RGA1 regulates grain size, rice quality and seed germination in the small and round grain mutant srg5.

BACKGROUND: Generating elite rice varieties with high yield and superior quality is the main goal of rice breeding programs. Key agronomic traits, including grain size and seed germination characteristics, affect the final yield and quality of rice. The RGA1 gene, which encodes the α-subunit of rice G-protein, plays an important role in regulating rice architecture, seed size and abiotic stress responses. However, whether RGA1 is involved in the regulation of rice quality and seed germination traits is still unclear. RESULTS: In this study, a rice mutant small and round grain 5 (srg5), was identified in an EMS-induced rice mutant library. Systematic analysis of its major agronomic traits revealed that the srg5 mutant exhibited a semi-dwarf plant height with small and round grain and reduced panicle length. Analysis of the physicochemical properties of rice showed that the difference in rice eating and cooking quality (ECQ) between the srg5 mutant and its wild-type control was small, but the appearance quality was significantly improved. Interestingly, a significant suppression of rice seed germination and shoot growth was observed in the srg5 mutant, which was mainly related to the regulation of ABA metabolism. RGA1 was identified as the candidate gene for the srg5 mutant by BSA analysis. A SNP at the splice site of the first intron disrupted the normal splicing of the RGA1 transcript precursor, resulting in a premature stop codon. Additional linkage analysis confirmed that the target gene causing the srg5 mutant phenotype was RGA1. Finally, the introduction of the RGA1 mutant allele into two indica rice varieties also resulted in small and round rice grains with less chalkiness. CONCLUSIONS: These results indicate that RGA1 is not only involved in the control of rice architecture and grain size, but also in the regulation of rice quality and seed germination. This study sheds new light on the biological functions of RGA1, thereby providing valuable information for future systematic analysis of the G-protein pathway and its potential application in rice breeding programs.

Molecular patterns of microbial and metabolic interactions in septic patients with persistent lymphopenia.

BACKGROUND: Persistent lymphopenia can be regarded as an important index of acquired immune dysfunction in sepsis. Whether the specific immune factor changes in septic patients with lymphopenia and the correlation to gut microbiota and metabolites remain unclear. METHODS: This single-center prospective observation conducted lymphocyte subgroup analysis of blood samples and 16S rRNA gene amplicons sequencing and untargeted metabolomics analysis of fecal samples from 36 subjects with the persistent (≥3d) (n=21) and non-persistent lymphopenia (<3d) (n=15). RESULTS: The persistent lymphopenia showed higher the 28d mortality and 90d mortality, while significantly lower CD3+T/LY, CD3+T cells, CD3+CD4+T cells, CD3+CD8+T cells, Th1 cells, Th2 cells, CD45RA+Treg cells. The 16S rRNA results showed that Staphylococcus, Peptostreptococcus, Bulleidia, Leuconostoc were significant enriched in the persistent lymphopenia. The metabolomics analysis showed that α-Ketoisovaleric acid was increased and 7-DHCA, α-MCA, ß-MCA, HCA, LCA-3S, CA, UCA and Citramalic acid were decreased in the persistent lymphopenia. CONCLUSION: In the process of interaction between host receptors and gut microbiota in patients with persistent lymphopenia sepsis, with a significant reduction in gut microbiota diversity and bile acid metabolites. That can affect various inflammatory pathways of gut immune cells, causing immune dysfunction in the body, which may be one of the main causes of death.

Understanding the Poly (Triazine Imide) Crystals Formation Process: The Conversion from Heptazine to Triazine.

Poly (triazine imide) (PTI) generally obtained via ionothermal synthesis features extended π-conjugation and enhanced crystallinity. However, in-depth investigation of the polycondensation process for PTI is an onerous task due to multiple influencing factors and limited characterization techniques. Herein, to simplify the polymerization route and exclude non-essential factors, PTI was prepared by calcining only melamine and LiCl. This study aims to identify the pivotal role of LiCl in PTI formation, which can convert heptazine-based intermediates into more stable triazine-based PTI framework. Based on this discovery, we demonstrate the transformation process of the prepared samples from amorphous Bulk g-C3 N4 to regular PTI, and further prove that the reaction with LiCl causes disruption of heptazine covalent organic frameworks. Additionally, the PTI exhibits higher photocatalytic water splitting performance due to efficient charge carrier mobility and separation, as well as faster reaction kinetics. This discovery deepens understanding of the polycondensation process of PTI crystals and provides insights toward the rational design of crystalline carbon nitride-based semiconductors.

