Trastuzumab-functionalized bionic pyrotinib liposomes for targeted therapy of HER2-positive breast cancer.

In this study, we prepared a bionic nanosystem of trastuzumab-functionalized SK-BR-3 cell membrane hybrid liposome-coated pyrotinib (Ptb-M-Lip-Her) for the treatment of HER2-positive breast cancer. Transmission electron microscopy, dynamic light scattering, polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting were used to verify the successful preparation of Ptb-M-Lip-Her. In vitro drug release experiments proved that Ptb-M-Lip-Her had a sustained release effect. Cell uptake experiments and in vivo imaging experiments proved that Ptb-M-Lip-Her had good targeting ability to homologous tumor cells (SK-BR-3). The results of cell experiments such as MTT, flow cytometry, immunofluorescence staining and in vivo antitumor experiments showed that Ptb-M-Lip-Her could significantly promote apoptosis and inhibit the proliferation of SK-BR-3 cells. These results clearly indicated that Ptb-M-Lip-Her may be a promising biomimetic nanosystem for targeted therapy of HER2-positive breast cancer.

Natural variation of WBR7 confers rice high yield and quality by modulating sucrose supply in sink organs.

Grain chalkiness is an undesirable trait that negatively regulates grain yield and quality in rice. However, the regulatory mechanism underlying chalkiness is complex and remains unclear. We identified a positive regulator of white-belly rate (WBR). The WBR7 gene encodes sucrose synthase 3 (SUS3). A weak functional allele of WBR7 is beneficial in increasing grain yield and quality. During the domestication of indica rice, a functional G/A variation in the coding region of WBR7 resulted in an E541K amino acid substitution in the GT-4 glycosyltransferase domain, leading to a significant decrease in decomposition activity of WBR7A (allele in cultivar Jin23B) compared with WBR7G (allele in cultivar Beilu130). The NIL(J23B) and knockout line NIL(BL130)KO exhibited lower WBR7 decomposition activity than that of NIL(BL130) and NIL(J23B)COM, resulting in less sucrose decomposition and metabolism in the conducting organs. This caused more sucrose transportation to the endosperm, enhancing the synthesis of storage components in the endosperm and leading to decreased WBR. More sucrose was also transported to the anthers, providing sufficient substrate and energy supply for pollen maturation and germination, ultimately leading to an increase rate of seed setting and increased grain yield. Our findings elucidate a mechanism for enhancing rice yield and quality by modulating sucrose metabolism and allocation, and provides a valuable allele for improved rice quality.

QTL Analysis for Rice Quality-Related Traits and Fine Mapping of qWCR3.

The quality of rice, evaluated using multiple quality-related traits, is the main determinant of its market competitiveness. In this study, two japonica rice varieties with significant differences in quality-related traits were used as parents to construct two populations, BC3F2 and BC3F2:3, with Kongyu131 (KY131) as the recurrent parent. A genetic linkage map was constructed using the BC3F2 population based on 151 pairs of SSR/InDel polymorphic markers selected between the parents. Grain-shape-related traits (grain length GL, grain width GW, and length-to-width ratio LWR), chalkiness-related traits (white-core rate WCR, white-belly rate WBR, white-back rate BR, and chalkiness rate CR), and amylose content (AC) were investigated in the two populations in 2017 and 2018. Except for BR and CR, the traits showed similar characteristics with a normal distribution in both populations. Genetic linkage analysis was conducted for these quality-related traits, and a total of 37 QTLs were detected in the two populations. Further validation was performed on the newly identified QTLs with larger effects, and three grain shape QTLs and four chalkiness QTLs were successfully validated in different environments. One repeatedly validated QTL, qWCR3, was selected for fine mapping and was successfully narrowed down to a 100 kb region in which only two genes, LOC_0s03g45210 and LOC_0s03g45320, exhibited sequence variations between the parents. Furthermore, the variation of LOC_Os03g45210 leads to a frameshift mutation and premature protein termination. The results of this study provide a theoretical basis for positional cloning of the qWCR3 gene, thus offering new genetic resources for rice quality improvement.

