P75NTR+CD64+ neutrophils promote sepsis-induced acute lung injury.

Patients suffering from sepsis-induced acute lung injury (ALI) exhibit a high mortality rate, and their prognosis is closely associated with infiltration of neutrophils into the lungs. In this study, we found a significant elevation of CD64+ neutrophils, which highly expressed p75 neurotrophin receptor (p75NTR) in peripheral blood of mice and patients with sepsis-induced ALI. p75NTR+CD64+ neutrophils were also abundantly expressed in the lung of ALI mice induced by lipopolysaccharide. Conditional knock-out of the myeloid lineage's p75NTR gene improved the survival rates, attenuated lung tissue inflammation, reduced neutrophil infiltration and enhanced the phagocytic functions of CD64+ neutrophils. In vitro, p75NTR+CD64+ neutrophils exhibited an upregulation and compromised phagocytic activity in blood samples of ALI patients. Blocking p75NTR activity by soluble p75NTR extracellular domain peptide (p75ECD-Fc) boosted CD64+ neutrophil phagocytic activity and reduced inflammatory cytokine production via activation of the NF-κB pathway. The findings strongly indicate that p75NTR+CD64+ neutrophils are a novel pathogenic neutrophil subpopulation promoting sepsis-induced ALI.

Indoxyl sulphate-TNFα axis mediates uremic encephalopathy in rodent acute kidney injury.

Acute kidney injury (AKI) is often accompanied by uremic encephalopathy resulting from accumulation of uremic toxins in brain possibly due to impaired blood-brain barrier (BBB) function. Anionic uremic toxins are substrates or inhibitors of organic anionic transporters (OATs). In this study we investigated the CNS behaviors and expression/function of BBB OAT3 in AKI rats and mice, which received intraperitoneal injection of cisplatin 8 and 20 mg/kg, respectively. We showed that cisplatin treatment significantly inhibited the expressions of OAT3, synaptophysin and microtubule-associated protein 2 (MAP2), impaired locomotor and exploration activities, and increased accumulation of uremic toxins in the brain of AKI rats and mice. In vitro studies showed that uremic toxins neither alter OAT3 expression in human cerebral microvascular endothelial cells, nor synaptophysin and MAP2 expressions in human neuroblastoma (SH-SY5Y) cells. In contrast, tumour necrosis factor alpha (TNFα) and the conditioned medium (CM) from RAW264.7 cells treated with indoxyl sulfate (IS) significantly impaired OAT3 expression. TNFα and CM from IS-treated BV-2 cells also inhibited synaptophysin and MAP2 expressions in SH-SY5Y cells. The alterations caused by TNFα and CMs in vitro, and by AKI and TNFα in vivo were abolished by infliximab, a monoclonal antibody designed to intercept and neutralize TNFα, suggesting that AKI impaired the expressions of OAT3, synaptophysin and MAP2 in the brain via IS-induced TNFα release from macrophages or microglia (termed as IS-TNFα axis). Treatment of mice with TNFα (0.5 mg·kg-1·d-1, i.p. for 3 days) significantly increased p-p65 expression and reduced the expressions of Nrf2 and HO-1. Inhibiting NF-κB pathway, silencing p65, or activating Nrf2 and HO-1 obviously attenuated TNFα-induced downregulation of OAT3, synaptophysin and MAP2 expressions. Significantly increased p-p65 and decreased Nrf2 and HO-1 protein levels were also detected in brain of AKI mice and rats. We conclude that AKI inhibits the expressions of OAT3, synaptophysin and MAP2 due to IS-induced TNFα release from macrophages or microglia. TNFα impairs the expressions of OAT3, synaptophysin and MAP2 partly via activating NF-κB pathway and inhibiting Nrf2-HO-1 pathway.

Curcumin regulates autophagy through SIRT3-SOD2-ROS signaling pathway to improve quadriceps femoris muscle atrophy in KOA rat model.