Photo-thermal Catalytic Hydrogenation of Halogenated Nitrobenzenes over Ni/P25 Catalyst.

As haloanilines (HANs) are important organic intermediates and fine chemicals, their preparation over non-noble-metal-based catalysts by catalytic hydrogenation has attracted wide attention. However, the reaction suffers from relatively harsh conditions. Herein, we found that a 3.5%Ni/P25 catalyst exhibited superior photo-thermal catalytic activity with a TOFs of 5207 h-1 for hydrogenation of p-chloronitrobenzene (p-CNB) to p-chloroaniline under a 300 W full spectrum, which was much higher than that of photo- and thermal catalysis alone. Moreover, the 3.5%Ni/P25 catalyst could be recycled 4 times and was effective for the hydrogenation of various halonitrobenzenes (HNBs) with superior selectivity. Furthermore, the kinetic research showed that the excellent catalytic performance could be attributed to the better activation and dissociation of H2 by photo-thermal catalysis and the hydrogenation of p-CNB obeyed the condensation routine by ionic hydrogenation over 3.5%Ni/P25.

Acoustic bright solitons propagation in bubbly liquids.

We study the propagation rules of acoustic bright solitons in bubble-containing media, as well as the strong anti-interference ability of acoustic solitons; and the effects of nonlinearity, dispersion, and dissipation on the dynamic properties of acoustic solitons are also analyzed. Based on the bubble-liquid mixture model, a lossy nonlinear Schrödinger equation is obtained. The analytical expression of the enveloped bright-acoustic solitons in the bubbly liquids is derived, which can accurately capture the propagation law of the acoustic bright solitons in the physical system, even if there is viscous loss in the medium. The dissipation-induced dynamics of acoustic solitons is studied through analytical and numerical methods, and the balancing effects of nonlinearity and dispersion in the propagation of bright solitons are analyzed. Furthermore, the particle nature and dynamic stability of bright-acoustic solitons in bubble-containing media are emphasized through fully elastic collisions between solitons moving in the same and opposite directions. This process obeys the energy and momentum conservation laws. After the collision, solitons can maintain their original amplitude, speed, and shape and continue to propagate undisturbed.

Physiological response and tolerance of Sesuvium portulacastrum L. to low temperature stress.

The plant Sesuvium portulacastrum L., commonly referred to as sea purslane, is a perennial halophytic species with significant potential for development in marine ecological restoration. However, its growth is limited in high-latitude regions with lower temperatures due to its subtropical nature. Furthermore, literature on its cold tolerance is scarce. This study, therefore, focused on sea purslane plants naturally overwintering in Ningbo (29°77'N), investigating their morphological, histological, rooting, and physiological responses to low temperatures (7 °C, 11 °C, 15 °C, and 19 °C). The findings indicated an escalation in cold damage severity with decreasing temperatures. At 7 °C, the plants failed to root and subsequently perished. In contrast, at 11 °C, root systems developed, while at 15 °C and 19 °C, the plants exhibited robust growth, outperforming the 11 °C group in terms of leaf number and root length significantly (P < 0.05). Histological analyses showed a marked reduction in leaf thickness under cold stress (P < 0.05), with disorganized leaf structure observed in the 7 °C group, whereas it remained stable at higher temperatures. No root primordia were evident in the vascular cambium of the 7 and 11 °C groups, in contrast to the 15 and 19 °C groups. Total chlorophyll content decreased with temperature, following the order: 19 °C > 15 °C > 11 °C > 7 °C. Notably, ascorbic acid levels were significantly higher in the 7 and 11 °C groups than in the 15 and 19 °C groups. Additionally, the proline concentration in the 7 °C group was approximately fourfold higher than in the 19 °C group. Activities of antioxidant enzymes-superoxide dismutase, peroxidase, and catalase-were significantly elevated in the 7 and 11 °C groups compared to the 15 and 19 °C groups. Moreover, the malondialdehyde content in the 7 °C group (36.63 ± 1.75 nmol/g) was significantly higher, about 5.5 and 9.6 times, compared to the 15 °C and 19 °C groups, respectively. In summary, 7 °C is a critical threshold for sea purslane stem segments; below this temperature, cellular homeostasis is disrupted, leading to an excessive accumulation of lipid peroxides and subsequent death due to an inability to neutralize excess reactive oxygen species. At 11 °C, although photosynthesis is impaired, self-protective mechanisms such as enhanced antioxidative systems and osmoregulation are activated. However, root development is compromised, resulting in stunted growth. These results contribute to expanding the geographic distribution of sea purslane and provide a theoretical basis for its ecological restoration in high-latitude mariculture. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01429-6.