[Interaction between central nervous system and immune system after ischemic stroke and its therapeutic significance of traditional Chinese medicine].

Ischemic stroke is divided into acute phase, subacute phase, and recovery phase, with different pathological and physiological characteristics manifested at each stage. Among them, immune and inflammatory reactions persist for several days and weeks after ischemia. Ischemic stroke not only triggers local inflammation in damaged brain regions but also induces a disorder in the immune system, thereby promoting neuroinflammation and exacerbating brain damage. Therefore, conducting an in-depth analysis of the interaction between the central nervous system and the immune system after ischemic stroke, intervening in the main factors of the interaction between them, blocking pathological cascades, and thereby reducing brain inflammation have become the treatment strategies for ischemic stroke. This study summarizes and sorts out the interaction pathways between the central nervous system and the immune system. The impact of the central nervous system on the immune system can be analyzed from the perspective of the autonomic nervous system, the hypothalamic-pituitary-adrenal axis(HPA), and local inflammatory stimulation. The impact of the immune system on the central nervous system can be analyzed from the dynamic changes of immune cells. At the same time, the relevant progress in the prevention and treatment of traditional Chinese medicine(TCM) is summarized, so as to provide new insights for the analysis of complex mechanisms of TCM in preventing and treating ischemic stroke.

Genome-wide identification, characterization and transcriptional profile of the SWEET gene family in Dendrobium officinale.

BACKGROUND: Dendrobium officinale Kimura et Migo (D. officinale) is a well-known traditional Chinese medicine with high content polysaccharides in stems. The SWEET (Sugars Will Eventually be Exported Transporters) family is a novel class of sugar transporters mediating sugar translocation among adjacent cells of plants. The expression patterns of SWEETs and whether they are associated with stress response in D. officinale remains uncovered. RESULTS: Here, 25 SWEET genes were screened out from D. officinale genome, most of which typically contained seven transmembrane domains (TMs) and harbored two conserved MtN3/saliva domains. Using multi-omics data and bioinformatic approaches, the evolutionary relationship, conserved motifs, chromosomal location, expression patterns, correlationship and interaction network were further analyzed. DoSWEETs were intensively located in nine chromosomes. Phylogenetic analysis revealed that DoSWEETs were divided into four clades, and conserved motif 3 specifically existed in DoSWEETs from clade II. Different tissue-specific expression patterns of DoSWEETs suggested the division of their roles in sugar transport. In particular, DoSWEET5b, 5c, and 7d displayed relatively high expression levels in stems. DoSWEET2b and 16 were significantly regulated under cold, drought, and MeJA treatment, which were further verified using RT-qPCR. Correlation analysis and interaction network prediction discovered the internal relationship of DoSWEET family. CONCLUSIONS: Taken together, the identification and analysis of the 25 DoSWEETs in this study provide basic information for further functional verification in D. officinale.

COVID-19 mRNA vaccine immunogenicity decay and breakthrough illness in adolescents and young adults with childhood-onset rheumatic diseases.

OBJECTIVES: To evaluate the humoral immunogenicity for 6 months after the two-dose coronavirus disease 2019 (COVID-19) mRNA vaccination in adolescents and young adults (AYAs) with childhood-onset rheumatic diseases (cRDs). METHODS: This monocentric observational study was conducted between August 2020 and March 2022. Humoral immunogenicity was assessed at 2-3 weeks after first vaccine dose and 1, 3 and 6 months after the second dose by the cPass™ severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralization antibody (nAb) assay. An inhibition signal of ≥30% defined the seroconversion threshold and the readings were calibrated against the World Health Organization International Standard for SARS-CoV-2 antibodies. RESULTS. ONE HUNDRED AND SIXTY-NINE: AYAs with cRDs were recruited [median age 16.8 years (interquartile range, IQR 14.7-19.5), 52% female, 72% Chinese]. JIA (58%) and SLE (18%) comprised the major diagnoses. After second vaccine dose, 99% seroconverted with a median nAb titre of 1779.8 IU/ml (IQR 882.8-2541.9), declining to 935.6 IU/ml (IQR 261.0-1514.9) and 683.2 IU/ml (IQR 163.5-1400.5) at the 3- and 6-month timepoints, respectively. The diagnosis of JIA [odds ratio (OR) 10.1, 95% CI 1.8-58.4, P = 0.010] and treatment with anti-TNF-α (aTNF) (OR 10.1, 95% CI 1.5-70.0, P = 0.019) were independently associated with a >50% drop of nAb titres at 6 months. Withholding MTX or MMF did not affect the vaccine response or decay rate. The COVID-19 breakthrough infection was estimated at 18.2 cases/1000 patient-months with no clinical risk factors identified. CONCLUSION: Over half of AYAs with cRDs had a significant drop in SARS-CoV-2 nAb at 6-month despite an initial robust humoral response. JIA and aTNF usage are predictors of a faster decay rate.

