynecological malignancy surgeries in terms of success rate, complication incidence, and the number of lymph nodes removed. It focuses on the feasibility, safety, and effectiveness. Meanwhile, this article reports on the vascular anatomical variations discovered in the para-aortic region to enhance surgical safety. MATERIAL AND METHODS: This was a retrospective cohort study including patients undergone laparoscopic para-aortic lymphadenectomy at a single center from January 2020 to December 2023 for high-risk endometrial and early-stage ovarian cancer. Patient charts were reviewed for mode of operation, perioperative complications, operative details, and histopathology. The patients were divided into anterograde group and retrograde group according to the operation mode. The two groups were further compared based on the success rate of lymph node clearance at the renal vein level, perioperative complications, and the number of removed lymph nodes. Quantitative data were analyzed using the t-test, non-normally distributed data using the rank-sum test, and categorical data using Fisher's exact test and the chi-square test, with statistical significance defined as P < 0.05. RESULTS: Among 173 patients, the antegrade group showed higher surgery success (97.5% vs 68.82%), more lymph nodes removed (median 14 vs 7), and less median blood loss. The operation time was shorter in the antegrade group. Postoperative complications like lymphocele and venous thrombosis were lower in the antegrade group. Vascular abnormalities were found in 28.9% of patients, with accessory lumbar vein routing anomaly and accessory renal arteries being most common. CONCLUSIONS: The antegrade approach is feasible, safe, and effective, improving surgical exposure, reducing difficulty without additional instruments or puncture sites, and minimizing organ damage risk. It is effective in achieving better access to the renal vein and removing more para-aortic lymph nodes than the retrograde method. Recognizing and carefully managing the diverse vascular abnormalities in the para-aortic area, including variations in renal arteries, veins, and the inferior vena cava, is essential to reduce intraoperative bleeding and the likelihood of converting to open surgery.

Rosa laevigata Polysaccharides Ameliorate Dextran Sulfate Sodium-Induced Ulcerative Colitis of Beagles through Regulating Gut Microbiota.

Rosa laevigata Michx. polysaccharides (RLP) have been demonstrated to possess antioxidant and anti-inflammatory properties. However, the mechanisms and efficacy of these polysaccharide components in preventing ulcerative colitis (UC) remain to be elucidated. The efficacy and mechanisms of RLP were investigated in a study that utilized healthy adult beagles to establish a UC model, considering the similarities in gut microbiota between humans and dogs. In the study, the beagle model induced by sodium dextran sulfate exhibited typical symptoms of ulcerative colitis, such as weight loss and diarrhea. All these symptoms and changes were significantly ameliorated through oral supplementation of RLP. Additionally, microbial community analysis based on the 16S rDNA gene revealed that RLP alleviated UC by increasing the abundance of beneficial bacteria and reducing the abundance of harmful bacteria. In conclusion, our study has provided that RLP effectively alleviated colitis by preserving the intestinal barrier and regulating the gut microbiota composition.

Structural Characterization and In Vitro Anti-Inflammatory Activity of Polysaccharides Isolated from the Fruits of Rosa laevigata.

RLPa-2 (Mw 15.6 kDa) is a polysaccharide isolated from Rosa laevigata Michx. It consists of arabinose (Ara), galactose (Gal), rhamnose (Rha), glucose (Glc), xylose (Xyl), and galacturonic acid (Gal-UA) with a molar ratio of 1.00:0.91:0.39:0.34:0.25:0.20. Structural characterization was performed by methylation and NMR analysis, which indicated that RLPa-2 might comprise →6)-α-D-Galp-(1→, →4)-α-D-GalpA-(1→, α-L-Araf-(1→, →2,4)-α-D-Glcp-(1→, ß-D-Xylp, and α-L-Rhap. In addition, the bioactivity of RLPa-2 was assessed through an in vitro macrophage polarization assay. Compared to positive controls, there was a significant decrease in the expression of M1 macrophage markers (CD80, CD86) and p-STAT3/STAT3 protein. Additionally, there was a down-regulation in the production of pro-inflammatory mediators (NO, IL-6, TNF-α), indicating that M1 macrophage polarization induced with lipopolysaccharide (LPS) and interferon-γ (IFN-γ) stimulation could be inhibited by RLPa-2. These findings demonstrate that the RLPa-2 might be considered as a potential anti-inflammatory drug to reduce inflammation.

Rh-Catalyzed [4 + 1] Reaction of Cyclopropyl-Capped Dienes (but not Common Dienes) and Carbon Monoxide: Reaction Development and Mechanistic Study.