Knee osteoarthritis (KOA) usually leads to quadriceps femoris atrophy, which in turn can further aggravate the progression of KOA. Curcumin (CUR) has anti-inflammatory and antioxidant effects and has been shown to be a protective agent for skeletal muscle. CUR has been shown to have a protective effect on skeletal muscle. However, there are no studies related to whether CUR improves KOA-induced quadriceps femoris muscle atrophy. We established a model of KOA in rats. Rats in the experimental group were fed CUR for 5 weeks. Changes in autophagy levels, reactive oxygen species (ROS) levels, and changes in the expression of the Sirutin3 (SIRT3)-superoxide dismutase 2 (SOD2) pathway were detected in the quadriceps femoris muscle of rats. KOA led to quadriceps femoris muscle atrophy, in which autophagy was induced and ROS levels were increased. CUR increased SIRT3 expression, decreased SOD2 acetylation and ROS levels, inhibited the over-activation of autophagy, thereby alleviating quadriceps femoris muscle atrophy and improving KOA. CUR has a protective effect against quadriceps femoris muscle atrophy, and KOA is alleviated after improvement of quadriceps femoris muscle atrophy, with the possible mechanism being the reduction of ROS-induced autophagy via the SIRT3-SOD2 pathway.

Precirrhotic Primary Biliary Cholangitis with Portal Hypertension: Bile Duct Injury Correlate.

Background/Aims: : The histological characteristics and natural history of precirrhotic primary biliary cholangitis (PBC) with portal hypertension (PH) are unclear. Our aim was to clarify the prevalence, risk factors, and histological characteristics of precirrhotic PBC patients with PH. Methods: : This retrospective study compared the clinical features, histological characteristics, and response to ursodeoxycholic acid (UDCA) between the PH and non-PH groups of precirrhotic PBC patients. Results: : Out of 165 precirrhotic PBC patients, 40 (24.2%) also had PH. According to histological stage 1, 2 and 3 disease, 5.3% (1/19), 17.3% (17/98), and 45.8% (22/48) of patients also had PH, respectively. Precirrhotic PBC with PH was significantly positively correlated with bile duct loss, degree of cytokeratin 7 positivity, and degree of fibrosis in the portal area, but significantly negatively correlated with lymphoid follicular aggregation. Compared to the non-PH group, patients in the PH group showed a higher prevalence of obliterative portal venopathy, incomplete septal fibrosis, portal tract abnormalities and non-zonal sinusoidal dilatation (p<0.05). In addition, patients with PH were more likely to present with symptoms of jaundice, ascites, epigastric discomfort, a poorer response to UDCA, and more decompensation events (p<0.05). High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values were risk factors for precirrhotic PBC with PH. Conclusions: : Approximately 24.2% of precirrhotic PBC patients have PH, which is histologically related to the injury of bile ducts. High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values are associated with increased risk of precirrhotic PBC with PH.

Series of Viologen-Based Metal-Organic Polyhedra with Photo/Electrochromic Behavior for Inkless Printing and UV Detection.

The fabrication of molecular crystalline materials with fast, multistimuli-responsive behavior and the construction of the corresponding structure-activity relationship are of extraordinary significance for the development of smart materials. In this context, three multistimuli-responsive functional metal-organic polyhedra (MOP), {[Dy2(bcbp)3(NO3)1.5(H2O)7]·Cl4.2·(NO3)0.3·H2O}n (1), {[Dy2(bcbp)4(H2O)8]Cl6}n (2), and {[Eu2(bcbp)4(H2O)10]Cl6·H2O}n (3; bcbp = 1,1'-bis(4-carboxyphenyl)-4,4'-bipyridinium), were successfully prepared and characterized. All of the compounds exhibit rapid and reversible photochromic and electrochromic dual-responsive behaviors. Furthermore, benefiting from the well-defined crystal structure and different responsive behaviors, the photoinduced electron transfer (PIET) process and structure-activity relationship were explored. In addition, considering the excellent photochromic performance, function filter paper and smart organic glass were successfully prepared and used for ink-free printing and UV light detection.