Regioselective Dehydrogenative Reverse Prenylation of Indoles with 2-Methyl-2-butene.

Bulk chemical 2-methyl-2-butene, one of the main C5 distillates of the petrochemical industry, has scarcely been utilized directly in synthesizing high-value-added fine chemicals. Herein, we use 2-methyl-2-butene as the starting material to develop a palladium-catalyzed highly site- and regio-selective C-3 dehydrogenation reverse prenylation of indoles. This synthetic method features mild reaction conditions, a broad substrate scope, atom- and step-economies.

Nutrients and bioactives in citrus fruits: Different citrus varieties, fruit parts, and growth stages.

Citrus fruits are consumed in large quantities worldwide due to their attractive aromas and taste, as well as their high nutritional values and various health-promoting effects, which are due to their abundance of nutrients and bioactives. In addition to water, carbohydrates, vitamins, minerals, and dietary fibers are important nutrients in citrus, providing them with high nutritional values. Citrus fruits are also rich in various bioactives such as flavonoids, essential oils, carotenoids, limonoids, and synephrines, which protect from various ailments, including cancer and inflammatory, digestive, and cardiovascular diseases. The composition and content of nutrients and bioactives differ significantly among citrus varieties, fruit parts, and growth stages. To better understand the nutrient and bioactive profiles of citrus fruits and provide guidance for the utilization of high-value citrus resources, this review systematically summarizes the nutrients and bioactives in citrus fruit, including their contents, structural characteristics, and potential health benefits. We also explore the composition variation in different citrus varieties, fruits parts, and growth stages, as well as their health-promoting effects and applications.

Favorable Propylene-Incorporated Terpolymerization of Ethylene with CO Mediated by Cationic [P,O]-Pd and Ni Complexes.

Commercial polyketone materials are generally produced by palladium-catalyzed terpolymerization of ethylene and α-olefin with carbon monoxide (CO), and rare examples were reported regarding the incorporation of propylene into an ethylene/CO copolymer chain using a cost-effective nickel catalyst. In this study, we have developed a series of [P,O]-type cationic Pd and Ni complexes supported by a diphosphazane monoxide (PNPO) platform, and the electronic and steric effect on phosphine, amine, and phosphine oxide moieties is systematically investigated for terpolymerization in terms of activity, propylene/CO (C3) incorporation, and molecular weight control. It is observed that the melting temperature (Tm) is proportional to the number of C3 incorporations present in the polymer chain, and the incorporated propylene does not affect the degradation temperature substantially, thus broadening the processing temperature window of the resultant polyketones. Notably, in comparison with dppp-type catalysts, PNPO catalysts exhibited a higher preference for propylene consumption, which is of great importance for making more efficient use of α-olefin resources.

Paraventricular thalamus controls consciousness transitions during propofol anaesthesia in mice.