[Clinicians' Practice and Opinions on Sedation Therapy in End-Stage Patients].

Objective To investigate clinicians' practice and opinions on sedation therapy in end-stage patients at Peking Union Medical College Hospital. Methods From August,2022 to April,2023,an online questionnaire survey was conducted among clinicians involved in end-stage patient management. Results A total of 205 questionnaires were distributed,with an effective response rate of 56.1%.Among the clinicians,55.7% of them had experience of applying sedation therapy in end-stage patients;85.2% of clinicians believed that sedation could relieve the suffering of terminal patients from physical refractory symptoms;75.7% of clinicians considered that sedation therapy could be used to relieve agony from psycho-existential distress.Most clinicians had concerns about sedation therapy due to the lack of legal support(86.1%)and the lack of understanding of patients or families(59.1%).The majority (90.4%) of clinicians were willing to receive training on palliative sedation. Conclusions A majority of clinicians agree that sedation therapy could relieve the physical distress and psycho-existential distress in end-stage patients.However,most clinicians have concerns about the application of sedation therapy due to the lack of legal support.It is necessary to enhance the training on palliative sedation.

SARS-CoV-2 envelope protein triggers depression-like behaviors and dysosmia via TLR2-mediated neuroinflammation in mice.

BACKGROUND: Depression and dysosmia have been regarded as primary neurological symptoms in COVID-19 patients, the mechanism of which remains unclear. Current studies have demonstrated that the SARS-CoV-2 envelope (E) protein is a pro-inflammatory factor sensed by Toll-like receptor 2 (TLR2), suggesting the pathological feature of E protein is independent of viral infection. In this study, we aim to ascertain the role of E protein in depression, dysosmia and associated neuroinflammation in the central nervous system (CNS). METHODS: Depression-like behaviors and olfactory function were observed in both female and male mice receiving intracisternal injection of E protein. Immunohistochemistry was applied in conjunction with RT-PCR to evaluate glial activation, blood-brain barrier status and mediators synthesis in the cortex, hippocampus and olfactory bulb. TLR2 was pharmacologically blocked to determine its role in E protein-related depression-like behaviors and dysosmia in mice. RESULTS: Intracisternal injection of E protein evoked depression-like behaviors and dysosmia in both female and male mice. Immunohistochemistry suggested that the E protein upregulated IBA1 and GFAP in the cortex, hippocampus and olfactory bulb, while ZO-1 was downregulated. Moreover, IL-1ß, TNF-α, IL-6, CCL2, MMP2 and CSF1 were upregulated in both cortex and hippocampus, whereas IL-1ß, IL-6 and CCL2 were upregulated in the olfactory bulb. Furtherly, inhibiting microglia, rather than astrocytes, alleviated depression-like behaviors and dysosmia induced by E protein. Finally, RT-PCR and immunohistochemistry suggested that TLR2 was upregulated in the cortex, hippocampus and olfactory bulb, the blocking of which mitigated depression-like behaviors and dysosmia induced by E protein. CONCLUSIONS: Our study demonstrates that envelope protein could directly induce depression-like behaviors, dysosmia, and obvious neuroinflammation in CNS. TLR2 mediated depression-like behaviors and dysosmia induced by envelope protein, which could serve as a promising therapeutic target for neurological manifestation in COVID-19 patients.

3D Printing of Robust High-Performance Conducting Polymer Hydrogel-Based Electrical Bioadhesive Interface for Soft Bioelectronics.