Chelativorans salis sp. nov., a slightly halophilic bacterium isolated from an enrichment system with saline lake sediment.

A Gram-stain-negative, non-motile, and slightly halophilic alphaproteobacterium, designated strain EGI FJ00035T, was isolated from enrichment sediment samples of a saline lake in Xinjiang Uygur Autonomous Region, PR China. The taxonomic position of the isolate was determined using the polyphasic taxonomic and phylogenomic analyses. Phylogenetic analysis based on the 16S rRNA gene sequences indicated that strain EGI FJ00035T formed a distinct clade with 'Chelativorans alearense' UJN715 and 'Chelativorans xinjiangense' lm93 with sequence similarities of 98.44 and 98.22 %, respectively, while sharing less than 96.7 % with other valid type strains. The novel isolate could be distinguished from other species of the genus Chelativorans by its distinct phenotypic, physiological, and genotypic characteristics. Optimal growth of strain EGI FJ00035T occurred on marine agar 2216 at pH 7.0 and 30 °C. The major respiratory quinone was Q-10, while the major fatty acids (>5 %) were C19 : 0 cyclo ω8c, summed feature 8 (C17 : 1 ω6c and/or C17 : 1 ω7c), C16 : 0, C18 : 0, and iso-C17 : 0. The detected polar lipids included diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, unidentified aminophospholipids, unidentified glycolipids, and an unidentified lipid. Based on its genome sequence, the G+C content of strain EGI FJ00035T was 63.2 mol%. The average nucleotide identity, average amino acid identity, and digital DNA-DNA hybridization values of strain EGI FJ00035T against related members of the genus Chelativorans were below the thresholds for delineation of a novel species. According our polyphasic taxonomic data, strain EGI FJ00035T represents a new species of the genus Chelativorans, for which the name Chelativorans salis sp. nov. is proposed. The type strain of the proposed novel isolate is EGI FJ00035T (=KCTC 92251T=CGMCC 1.19480T).

Effect of the configuration mixing on the polarization and angular distribution of x-ray line emissions following electron-impact excitation of Ne-like ions.

We present a systematic theoretical study on the angular distribution and linear polarization of x-ray line emissions of neon-like ions following the electron-impact excitation from the ground state to the excited levels [(2p5)1/23d3/2]J=1, [(2p5)3/23d5/2]J=1, [(2p5)3/23d3/2]J=1, and [(2p5)1/23s]J=1. The cross sections are calculated by using the flexible atomic code under configuration-interaction plus many-body perturbation theory method. The angular distribution and linear polarization are obtained based on density matrix theory. Emphasis has been placed on the effect of the configuration mixing on the angular distribution and polarization. It has been proved that the strong mixing of configuration [(2p5)3/23d3/2]J=1 with configuration [(2p5)1/23s]J=1 can result in the abrupt change of Z-dependence of angular distribution and polarization. It indicates that angular distribution and polarization can be expected to serve as a tool for investigation of configuration mixing effect.

[The Polymorphism Analysis of HLA Class II Alleles Based on Next-Generation Sequencing and Prevention Strategy for Allele Dropout].