Transition-metal-catalyzed [4 + 1] reaction of dienes and carbon monoxide (CO) is the most straightforward and easily envisioned cyclization for the synthesis of five-membered carbocycles, which are ubiquitously found in natural products and functional molecules. Unfortunately, no test of this reaction was reported, and consequently, chemists do not know whether such kind of reaction works or not. Herein, we report that the [4 + 1] reaction of common dienes and CO cannot work, at least under the catalysis of [Rh(cod)Cl]2. However, using cyclopropyl-capped dienes (also named allylidenecyclopropanes) as substrates, the corresponding [4 + 1] reaction with CO proceeds smoothly in the presence of [Rh(cod)Cl]2. This [4 + 1] reaction, with a broad scope, provides efficient access to five-membered carbocyclic compounds of spiro[2.4]hept-6-en-4-ones. The [4 + 1] cycloadducts can be further transformed into other molecules by using the unique chemistry of cyclopropyl groups present in these molecules. The mechanism of this [4 + 1] reaction has been investigated by quantum chemical calculations, uncovering that cyclopropyl-capped dienes are strained dienes and the oxidative cyclization step in the [4 + 1] catalytic cycle can release this (angular) strain both kinetically and thermodynamically. The strain release in this step then propagates to all followed CO coordination/CO insertion/reductive elimination steps in the [4 + 1] catalytic cycle, helping the realization of this cycloaddition reaction. In contrast, common dienes (including cyclobutyl-capped dienes) do not have such advantages and their [4 + 1] reaction suffers from energy penalty in all steps involved in the [4 + 1] catalytic cycle. The reactivity of ene-allenes for the [4 + 1] reaction with CO is also discussed.

MYC-targeted genes predict distant recurrence in patients with ocular adnexal extranodal marginal zone lymphoma.

Ocular adnexal extranodal marginal zone lymphoma (OA-EMZL) is the most frequent subtype of ocular adnexal lymphoma, with a high propensity for recurrence. Distant recurrence (DR) as an essential prognostic event has unique clinical risk factors, but whether distinct molecular features exist remains poorly understood. Here, we identified potential biomarkers using proteomic analysis of 27 OA-EMZL samples. The MYC-targeted genes PCNA, MCM6, and MCM4 were identified as candidates. MYC-targeted genes were further identified as the most significantly activated gene set in patients with DR. The candidate genes were verified in samples from 11 patients with DR and 33 matched controls using immunohistochemistry. The 3-year and 5-year AUC values of MCM6 (0.699 and 0.757) were higher than those of Ki-67 (0.532 and 0.592). High expressions of MCM6 and MCM4 were significantly associated with shorter distant recurrence-free survival (Log-rank p = 0.017, Log-rank p = 0.0053). Multivariate Cox regression identified MCM6 expression as an independent risk factor for DR (HR, 6.86; 95% CI, 1.32-35.79; P = 0.02). Knockdown of c-Myc in B cells resulted in decreased MCM6 and MCM4 expression and reduced proliferative capacity. Our results suggest that activation of the MYC-targeted gene is a distinct molecular feature of DR in OA-EMZL. MYC-targeted gene, MCM6, is a promising pathological biomarker for DR.

The Dawn of a New Era: Tumor-Targeting Boron Agents for Neutron Capture Therapy.

Cancer is widely recognized as one of the most devastating diseases, necessitating the development of intelligent diagnostic techniques, targeted treatments, and early prognosis evaluation to ensure effective and personalized therapy. Conventional treatments, unfortunately, suffer from limitations and an increased risk of severe complications. In light of these challenges, boron neutron capture therapy (BNCT) has emerged as a promising approach for cancer treatment with unprecedented precision to selectively eliminate tumor cells. The distinctive and promising characteristics of BNCT hold the potential to revolutionize the field of oncology. However, the clinical application and advancement of BNCT technology face significant hindrance due to the inherent flaws and limited availability of current clinical drugs, which pose substantial obstacles to the practical implementation and continued progress of BNCT. Consequently, there is an urgent need to develop efficient boron agents with higher boron content and specific tumor-targeting properties. Researchers aim to address this need by integrating tumor-targeting strategies with BNCT, with the ultimate goal of establishing BNCT as an effective, readily available, and cutting-edge treatment modality for cancer. This review delves into the recent advancements in integrating tumor-targeting strategies with BNCT, focusing on the progress made in developing boron agents specifically designed for BNCT. By exploring the current state of BNCT and emphasizing the prospects of tumor-targeting boron agents, this review provides a comprehensive overview of the advancements in BNCT and highlights its potential as a transformative treatment option for cancer.

Cationic Nanoparticle-Stabilized Vaccine Delivery System for the H9N2 Vaccine to Promote Immune Response in Chickens.