Electrical bioadhesive interface (EBI), especially conducting polymer hydrogel (CPH)-based EBI, exhibits promising potential applications in various fields, including biomedical devices, neural interfaces, and wearable devices. However, current fabrication techniques of CPH-based EBI mostly focus on conventional methods such as direct casting, injection, and molding, which remains a lingering challenge for further pushing them toward customized practical bioelectronic applications and commercialization. Herein, 3D printable high-performance CPH-based EBI precursor inks are developed through composite engineering of PEDOT:PSS and adhesive ionic macromolecular dopants within tough hydrogel matrices (PVA). Such inks allow the facile fabrication of high-resolution and programmable patterned EBI through 3D printing. Upon successive freeze-thawing, the as-printed PEDOT:PSS-based EBI simultaneously exhibits high conductivity of 1.2 S m-1 , low interfacial impedance of 20 Ω, high stretchability of 349%, superior toughness of 109 kJ m-3 , and satisfactory adhesion to various materials. Enabled by these advantageous properties and excellent printability, the facile and continuous manufacturing of EBI-based skin electrodes is further demonstrated via 3D printing, and the fabricated electrodes display excellent ECG and EMG signal recording capability superior to commercial products. This work may provide a new avenue for rational design and fabrication of next-generation EBI for soft bioelectronics, further advancing seamless human-machine integration.

Oral microbiota disorder in GC patients revealed by 2b-RAD-M.

BACKGROUND: Microbiota alterations are linked with gastric cancer (GC). However, the relationship between the oral microbiota (especially oral fungi) and GC is not known. In this study, we aimed to apply 2b-RAD sequencing for Microbiome (2b-RAD-M) to characterize the oral microbiota in patients with GC. METHODS: We performed 2b-RAD-M analysis on the saliva and tongue coating of GC patients and healthy controls. We carried out diversity, relative abundance, and composition analyses of saliva and tongue coating bacteria and fungi in the two groups. In addition, indicator analysis, the Gini index, and the mean decrease accuracy were used to identify oral fungal indicators of GC. RESULTS: In this study, fungal imbalance in the saliva and tongue coating was observed in the GC group. At the species level, enriched Malassezia globosa (M. globosa) and decreased Saccharomyces cerevisiae (S. cerevisiae) were observed in saliva and tongue coating samples of the GC group. Random forest analysis indicated that M. globosa in saliva and tongue coating samples could serve as biomarkers to diagnose GC. The Gini index and mean decreases in accuracy for M. globosa in saliva and tongue coating samples were the largest. In addition, M. globosa in saliva and tongue coating samples classified GC from the control with areas under the receiver operating curve (AUCs) of 0.976 and 0.846, respectively. Further ecological analysis revealed correlations between oral bacteria and fungi. CONCLUSION: For the first time, our data suggested that changes in oral fungi between GC patients and controls may help deepen our understanding of the complex spectrum of the different microbiotas involved in GC development. Although the cohort size was small, this study is the first to use 2b-RAD-M to reveal that oral M. globosa can be a fungal biomarker for detecting GC.

Brassinosteroids regulate rice seed germination through the BZR1-RAmy3D transcriptional module.

Seed dormancy and germination, two physiological processes unique to seed-bearing plants, are critical for plant growth and crop production. The phytohormone brassinosteroid (BR) regulates many aspects of plant growth and development, including seed germination. The molecular mechanisms underlying BR control of rice (Oryza sativa) seed germination are mostly unknown. We investigated the molecular regulatory cascade of BR in promoting rice seed germination and post-germination growth. Physiological assays indicated that blocking BR signaling, including introducing defects into the BR-insensitive 1 (BRI1) receptor or overexpressing the glycogen synthase kinase 2 (GSK2) kinase delayed seed germination and suppressed embryo growth. Our results also indicated that brassinazole-resistant 1 (BZR1) is the key downstream transcription factor that mediates BR regulation of seed germination by binding to the alpha-Amylase 3D (RAmy3D) promoter, which affects α-amylase expression and activity and the degradation of starch in the endosperm. The BZR1-RAmy3D module functions independently from the established Gibberellin MYB-alpha-amylase 1A (RAmy1A) module of the gibberellin (GA) pathway. We demonstrate that the BZR1-RAmy3D module also functions in embryo-related tissues. Moreover, RNA-sequencing (RNA-seq) analysis identified more potential BZR1-responsive genes, including those involved in starch and sucrose metabolism. Our study successfully identified the role of the BZR1-RAmy3D transcriptional module in regulating rice seed germination.