OBJECTIVE: To investigate the accuracy of next-generation sequencing technology (NGS) in detecting the polymorphisms of HLA-DRB1, DQB1, DQA1, DRB3, DRB4, DRB5, DPA1 and DPB1 alleles in randomly-selected unrelated healthy individuals from Shenzhen Han population, investigate the potential reason for HLA-DRB1 allele dropout in routine NGS, and establish an internal quality control system. METHODS: NGS-based HLA class II genotyping was performed on 1 012 samples using the MiSeqDxTM platform. The suspected missed alleles indicated by the quality control software and HLA-DRB1 homozygotes were confirmed by PCR-SSOP or PCR-SBT methods. RESULTS: A total of 139 alleles were detected, including HLA-DRB1(45), DRB3(7), DRB4(5), DRB5(7), DQA1(17), DQB1(21), DPA1(10) and DPB1(27). HLA-DRB1*09:01(17.09%),15:01(10.72%); DRB3*02:02(25.99%),03:01(10.18%); DRB4*01:03(36.46%); DRB5*01:01(15.42%); DQA1*01:02(20.01%),03:02(17.19%); DQB1*03:01(19.47%),03:03(17.98%), 05:02(11.66%), 06:01(10.67%); DPA1*02:02(54.45%), 01:03(31.18%) and DPB1*05:01(39.13%), 02:01(16.90%) alleles were the most common alleles in Shenzhen Han population (frequencies >10%). There was no statistical difference between the gene frequencies of HLA-DRB1 and DQB1 loci in our study. The HLA Common and Well-Documented Alleles in China (CWD2.4) (χ2=12.68, P >0.05). 94 cases of HLA-DRB1 homozygous samples detected by NGS were retested by PCR-SSOP or SBT method, and one case of allele dropout at HLA-DRB1 locus was found. SBT method confirmed that the allele of DRB1*04:03 was missed. The laboratory internal quality control system was established. Two cases of new alleles were detected and named by WHO Nomenclature Committee for Factors of the HLA System. CONCLUSION: The HLA genotyping results based on NGS showed a significantly lower ambiguity rate. The HLA class II alleles exhibit genetic polymorphism in the Han population of unrelated healthy individuals in Shenzhen. The independent method based on NGS in clinical histocompatibility testing has limitations and requires internal quality control strategies to avoid allele-dropout events.

Losartan ameliorates renal fibrosis by inhibiting tumor necrosis factor signal pathway / Losartán mejora la fibrosis renal al inhibir la vía de señalización del factor de necrosis tumoral

Losartan is widely used in the treatment of chronic kidney disease (CKD) and has achieved good clinical efficacy, but its exact mechanism is not clear. We performed high-throughput sequencing (HTS) technology to screen the potential target of losartan in treating CKD. According to the HTS results, we found that the tumor necrosis factor (TNF) signal pathway was enriched. Therefore, we conducted in vivo and in vitro experiments to verify it. We found that TNF signal pathway was activated in both unilateral ureteral obstruction (UUO) rats and human proximal renal tubular epithelial cells (HK-2) treated with transforming growth factor-β1 (TGF-β1), while losartan can significantly inhibit TNF signal pathway as well as the expression of fibrosis related genes (such as COL-1, α-SMA and Vimentin). These data suggest that losartan may ameliorate renal fibrosis through modulating the TNF pathway.(AU)

El Losartán es ampliamente utilizado en el tratamiento de la enfermedad renal crónica (CKD) y ha logrado buenos resultados clínicos, pero su mecanismo exacto aún no está claro. Utilizamos la técnica de secuenciación de alto rendimiento (HTS) para detectar posibles dianas de losartán para el tratamiento de la CKD. Según los resultados de HTS, encontramos un enriquecimiento de la vía de señalización del factor de necrosis tumoral (TNF). Así, realizamos experimentos in vivo e in vitro para verificar esto. Encontramos que, tanto en ratas con obstrucción ureteral unilateral (uuo) como en células epiteliales tubulares renales proximal humanas (HK-2) tratadas con factor de crecimiento transformador β1 (TGF-β1), se activó la vía de señalización del TNF. El losartán inhibe significativamente la expresión de las vías de señalización del TNF y genes relacionados con la fibrosis, como COL-1, α-SMA y vicentin. Estos datos sugieren que el losartán puede mejorar la fibrosis renal regulando la vía del TNF.(AU)

Human embryonic stem cell-derived mesenchymal stromal cells suppress inflammation in mouse models of rheumatoid arthritis and lung fibrosis by regulating T-cell function.