Chinese yam polysaccharides (CYPs) have received wide attention for their immunomodulatory activity. Our previous studies had discovered that the Chinese yam polysaccharide PLGA-stabilized Pickering emulsion (CYP-PPAS) can serve as an efficient adjuvant to trigger powerful humoral and cellular immunity. Recently, positively charged nano-adjuvants are easily taken up by antigen-presenting cells, potentially resulting in lysosomal escape, the promotion of antigen cross-presentation, and the induction of CD8 T-cell response. However, reports on the practical application of cationic Pickering emulsions as adjuvants are very limited. Considering the economic damage and public-health risks caused by the H9N2 influenza virus, it is urgent to develop an effective adjuvant for boosting humoral and cellular immunity against influenza virus infection. Here, we applied polyethyleneimine-modified Chinese yam polysaccharide PLGA nanoparticles as particle stabilizers and squalene as the oil core to fabricate a positively charged nanoparticle-stabilized Pickering emulsion adjuvant system (PEI-CYP-PPAS). The cationic Pickering emulsion of PEI-CYP-PPAS was utilized as an adjuvant for the H9N2 Avian influenza vaccine, and the adjuvant activity was compared with the Pickering emulsion of CYP-PPAS and the commercial adjuvant (aluminum adjuvant). The PEI-CYP-PPAS, with a size of about 1164.66 nm and a ζ potential of 33.23 mV, could increase the H9N2 antigen loading efficiency by 83.99%. After vaccination with Pickering emulsions based on H9N2 vaccines, PEI-CYP-PPAS generated higher HI titers and stronger IgG antibodies than CYP-PPAS and Alum and increased the immune organ index of the spleen and bursa of Fabricius without immune organ injury. Moreover, treatment with PEI-CYP-PPAS/H9N2 induced CD4+ and CD8+ T-cell activation, a high lymphocyte proliferation index, and increased cytokine expression of IL-4, IL-6, and IFN-γ. Thus, compared with the CYP-PPAS and aluminum adjuvant, the cationic nanoparticle-stabilized vaccine delivery system of PEI-CYP-PPAS was an effective adjuvant for H9N2 vaccination to elicit powerful humoral and cellular immune responses.

microRNA-301b-3p from mesenchymal stem cells-derived extracellular vesicles inhibits TXNIP to promote multidrug resistance of gastric cancer cells.

OBJECTIVE: MicroRNAs (miRNAs) from mesenchymal stem cells (MSC)-derived extracellular vesicles (MSCs-EVs), including exosomes, are known to participate in different diseases. However, the function of miR-301b-3p from MSCs-EVs on the chemoresistance of gastric cancer (GC) cells remains poorly characterized. Thus, we aim to explore the role of MSCs-EVs-derived miR-301b-3p in multidrug resistance of GC cells. METHODS: Cisplatin (DDP)/vincristine (VCR)-resistant and sensitive GC clinical samples were harvested to detect expression of miR-301b-3p and thioredoxin interacting protein (TXNIP). MSCs were respectively transfected with miR-301b-3p oligonucleotides and/or TXNIP plasmids to extract the EVs, which were then co-cultured with multidrug-resistant GC cells. Then, P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP), IC50, proliferation, migration, and apoptosis of resistant GC cells were determined. The tumor growth was observed in nude mice. Targeting relationship between miR-301b-3p and TXNIP was confirmed. RESULTS: miR-301b-3p was upregulated, and TXNIP was downregulated in DDP/VCR-resistant GC tissues and cells. MSC-EVs induced drug resistance, proliferation, and migration and inhibited apoptosis of DDP/VCR-resistant GC cells in vitro, as well as facilitated tumor growth in vivo. Inhibition of miR-301b-3p or upregulation of TXNIP reversed the promoting effect of MSC-EVs on DDP/VCR resistant GC cells to DDP/VCR resistance and malignant behaviors. The effects of MSC-EVs carrying miR-301b-3p inhibition on DDP/VCR-resistant GC cells were reversed by TXNIP downregulation. TXNIP was confirmed as a target gene of miR-301b-3p. CONCLUSION: miR-301b-3p from MSCs-EVs inhibits TXNIP to promote multidrug resistance of GC cells, providing a novel insight for chemotherapy in GC.

Comprehensive transcriptomic profiling and mutational landscape of primary gastric linitis plastica.