BACKGROUND: The neuronal mechanisms underlying propofol-induced modulation of consciousness are poorly understood. Neuroimaging studies suggest a potential role for non-specific thalamic nuclei in propofol-induced loss of consciousness. We investigated the contribution of the paraventricular thalamus (PVT), a midline thalamic nucleus that has been implicated in arousal control and general anaesthesia with inhaled anaesthetics, to loss and recovery of consciousness during propofol anaesthesia. METHODS: Polysomnographic recordings and righting reflex test were used to determine the transitions of loss and recovery of righting reflex, used as a measure of consciousness in mice, during propofol anaesthesia in mice under conditions mimicking clinical propofol administration. PVT neuronal activities were monitored using fibre photometry and regulated using optogenetic and chemogenetic methods. RESULTS: Population activities of PVT glutamatergic neurones began to decrease before propofol-induced loss of consciousness and rapidly increased to a peak at the onset of recovery of consciousness. Chemogenetic inhibition of PVT calretinin-expressing (PVTCR) neurones shortened onset (from 176 [35] to 127 [26] s; P=0.001) and prolonged return (from 1568 [611] to 3126 [1616] s; P=0.002) of righting reflex. Conversely, chemogenetic activation of PVTCR neurones exerted opposite effects. Furthermore, optogenetic silencing of PVTCR neurones accelerated transitions to loss of consciousness (from 205 [35] to 158 [44] s; P=0.027) and slowed transitions to recovery of consciousness (from 230 [78] to 370 [99] s; P=0.041). During a steady period of unconsciousness maintained with continuous propofol infusion, brief optical activation of PVTCR neurones restored cortical activity and arousal with a latency of about 5 s. CONCLUSIONS: The paraventricular thalamus contributes to the control of consciousness transitions in propofol anaesthesia in mice. This provides a potential neuroanatomical target for controlling consciousness to reduce anaesthetic dose requirements and side effects.

Sialendoscopy-assisted combined approach for parotid sialolithotomy: Our long-term experience.

OBJECTIVES: To assess the long-term outcome of sialendoscopy-assisted combined approach for parotid sialolithotomy with gland preservation. PATIENTS AND METHODS: A retrospective study of patients treated with a combined sialendoscopic and open approach was conducted between 2011 and 2020. Demographic data of patients such as operative technique, stone size, stone location, complications, and symptom relief were collected. Patients were followed up via clinical examination and questionnaires. RESULTS: Seventy-four patients were included and underwent endoscopy-assisted combined operations for the removal of 98 parotid stones. Of the 98 stones, 92(94%) stones were completely removed and 6(6%) were partially removed. At a mean follow-up of 47.1 ± 35 months, 65 of 74 patients (88%) achieved long-term success. Patients with stone incomplete removal were significantly more often to develop the recurrence of obstructive symptoms (p = 0.000) There were no cases of facial nerve injury or fistula formation. Gland function was preserved in 73 of 74 patients (99%). CONCLUSIONS: The combined approach for parotid stones is a safe and gland-preserving alternative to parotidectomy. The techniques described here show high success rates and good long-term results, and they avoided the need for gland resection in >95% of cases.

The predictive value of laboratory tests in oro-maxillofacial infection of different severity.

OBJECTIVE: We aimed to investigate the value of individual laboratory tests and combinations of tests for predicting disease severity. METHODS: We retrospectively reviewed 62 patients with space infections in the oral and maxillofacial head and neck regions. Patients were divided into three groups according to severity. Laboratory tests associated with disease severity were identified. RESULTS: As the severity of infection increased, leukocytes, neutrophils, C-reactive protein (CRP), procalcitonin (PCT), soluble interleukin receptor (sILR) 2, IL6, and creatinine (CR) increased. In the ROC analysis of group 1 (moderate infection) versus group 2 (severe infection), the area under the curve (AUC) values for leukocytes (AUC = 0.724), neutrophils (AUC = 0.714), PCT (AUC = 0.762) and a combination of the 3 tests (AUC = 0.768) suggested a strong predictive value. Furthermore, in the ROC analysis of group 2 (severe infection) versus group 3 (extremely severe infection), the AUC values for CRP (AUC = 0.84), PCT (AUC = 0.799), sIL2R (AUC = 0.937), IL6 (AUC = 0.863) and a combination of the four tests (AUC = 0.943) suggested a strong predictive value. CONCLUSIONS: Leukocytes, neutrophils, and PCT were associated with multispace infection and high severity. CRP, PCT, sIL2R, and/or IL6 were associated with extremely severe infections occurring in the oral and maxillofacial head and neck regions.