BACKGROUND AIMS: Rheumatoid arthritis (RA) is characterized by an overactive immune system, with limited treatment options beyond immunosuppressive drugs or biological response modifiers. Human embryonic stem cell-derived mesenchymal stromal cells (hESC-MSCs) represent a novel alternative, possessing diverse immunomodulatory effects. In this study, we aimed to elucidate the therapeutic effects and underlying mechanisms of hESC-MSCs in treating RA. METHODS: MSC-like cells were differentiated from hESC (hESC-MSCs) and cultured in vitro. Cell proliferation was assessed using Cell Counting Kit-8 assay and Ki-67 staining. Flow cytometry was used to analyze cell surface markers, T-cell proliferation and immune cell infiltration. The collagen-induced arthritis (CIA) mouse model and bleomycin-induced model of lung fibrosis (BLE) were established and treated with hESC-MSCs intravenously for in vivo assessment. Pathological analyses, reverse transcription-quantitative polymerase chain reaction and Western blotting were conducted to evaluate the efficacy of hESC-MSCs treatment. RESULTS: Intravenous transplantation of hESC-MSCs effectively reduced inflammation in CIA mice in this study. Furthermore, hESC-MSC administration enhanced regulatory T cell infiltration and activation. Additional findings suggest that hESC-MSCs may reduce lung fibrosis in BLE mouse models, indicating their potential to mitigate complications associated with RA progression. In vitro experiments revealed a significant inhibition of T-cell activation and proliferation during co-culture with hESC-MSCs. In addition, hESC-MSCs demonstrated enhanced proliferative capacity compared with traditional primary MSCs. CONCLUSIONS: Transplantation of hESC-MSCs represents a promising therapeutic strategy for RA, potentially regulating T-cell proliferation and differentiation.

The role of PI3K/Akt signaling pathway in chronic kidney disease.

Chronic kidney disease (CKD), including chronic glomerulonephritis, IgA nephropathy and diabetic nephropathy, are common chronic diseases characterized by structural damage and functional decline of the kidneys. The current treatment of CKD is symptom relief. Several studies have reported that the phosphatidylinositol 3 kinases (PI3K)/protein kinase B (Akt) signaling pathway is a pathway closely related to the pathological process of CKD. It can ameliorate kidney damage by inhibiting this signal pathway which is involved with inflammation, oxidative stress, cell apoptosis, epithelial mesenchymal transformation (EMT) and autophagy. This review highlights the role of activating or inhibiting the PI3K/Akt signaling pathway in CKD-induced inflammatory response, apoptosis, autophagy and EMT. We also summarize the latest evidence on treating CKD by targeting the PI3K/Akt pathway, discuss the shortcomings and deficiencies of PI3K/Akt research in the field of CKD, and identify potential challenges in developing these clinical therapeutic CKD strategies, and provide appropriate solutions.