BACKGROUND: Primary gastric linitis plastica (GLP) is a distinct phenotype of gastric cancer with poor survival. Comprehensive molecular profiles and putative therapeutic targets of GLP remain undetermined. METHODS: We subjected 10 tumor-normal tissue pairs to whole exome sequencing (WES) and whole transcriptome sequencing (WTS). 10 tumor samples were all GLP which involves 100% of the gastric wall macroscopically. TCGA data were compared to generate the top mutated genes and the overexpressed genes in GLP. RESULTS: Our results reveal that GLP has distinctive genomic and transcriptomic features, dysfunction in the Hippo pathway is likely to be a key step during GLP development. 6 genes were identified as significantly highly mutated genes in GLP, including AOX1, ANKRD36C, CPXM1, PTPN14, RPAP1, and DCDC1). MUC6, as a previously identified gastric cancer driver gene, has a high mutation rate (20%) in GLP. 20% of patients in our GLP cohort had CDH1 mutations, while none had RHOA mutations. GLP exhibits high immunodeficiency and low AMPK pathway activity. Our WTS results showed that 3 PI3K-AKT pathway-related genes (PIK3R2, AKT3, and IGF1) were significantly up-regulated in GLP. Two genes were identified using immunohistochemistry (IHC), IGF2BP3 and MUC16, which specifically expressed in diffuse-type-related gastric cancer cell lines, and its knockdown inhibits PI3K-AKT pathway activity. CONCLUSIONS: We provide the first integrative genomic and transcriptomic profiles of GLP, which may facilitate its diagnosis, prognosis, and treatment.

Block2: A comprehensive open source framework to develop and apply state-of-the-art DMRG algorithms in electronic structure and beyond.

block2 is an open source framework to implement and perform density matrix renormalization group and matrix product state algorithms. Out-of-the-box it supports the eigenstate, time-dependent, response, and finite-temperature algorithms. In addition, it carries special optimizations for ab initio electronic structure Hamiltonians and implements many quantum chemistry extensions to the density matrix renormalization group, such as dynamical correlation theories. The code is designed with an emphasis on flexibility, extensibility, and efficiency and to support integration with external numerical packages. Here, we explain the design principles and currently supported features and present numerical examples in a range of applications.

Global phosphoproteomic analysis identified key kinases regulating male meiosis in mouse.

Meiosis, a highly conserved process in organisms from fungi to mammals, is subjected to protein phosphorylation regulation. Due to the low abundance of phosphorylation, there is a lack of systemic characterization of phosphorylation regulation of meiosis in mammals. Using the phosphoproteomic approach, we profiled large-scale phosphoproteome of purified primary spermatocytes undergoing meiosis I, and identified 14,660 phosphorylation sites in 4419 phosphoproteins. Kinase-substrate phosphorylation network analysis followed by in vitro meiosis study showed that CDK9 was essential for meiosis progression to metaphase I and had enriched substrate phosphorylation sites in proteins involved in meiotic cell cycle. In addition, histones and epigenetic factors were found to be widely phosphorylated. Among those, HASPIN was found to be essential for male fertility. Haspin knockout led to misalignment of chromosomes, apoptosis of metaphase spermatocytes and a decreased number of sperm by deregulation of H3T3ph, chromosomal passenger complex (CPC) and spindle assembly checkpoint (SAC). The complicated protein phosphorylation and its important regulatory functions in meiosis indicated that in-depth studies of phosphorylation-mediated signaling could help us elucidate the mechanisms of meiosis.

Effects of proximal gastrectomy with narrow gastric tube anastomosis compared with total gastrectomy with Roux-en-Y anastomosis on upper gastric cancer.

OBJECTIVE: To investigate the clinical efficacy of proximal gastrectomy with narrow gastric tube anastomosis (PG-NGT) and total gastrectomy with Roux-en-Y anastomosis (TG-RY) for upper gastric cancer. MATERIALS AND METHODS: One hundred sixty-three upper gastric cancer patients were enrolled into the PG-NGT group and TG-RY group. The propensity score matching method was used to conduct a one-to-one match between the two groups with 38 patients in each group. RESULTS: Compared with the TG-RY group, the PG-NGT group had significantly (P < 0.05) shorter operation time, shorter hospital stay, and less intraoperative blood loss. The TG-RY group had significantly (P = 0.009) more lymph nodes dissected and greater (P = 0.014) total cost than the PG-NGT group, but no significant difference existed in the surgical cost between the two groups (P = 0.214). There was no significant (P > 0.05) difference in the incidence of anastomotic stenosis (10.5% vs. 13.1%) or the reflux esophagitis rate (8.6% vs. 9.1%) in the PG-NGT group and the TG-RY group. One year after surgery, the weight and hemoglobin and albumin levels in the PG-NGT group were significantly (P < 0.05) higher than those in the TG-RY group. CONCLUSIONS: PG-NGT may be better than TG-RY in improving patient weight loss and hemoglobin and albumin levels, without increasing the rate of anastomotic stenosis and reflux symptoms.