Neighboring Molecular Engineering in Diels-Alder Chemistry Enabling Easily Recyclable Carbon Fiber Reinforced Composites.

Although a variety of dynamic covalent bonds have been successfully used in the development of diverse sustainable thermosetting polymers and their composites, solving the trade-off between recovery efficiency and comprehensive properties is still a major challenge. Herein, a "one-stone-two-birds" strategy of lower rotational energy barrier (Er ) phosphate-derived Diels-Alder (DA) cycloadditions was proposed for easily recyclable carbon fiber (CF)-reinforced epoxy resins (EPs) composites. In such a strategy, the phosphate spacer with lower Er accelerated the segmental mobility and dynamic DA exchange reaction for network rearrangement to achieve high-efficiency repairing, reprocessing of the EPs matrix and its composites and rapid nondestructive recycling of CF; meanwhile, incorporating phosphorus-based units especially reduced their fire hazards. The resulting materials simultaneously showed excellent thermal/mechanical properties, superb fire safety and facile recyclability, realizing the concept of recycling for high-performance thermosetting polymers and composites. This strategy is of great significance for understanding and enriching the molecular connotation of DA chemistry, making it potentially applicable to the design and development of a wide range of dynamic covalent adaptable materials toward practical cutting-edge-tech applications.

Robust neutralizing antibody response to SARS-CoV-2 mRNA vaccination in adolescents and young adults with childhood-onset rheumatic diseases.

OBJECTIVES: Immunogenicity to the SARS-CoV-2 mRNA vaccines in adolescents and young adults (AYA) with childhood-onset rheumatic diseases (cRD) is unknown. We aimed to evaluate the humoral immunogenicity and safety of the vaccines in our AYA with cRD. METHODS: A monocentric observational study with 159 AYA (50.3% female and 70.4% Chinese). Humoral immunogenicity was assessed at 2-3 and 4-6 weeks following first and second vaccination by cPass™ SARS-CoV-2 Neutralization Antibody Assay. Inhibition signal of ≥30% defined the cut-off for positive detection of the SARS-CoV-2 neutralizing antibodies. Vaccine safety and disease activity were assessed within 6 weeks after second vaccination. RESULTS: A total of 64.9% and 99.1% of 159 patients (median age: 16.9, IQR: 14.7-19.5) mounted positive SARS-CoV-2 neutralizing responses after first and second vaccination, respectively. Most patients (89.8%) had ≥90% inhibition signal after second vaccination. Methotrexate and mycophenolate mofetil increased the risk associated with negative cPass neutralization responses following the first vaccination. Holding both medications after each vaccination did not affect immunogenicity. There was no symptomatic COVID-19 infection. Local reaction remained the most common (23.3-25.2%) adverse event, without serious complication. Two and seven patients flared following the first and second vaccination, respectively. Subgroup analyses of the 12-18-year-old cohort did not show any differences in vaccine efficacy, predictors of poor response and general safety, but higher proportion of disease flares. CONCLUSIONS: SARS-CoV-2 mRNA vaccines were efficacious after the two-dose regimen in almost all AYA with cRD without serious adverse event. The rate of disease flare observed is 4.4% after the second mRNA vaccine dose.

Prognostic biomarkers of malignant patients with pleural effusion: a systematic review and meta-analysis.