Extracorporeal photopheresis reduces inflammation and joint damage in a rheumatoid arthritis murine model.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammatory reactions and tissue damage in the joints. Long-term drug use in clinical practice is often accompanied by adverse reactions. Extracorporeal photopheresis (ECP) is an immunomodulatory therapy with few side effects, offering a potential and safe therapeutic alternative for RA through the induction of immune tolerance. This study aimed to investigate the therapeutic effects of ECP on RA using a collagen-induced arthritis (CIA) murine model, as well as to explore its immunomodulatory effects in vivo. Additionally, particular attention was given to the significant role of monocytes during the ECP process. METHODS: A murine model of rheumatoid arthritis was established by administering two injections of bovine type II collagen to DBA/1J mice. ECP, ECP-MD (mononuclear cells were depleted during the ECP), MTX, and PBS treatment were applied to the CIA mice. During the treatment process, clinical scores and body weight changes of CIA mice were closely monitored. After six treatment sessions, micro-CT images of the hind paws from live mice were captured. Ankle joints and paws of the mice were collected and processed for histological evaluation. Spleen samples were collected to measure the Th17/Treg cells ratio, and serum samples were collected to assess cytokine and anti-type II collagen IgG levels. Monocytes and dendritic cells populations before and after ECP in vitro were detected by flow cytometry. RESULT: ECP therapy significantly attenuated the progression of CIA, alleviated the severity of clinical symptoms in CIA mice and effectively suppressed synovial hyperplasia, inflammation, and cartilage damage. There was an expansion in the percentage of CD3 + CD4 + CD25 + FoxP3 + Tregs and a decrease in CD3 + CD4 + IL17A + Th17 cells in vivo. Furthermore, ECP reduced the serum levels of pro-inflammatory cytokines IL-6 (53.47 ± 7.074 pg/mL vs 5.142 ± 1.779 pg/mL, P < 0.05) and IL-17A (3.077 ± 0.401 pg/mL vs 0.238 ± 0.082 pg/mlL, P < 0.0001) compared with PBS. Interestingly, the depletion of monocytes during the ECP process did not lead to any improvement in clinical symptoms or histological scores in CIA mice. Moreover, the imbalance in the Th17/Treg cells ratio became even more pronounced, accompanied by an augmented secretion of pro-inflammatory cytokines IL-6 and IL-17A. In vitro, compared with cells without ECP treatment, the proportion of CD11b + cells were significantly reduced (P < 0.01), the proportion of CD11c + cells were significantly elevated (P < 0.001) 24 h after ECP treatment. Additionally, the expression of MHC II (P < 0.0001), CD80 (P < 0.01), and CD86 (P < 0.001) was downregulated in CD11c + cells 24 h after ECP treatment. CONCLUSION: Our study demonstrates that ECP exhibits a therapeutic effect comparable to conventional therapy in CIA mice, and the protective mechanisms of ECP against RA involve Th17/Treg cells ratio, which result in decreased IL-6 and IL-17A. Notably, monocytes derived from CIA mice are an indispensable part to the efficacy of ECP treatment, and the proportion of monocytes decreased and the proportion of tolerogenic dendritic cells increased after ECP treatment in vitro.

The Effect of Uncertainty Training on the Improvement of Diagnostic Ability in Chinese Medical Students.

Objective: To evaluate the effect of the uncertainty training on improvement of students' diagnostic ability. Methods: Data were collected on 70 fifth-year medical students enrolled in the Case Discussion courses on Obstetrics and Gynecology in the spring of 2020. Of these students, 36 were in the uncertainty training group and 34 in the control group. The effect of training was evaluated by cognitively diagnostic assessment which mapped exam questions to 4 attributes assessing clinical reasoning and basic science knowledge. Results: Uncertainty training was able to improve students' ability to use basic science concepts for inference and problem solving, and the ability to integrate complex clinical information to arrive at a diagnosis. But it could not improve students' ability on the basic recall of foundational concepts and the ability to use basic science concepts in clinical reasoning. Medical students could do well in integrating complex clinical information although they didn't recall basic science knowledge well. Conclusion: Uncertainty training could be used as an effective teaching method in Case Discussion course on Obstetrics and Gynecology. However, students still need to improve their basic knowledge besides the training.

Sulfur-bridge ligands altering the microenvironment of single-atom CoN3S sites to boost the oxygen reduction reaction.

We report here an asymmetric N,S-coordinated cobalt-based single-atom catalyst with sulfur (S)-bridge ligands (Co-N/S-C) for the oxygen reduction reaction (ORR). The Co-N/S-C exhibits a half-wave potential (E1/2) of 0.908 V versus RHE, outperforming most state-of-the-art ORR catalysts. Theoretical calculations indicate that the CoN3SC10-S moiety facilitates the ORR kinetics by optimizing the adsorption of intermediates. This work provides new insights into the design of single-atom catalysts for electrocatalysis through heteroatom-bridge ligand engineering.

Correlation of Gut Microbiota with Children Obesity and Weight Loss.