Photoinduced Metal- and Photosensitizer-Free Decarbonylative C-H Alkylation of Cyclic Sulfamidate Imines.

Photoinduced decarbonylative C-C bond formation with readily accessible aldehydes as alkyl sources is described. This protocol provides a sustainable alternative for the effective construction of diverse valuable 4-alkylated sulfonyl ketimines under metal- and photosensitizer-free conditions. Significantly, in this reaction, air serves as the green oxidant, and cyclic sulfamidate imines play a dual role of substrate and photocatalyst, thus affording a concise reaction system for C-H alkylation of cyclic sulfamidate imines.

Intraoperative Blood Pressure Lability Acts as a Key Mediator in the Impacts of Goal-Directed Fluid Therapy on Postoperative Complications in Patients Undergoing Major Spine Surgery.

Objective Although goal-directed fluid therapy (GDFT) has been proven to be effective in reducing the incidence of postoperative complications, the underlying mechanisms remain unknown. The aim of this study was to examine the mediating role of intraoperative hemodynamic lability in the association between GDFT and the incidence of postoperative complications. We further tested the role of this mediation effect using mean arterial pressure, a hemodynamic indicator. Methods This secondary analysis used the dataset of a completed nonrandomized controlled study to investigate the effect of GDFT on the incidence of postoperative complications in patients undergoing posterior spine arthrodesis. We used a simple mediation model to test whether there was a mediation effect of average real variability between the association of GDFT and postoperative complications. We conducted mediation analysis using the mediation package in R (version 3.1.2), based on 5,000 bootstrapped samples, adjusting for covariates. Results Among the 300 patients in the study, 40% (120/300) developed postoperative complications within 30 days. GDFT was associated with fewer 30-day postoperative complications after adjustment for confounders (odds ratio: 0.460, 95% CI: 0.278, 0.761; P = 0.003). The total effect of GDFT on postoperative complications was -0.18 (95% CI: -0.28, -0.07; P < 0.01). The average causal mediation effect was -0.08 (95% CI: -0.15, -0.04; P < 0.01). The average direct effect was -0.09 (95% CI: -0.20, 0.03; P = 0.17). The proportion mediated was 49.9% (95% CI: 18.3%, 140.0%). Conclusions The intraoperative blood pressure lability mediates the relationship between GDFT and the incidence of postoperative complications. Future research is needed to clarify whether actively reducing intraoperative blood pressure lability can prevent postoperative complications.

[Standard Process for Palliative Sedation in Peking Union Medical College Hospital].

End-stage patients experience unbearable pain because of refractory symptoms.Palliative sedation is a form of palliative care which relieves patients' agony by lowering their consciousness.Standard palliative sedation can help patients die with dignity.It is distinct from euthanasia and does not alter the survival of patients.Sufficient palliative care is the premise of palliative sedation.Repeated and detailed clinical evaluation,as well as multidisciplinary involvement,is necessary for the standardized implementation of palliative sedation.Here,we proposed the standard process and specifications of palliative sedation in Peking Union Medical College Hospital.Furthermore,we reported a case of palliative sedation for an advanced cancer patient with refractory delirium and living pain to demonstrate its application in clinical practice.

Preoperative Anxiety in Chinese Adult Patients Undergoing Elective Surgeries: A Multicenter Cross-Sectional Study.

BACKGROUND: Preoperative anxiety is associated with increased use of anesthetics and poorer postoperative outcomes. However, the prevalence of preoperative anxiety has not been characterized in Chinese patients. In this study, we aimed to estimate the overall prevalence of preoperative anxiety in Chinese adult patients and to explore the sociodemographic and clinical factors associated with preoperative anxiety in China. METHODS: This study was a multicenter cross-sectional study conducted at 32 tertiary referral centers in China from September 1 to October 31, 2020. Adult patients scheduled for elective surgery were evaluated by the 7-item Perioperative Anxiety Scale (PAS-7) for preoperative anxiety after entrance to the operating zone. RESULTS: A total of 5191 patients were recruited, and 5018 of them were analyzed. The prevalence of preoperative anxiety measured by PAS-7 was 15.8% (95% CI 14.8 to 16.9%). Multivariable analyses showed female sex, younger age, non-retired, first in a lifetime surgery, surgery of higher risk, and poorer preoperative sleep were associated with higher prevalence of preoperative anxiety. CONCLUSIONS: Preoperative anxiety was relatively common (prevalence of 15.8%) among adult Chinese patients undergoing elective surgeries. Further studies are needed using suitable assessment tools to better characterize preoperative anxiety, and additional focus should be placed on perioperative education and intervention, especially in primary hospitals. TRIAL REGISTRATION: This study was registered prospectively at www.chictr.org.cn (ChiCTR1900027639) on November 22, 2019.