BACKGROUND: Pleural effusion is a common clinical problem in patients with cancer. We aimed to summarize all the known prognostic indicators of malignant pleural effusion. METHODS: We did a systematic review and meta-analysis with a systematic literature search. All prospective or retrospective cohort studies that estimated the prognostic factors of malignant pleural effusion were enrolled. Mantel-Haenszel method was used to calculate the pooled hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Eventually, we identified 82 studies with a total of 10,748 patients that met our inclusion criteria. The LENT score showed a good prognostic value (HR 1.97, 95% CI 1.67-2.31) so did the LENT score item. In addition, clinical parameters like stage (HR 1.68, 95% CI 1.25-2.25), distant metastasis (HR 1.62, 95% CI 1.38-1.89), EGFR mutation (HR 0.65, 95% CI 0.56-0.74), serum biological parameters like hemoglobin (HR 1.56, 95% CI 1.17-2.06), albumin (HR 1.71, 95% CI 1.25-2.34), C-reaction protein (HR 1.84, 95% CI 1.49-2.29), VEGF (HR 1.70, 95% CI 1.18-2.43) and pleural effusion biological parameters like PH (HR 1.95, 95% CI 1.46-2.60), glucose (HR 1.75, 95% CI 1.18-2.61), VEGF (HR 1.99, 95% CI 1.67-2.37), and survivin (HR 2.90, 95% CI 1.17-7.20) are also prognostic factors for malignant pleural effusion. CONCLUSIONS: For malignant pleural effusion, LENT score and its items are valuable prognostic biomarkers, so do the clinical parameters like stage, distant metastasis, EGFR mutation, the serum biological parameters like hemoglobin, albumin, C-reaction protein, VEGF and the pleural effusion biological parameters like PH, glucose, VEGF and survivin.

Metallic Sodium Anodes for Advanced Sodium Metal Batteries: Progress, Challenges and Perspective.

Sodium (Na)-based batteries, as the ideal choice of large-scale and low-cost energy storage, have attracted much attention. Na metal anodes with high theoretical specific capacity and low potential are considered to be one of the most promising anodes for next-generation Na-based batteries. However, the high reactivity of Na metal anodes makes the electrode/electrolyte phase unstable, resulting in formation of Na dendrites, short cycle life and safety problems. Herein, the contribution outlines the latest development of Na metal anodes for Na metal batteries. The design strategies for high efficiency utilization of Na metal anodes are elucidated, including sophisticated electrode construction, liquid electrolyte optimization, electrode/electrolyte interface stabilization, and solid electrolyte adaptation. Finally, the future research direction and existing problems are proposed.

TSAd Plays a Major Role in Myo9b-Mediated Suppression of Malignant Pleural Effusion by Regulating TH1/TH17 Cell Response.

Emerging evidence indicates that Myo9b is a cancer metastasis-related protein and functions in a variety of immune-related diseases. However, it is not clear whether and how Myo9b functions in malignant pleural effusion (MPE). In this study, our data showed that Myo9b expression levels correlated with lung cancer pleural metastasis, and nucleated cells in MPE from either patients or mice expressed a lower level of Myo9b than those in the corresponding blood. Myo9b deficiency in cancer cells suppressed MPE development via inhibition of migration. Myo9b deficiency in mice suppressed MPE development by decreasing TH1 cells and increasing TH17 cells. CD4+ naive T cells isolated from Myo9b-/- mouse spleens exhibited less TH1 cell differentiation and more TH17 cell differentiation in vitro. mRNA sequencing of nucleated cells showed that T cell-specific adaptor protein (TSAd) was downregulated in Myo9b-/- mouse MPE, and enrichment of the H3K27me3 mark in the TSAd promoter region was found in the Myo9b-/- group. Naive T cells purified from wild type mouse spleens transfected with TSAd-specific small interfering RNAs (siRNAs) also showed less TH1 cell differentiation and more TH17 cell differentiation than those from the siRNA control group. Furthermore, downregulation of TSAd in mice using cholesterol-conjugated TSAd-specific siRNA suppressed MPE development, decreased TH1 cells, and increased TH17 cells in MPE in vivo. Taken together, Myo9b deficiency suppresses MPE development not only by suppressing pleural cancer metastasis but also by regulating TH1/TH17 cell response via a TSAd-dependent pathway. This work suggests Myo9b and TSAd as novel candidates for future basic and clinical investigations of cancer.

Fine mapping of qTGW2b and qGL9, two minor QTL conferring grain size and weight in rice.