Children obesity is a serious public health problem drawing much attention around the world. Recent research indicated that gut microbiota plays a vital role in children obesity, and disturbed gut microbiota is a prominent characteristic of obese children. Diet and exercise are efficient intervention for weight loss in obesity children, however, how the gut microbiota is modulated which remains largely unknown. To characterize the feature of gut microbiota in obese children and explore the effect of dietary and exercise on gut microbiota in simple obese children, 107 healthy children and 86 obese children were recruited, and among of the obese children 39 received the dietary-exercise combined weight loss intervention (DEI). The gut microbiota composition was detected by the 16S amplicon sequencing method. The gut microbiota composition was significantly different between obese children and the healthy cohort, and DEI significantly reduced the body weight and ameliorated the gut microbiota dysbiosis. After DEI, the abundance of the Akkermansia muciniphila was increased, while the abundance of the Sutterella genus was decreased in simple obese children. Our results may provide theoretical reference for future personalized obesity interventions based on gut microbiota. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01088-3.

Salivary proteins potentially derived from horizontal gene transfer are critical for salivary sheath formation and other feeding processes.

Herbivorous insects employ an array of salivary proteins to aid feeding. However, the mechanisms behind the recruitment and evolution of these genes to mediate plant-insect interactions remain poorly understood. Here, we report a potential horizontal gene transfer (HGT) event from bacteria to an ancestral bug of Eutrichophora. The acquired genes subsequently underwent duplications and evolved through co-option. We annotated them as horizontal-transferred, Eutrichophora-specific salivary protein (HESPs) according to their origin and function. In Riptortus pedestris (Coreoidea), all nine HESPs are secreted into plants during feeding. The RpHESP4 to RpHESP8 are recently duplicated and found to be indispensable for salivary sheath formation. Silencing of RpHESP4-8 increases the difficulty of R. pedestris in probing the soybean, and the treated insects display a decreased survivability. Although silencing the other RpHESPs does not affect the salivary sheath formation, negative effects are also observed. In Pyrrhocoris apterus (Pyrrhocoroidea), five out of six PaHESPs are secretory salivary proteins, with PaHESP3 being critical for insect survival. The PaHESP5, while important for insects, no longer functions as a salivary protein. Our results provide insight into the potential origin of insect saliva and shed light on the evolution of salivary proteins.

Cellular senescence imaging and senolysis monitoring in cancer therapy based on a ß-galactosidase-activated aggregation-induced emission luminogen.

Cellular senescence is a permanent state of cell cycle arrest characterized by increased activity of senescence associated ß-galactosidase (SA-ß-gal). Notably, cancer cells have been also observed to exhibit the senescence response and are being considered for sequential treatment with pro-senescence therapy followed by senolytic therapy. However, there is currently no effective agent targeting ß-galactosidase (ß-Gal) for imaging cellular senescence and monitoring senolysis in cancer therapy. Aggregation-induced emission luminogen (AIEgen) demonstrates strong fluorescence, good photostability, and biocompatibility, making it a potential candidate for imaging cellular senescence and monitoring senolysis in cancer therapy when endowed with ß-Gal-responsive capabilities. In this study, we introduced a ß-Gal-activated AIEgen named QM-ß-gal for cellular senescence imaging and senolysis monitoring in cancer therapy. QM-ß-gal exhibited good amphiphilic properties and formed aggregates that emitted a fluorescence signal upon ß-Gal activation. It showed high specificity towards the activity of ß-Gal in lysosomes and successfully visualized DOX-induced senescent cancer cells with intense fluorescence both in vitro and in vivo. Encouragingly, QM-ß-gal could image senescent cancer cells in vivo for over 14 days with excellent biocompatibility. Moreover, it allowed for the monitoring of senescent cancer cell clearance during senolytic therapy with ABT263. This investigation indicated the potential of the ß-Gal-activated AIEgen, QM-ß-gal, as an in vivo approach for imaging cellular senescence and monitoring senolysis in cancer therapy via highly specific and long-term fluorescence imaging. STATEMENT OF SIGNIFICANCE: This work reported a ß-galactosidase-activated AIEgen called QM-ß-gal, which effectively imaged DOX-induced senescent cancer cells both in vitro and in vivo. QM-ß-gal specifically targeted the increased expression and activity of ß-galactosidase in senescent cancer cells, localized within lysosomes. It was cleared rapidly before activation but maintained stability after activation in the DOX-induced senescent tumor. The AIEgen exhibited a remarkable long-term imaging capability for senescent cancer cells, lasting over 14 days and enabled monitoring of senescent cancer cell clearance through ABT263-induced apoptosis. This approach held promise for researchers seeking to achieve prolonged imaging of senescent cells in vivo.