Point Cloud Geometry Compression Based on Multi-Layer Residual Structure.

Point cloud data are extensively used in various applications, such as autonomous driving and augmented reality since it can provide both detailed and realistic depictions of 3D scenes or objects. Meanwhile, 3D point clouds generally occupy a large amount of storage space that is a big burden for efficient communication. However, it is difficult to efficiently compress such sparse, disordered, non-uniform and high dimensional data. Therefore, this work proposes a novel deep-learning framework for point cloud geometric compression based on an autoencoder architecture. Specifically, a multi-layer residual module is designed on a sparse convolution-based autoencoders that progressively down-samples the input point clouds and reconstructs the point clouds in a hierarchically way. It effectively constrains the accuracy of the sampling process at the encoder side, which significantly preserves the feature information with a decrease in the data volume. Compared with the state-of-the-art geometry-based point cloud compression (G-PCC) schemes, our approach obtains more than 70-90% BD-Rate gain on an object point cloud dataset and achieves a better point cloud reconstruction quality. Additionally, compared to the state-of-the-art PCGCv2, we achieve an average gain of about 10% in BD-Rate.

Improving rice eating and cooking quality by coordinated expression of the major starch synthesis-related genes, SSII and Wx, in endosperm.

KEY MESSAGE: Coordinated regulation of amylose and amylopectin synthesis via manipulation of SSII-2, SSII-3 and Wx expression in endosperm can improve rice eating and cooking quality. With increasing rice consumption worldwide, many researchers are working to increase the yield and improve grain quality, especially eating and cooking quality (ECQ). The rice ECQ is mainly controlled by the expression of starch synthesis-related genes (SSRGs) in endosperm. Although the Wx and SSII-3/SSIIa/ALK genes, two major SSRGs, have been manipulated to improve rice ECQ via various breeding approaches, new methods to further improve ECQ are desired. In our previous study, we enhanced rice ECQ by knocking down SSII-2 expression in the japonica Nipponbare cultivar (carrying the Wxb allele) via RNA interference. Herein, the SSII-2 RNAi was introduced into two Nipponbare-derived near-isogenic lines (NILs), Nip(Wxa) and Nip(wx), carrying Wxa and wx alleles respond for high and no amylose levels, respectively. Analysis of physicochemical properties revealed that the improved grain quality of SSII-2 RNAi transgenic lines was achieved by coordinated downregulating the expression of SSII-2, SSII-3 and Wx. To further confirm this conclusion, we generated ssii-2, ssii-3 and ssii-2ssii-3 mutants via CRISPR/Cas9 technique. The amylopectin structure of the resulting ssii-2sii-3 mutants was similar to that in SSII-2 RNAi transgenic lines, and the absence of SSII-2 decreased the amylose content, gelatinisation temperature and rapid visco-analyser profile, indicating essential roles for SSII-2 in the regulation of amylopectin biosynthesis and amylose content in rice endosperm. The effect of SSII-2 was seen only when the activity of SSII-3 was very low or lacking. Our study provides novel approaches and valuable germplasm resources for improving ECQ via plant breeding.

Suppression of TLR4-MyD88 signaling pathway attenuated chronic mechanical pain in a rat model of endometriosis.