Rice grain size is a key determinant of both grain yield and quality. In this study, we conducted QTL mapping on grain size using a recombinant inbred line (RIL) population derived from a cross between japonica variety Beilu130 (BL130) and indica variety Jin23B (J23B). A total of twenty-two QTL related to grain length (GL), grain width (GW), grain length-to-width ratio (LWR), grain thickness (GT), and thousand grain weight (TGW) were detected under two environments, and 14 of them were repeatedly detected. Two minor QTL, qTGW2b and qGL9, were validated and further delimited to regions of 631 kb and 272 kb, respectively. Parental sequence comparison of genes expressed in inflorescence in corresponding candidate regions identified frameshifts in the exons of LOC_Os02g38690 and LOC_Os02g38780, both of which encode protein phosphatase 2C-containing protein, and LOC_Os09g29930, which encodes a BIM2 protein. Scanning electron microscopy (SEM) analysis revealed that the increase of cell size rather than cell number caused the differences in grain size between NILs of qTGW2b and qGL9. Quantitative RT-PCR analysis showed that the expression levels of EXPA4, EXPA5, EXPA6, EXPB3, EXPB4, and EXPB7 were significantly different in both qTGW2b NILs and qGL9 NILs. Our results lay the foundation for the cloning of qTGW2b and qGL9, and provide genetic materials for the improvement of rice yield and quality. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01328-2.

BST-2/Tetherin is involved in BAFF-enhanced proliferation and survival via canonical NF-κB signaling in neoplastic B-lymphoid cells.

The development of Sjögren's syndrome (SS) is accompanied by B cell hyperproliferation and mutation. Our previous study identified aberrant expression of BST-2 (also known as Tetherin/CD317) in B cells from either the peripheral blood or infiltrated salivary glands. However, the roles of BST-2 in the regulation of B cell activation remain unknown. In this study, we identified that BST-2 can respond to BAFF simulation but not to other B cell simulators in neoplastic B cell lines. A CCK-8 assay, an EdU assay and Annexin V/PI staining indicated that BST-2 inhibition attenuated BAFF-enhanced proliferation and survival in both Raji cells and Daudi cells. Screening of BAFF-related signaling in neoplastic B-lymphoid cells indicated that BST-2 was involved in the regulation of NF-κB signaling upon BAFF simulation. However, inhibition of NF-κB by JSH-23 significantly reduced the proliferation and survival of Raji and Daudi cells under both normal and BAFF-simulated conditions. Collectively, our results indicate that BST-2/Tetherin is a BAFF-responsive membrane factor involved in the regulation of NF-κB signaling, thereby assisting in the proliferation and survival of neoplastic B-lymphoid cells. Our study provides a potential molecular mechanism underlying aberrant overactivation of B cells upon SS development.

Bacteria-driven hypoxia targeting delivery of chemotherapeutic drug proving outcome of breast cancer.

Local hypoxia is a common feature of many solid tumors and may lead to unsatisfactory chemotherapy outcomes. Anaerobic bacteria that have an affinity to hypoxic areas can be used to achieve targeted drug delivery in tumor tissues. In this study, we developed a biocompatible bacteria/nanoparticles biohybrid (Bif@DOX-NPs) platform that employs the anaerobic Bifidobacterium infantis (Bif) to deliver adriamycin-loaded bovine serum albumin nanoparticles (DOX-NPs) into breast tumors. The Bif@DOX-NPs retained the targeting ability of B. infantis to hypoxic regions, as well as the cytotoxicity of DOX. The biohybrids were able to actively colonize the hypoxic tumors and significantly increased drug accumulation at the tumor site. The DOX concentration in the tumor masses colonized by Bif@DOX-NPs was 4 times higher than that in the free DOX-treated tumors, which significantly prolonged the median survival of the tumor-bearing mice to 69 days and reduced the toxic side-effects of DOX. Thus, anaerobic bacteria-based biohybrids are a highly promising tool for the targeted treatment of solid tumors with inaccessible hypoxic regions.