The application of two drainage angles in neurocritical care patients with complicated pneumonia: a randomized controlled trial.

Background: Although head elevation is an early first-line treatment for elevated intracranial pressure (ICP), the use of the head-down or prone position in managing neurocritical patients is controversial because a change in a position directly affects the intracranial and cerebral perfusion pressure, which may cause secondary brain injury and affect patient outcomes. This study compared the effects of two postural drainage positions (30° head-up tilt and 0° head flat) on the prognosis of neurocritical care patients with complicated pneumonia and a clinical pulmonary infection score (CPIS) ≥5 points to provide a reference for selecting appropriate postural drainage positions for patients with pneumonia in neurocritical care units. Methods: A prospective randomized controlled study was conducted with 62 neurocritical care patients with complicated pneumonia. The patients were categorized into control (=31) and experimental (=31) groups in a 1:1 ratio using a simple randomized non-homologous pairing method. Emphasis was placed on matching the baseline characteristics of the two groups, including patient age, sex, height, weight, Glasgow Coma Scale score, heart rate, mean arterial pressure, cough reflex, and mechanical ventilation usage to ensure comparability. Both groups received bundled care for artificial airway management. The control group maintained a standard postural drainage position of 0° head-flat, whereas the experimental group maintained a 30° head-up tilt. The efficacy of the nursing intervention was evaluated by comparing the CPIS and other therapeutic indicators between the two groups after postural drainage. Results: After the intervention, the within-group comparison showed a significant decrease in the CPIS (P < 0.001); procalcitonin levels showed a significant decreasing trend (P < 0.05); the arterial oxygen pressure significantly increased (P < 0.05); the oxygenation index significantly increased (P < 0.001); and the aspiration risk score showed a significant decreasing trend (P < 0.001). A between-group comparison showed no significant differences in any of the indicators before and after the intervention (P < 0.05). Conclusion: Postural drainage positions of 30° head-up tilt and 0° head-flat can improve the CPIS and oxygenation in patients without adverse effects. Therefore, we recommend that patients under neurological intensive care and having pneumonia be drained in a 30° head-up tilt position with good centralized care of the lung infection. Trial registration: The study, "Study of Angles of Postural Drainage in Neurocritical Patients with Pneumonia," was registered in the Protocol Registration Data Element Definitions for Interventional Study database (# ChiCTR2100042155); date of registration: 2021-01-14.

Positron Emission Tomography Imaging of Synaptic Dysfunction in Parkinson's Disease.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases with a complex pathogenesis. Aggregations formed by abnormal deposition of alpha-synuclein (αSyn) lead to synapse dysfunction of the dopamine and non-dopamine systems. The loss of dopaminergic neurons and concomitant alterations in non-dopaminergic function in PD constitute its primary pathological manifestation. Positron emission tomography (PET), as a representative molecular imaging technique, enables the non-invasive visualization, characterization, and quantification of biological processes at cellular and molecular levels. Imaging synaptic function with PET would provide insights into the mechanisms underlying PD and facilitate the optimization of clinical management. In this review, we focus on the synaptic dysfunction associated with the αSyn pathology of PD, summarize various related targets and radiopharmaceuticals, and discuss applications and perspectives of PET imaging of synaptic dysfunction in PD.