BACKGROUND: As a classic innate immunity pathway, Toll-like receptor 4 (TLR4) signaling has been intensively investigated for its function of pathogen recognition. The receptor is located not only on immune cells but also on sensory neurons and spinal glia. Recent studies revealed the involvement of neuronal TLR4 in different types of pain. However, the specific role of TLR4 signaling in the pain symptom of endometriosis (EM) remains obscure. METHODS: The rat endometriosis model was established by transplanting uterine horn tissue into gastrocnemius. Western blotting and/or immunofluorescent staining were applied to detect high mobility group box 1 (HMGB1), TLR4, myeloid differentiation factor-88 adaptor protein (MyD88), and nuclear factor kappa-B-p65 (NF-κB-p65) expression, as well as the activation of astrocyte and microglia. The antagonist of TLR4 (LPS-RS-Ultra, LRU) and MyD88 homodimerization inhibitory peptide (MIP) were intrathecally administrated to assess the behavioral effects of blocking TLR4 signaling on endometriosis-related pain. RESULTS: Mechanical hyperalgesia was observed at the graft site, while HMGB1 was upregulated in the implanted uterine tissue, dorsal root ganglion (DRG), and spinal dorsal horn (SDH). Compared with sham group, upregulated TLR4, MyD88, and phosphorylated NF-κB-p65 were detected in the DRG and SDH in EM rats. The activation of astrocytes and microglia in the SDH was also confirmed in EM rats. Intrathecal application of LRU and MIP alleviated mechanical pain on the graft site of EM rats, with decreased phosphorylation of NF-κB-p65 in the DRG and reduced activation of glia in the SDH. CONCLUSIONS: HMGB1-TLR4-MyD88 signaling pathway in the DRG and SDH may involve in endometriosis-related hyperpathia. Blockade of TLR4 and MyD88 might serve as a potential treatment for pain in endometriosis.

Design, synthesis, and biological evaluation of cyano-substituted 2,4-diarylaminopyrimidines as potent JAK3 inhibitors for the treatment of B-cell lymphoma.

A series of cyano-substituted 2,4-diarylaminopyrimidines was designed and synthesized as potent non-covalent JAK3 inhibitors. Among the derivatives synthesized, 9o (IC50 = 22.86 nM), 9 k (IC50 = 21.58 nM), and 9j (IC50 = 20.66 nM) demonstrated inhibitory potencies against JAK3 similar to the known JAK3 inhibitor tofacitinib (IC50 = 20.10 nM). Moreover, 9o displayed potent anti-proliferative activities against Raji and Ramos cells, with IC50 values of 0.9255 µM and 1.405 µM, respectively. In addition, 9o demonstrated low toxicity in normal HBE (human bronchial epithelial cells, IC50 > 10 µΜ) and L-02 (human liver cells, IC50 = 3.104 µΜ) cells. Analysis of the mode of action by flow cytometry indicated that 9o effectively arrested Raji cells at the G2/M phase. Taken together, these results suggested that 9o might be a promising candidate for development as a potential treatment for B-cell lymphoma.

Perioperative and oncological outcomes following minimally invasive versus open pancreaticoduodenectomy for pancreatic duct adenocarcinoma.

BACKGROUND: The outcomes of minimally invasive pancreaticoduodenectomy have not been adequately compared with those of open pancreaticoduodenectomy in patients with pancreatic ductal adenocarcinoma. We performed a meta-analysis to compare the perioperative and oncological outcomes of these two pancreaticoduodenectomy procedures specifically in patients with pancreatic ductal adenocarcinoma. METHODS: Before this study was initiated, a specific protocol was designed and has been registered in PROSEPRO (ID: CRD42020149438). Using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, PubMed, EMBASE, Web of Science, Cochrane Central Register, and ClinicalTrials.gov databases were systematically searched for studies published between January 1994 and October 2019. Overall survival, disease-free survival, and time to commencing adjuvant chemotherapy were the primary endpoint measurements, whereas perioperative and short-term outcomes were the secondary endpoints. RESULTS: The final analysis included 9 retrospective cohorts comprising 11,242 patients (1377 who underwent minimally invasive pancreaticoduodenectomy and 9865 who underwent open pancreaticoduodenectomy). There were no significant differences in the patients' overall survival, operative time, postoperative complications, 30-day mortality, rate of vein resection, number of harvested lymph nodes, or rate of positive lymph nodes between the two approaches. However, disease-free survival, time to starting adjuvant chemotherapy, length of hospital stay, and rate of negative margins in patients who underwent minimally invasive pancreaticoduodenectomy showed improvements relative to those in patients who underwent open surgery. CONCLUSIONS: Minimally invasive pancreaticoduodenectomy provides similar or even improved perioperative, short-term, and long-term oncological outcomes when compared with open pancreaticoduodenectomy for patients with pancreatic ductal adenocarcinoma.