Nosocomial Infections After Pediatric Congenital Heart Disease Surgery: Data from National Center for Cardiovascular Diseases in China.

Purpose: Infection prevention and control (IPC) has a significant impact on the prognosis after pediatric cardiac surgery. This study aimed to provide surveillance data on the incidence and density of various infections during the COVID-19 epidemic and explore the influence of multi-drug resistant organisms (MDRO) on in-hospital prognosis after congenital heart disease surgery. Methods: This single-center retrospective study included pediatric patients who underwent cardiac surgery between 2021 and 2022. The results of the postoperative bacterial and fungal cultures and antimicrobial stewardship were collected. The demographic characteristics (age and weight), operation-related parameters (RACHS-1 grade, duration of cardiopulmonary bypass, and aortic cross clamp), and surgical outcomes (extracorporeal membrane oxygenation, delayed sternal closure, mortality, duration of mechanical ventilation, length of intensive care unit stay and hospital stay, and hospitalization costs) of MDRO and non-MDRO patients were compared. Results: A total of 4776 patients were included. There were 101 infectious culture results after the operation, with a nosocomial infection rate of 2.1%. There were 40 MDRO specimens from 36 patients, 50 non-MDRO specimens from 30 patients, and 11 fungal specimens from 10 patients. The incidence of pneumonia was 1.5%, with a ventilator-associated pneumonia incidence density of 7.2/1000 patient-days. The incidence of sepsis was 0.4%, with a catheter-related bloodstream infection incidence density of 0.24/ 1000 patient-days. The incidence density of catheter-associated tract infection was 0.45/ 1000 patient-days. The incidence of surgical site infection was 0.06%. The culture proportion before commencing antibiotics was 93% and the antibiotic consumption intensity was 30.7 DDD/100 bed-days. The length of intensive care unit stay in MDRO infection patients increased compared with that in non-MDRO infection patients, 30 (18,52) vs 17 (7,62) days, p=0.05). Conclusion: The IPC performance of Fuwai Hospital achieved satisfactory results. MDRO infection can lead to prolonged intensive care unit stay.

Developed countries have advanced infection prevention and control systems and comprehensive postoperative infection monitoring data for congenital heart disease. While developing countries have initiated efforts in infection prevention and control, global attention remains substantial. This study aimed to provide comprehensive infection surveillance data and identify possible implementation for further improvement in the National Center for Cardiovascular Diseases in China (Fuwai Hospital). This was a retrospective single-center study. We included pediatric patients who underwent cardiac surgery at a pediatric surgical center between 2021 and 2022, with an age limit of 14 years. Exclusion criteria included patients undergoing medical therapy, interventional therapy, or surgical therapy in other centers in Fuwai Hospital. This study, for the first time, reports the incidence of comprehensive healthcare-associated infection surveillance and targeted surveillance (encompassing device-associated infection, surgical site infection, and multi-drug resistant organisms) after pediatric cardiac surgery at the National Center for Cardiovascular Diseases in China. In addition, we report the data on antimicrobial stewardship. We compared the surgical outcome and hospitalization costs between patients with multi-drug resistant organism infection and those without multi-drug resistant organism infection and found that multi-drug resistant organism infection can lead to prolonged intensive care unit length of stay. The Fuwai Hospital achieved satisfactory infection prevention and control results. However, because China is a large developing country exhibiting notable variations in medical conditions across its diverse regions, prospective, multicenter, observational studies should be carried out for future research based on existing evidence.

Healthcare-associated infection management in 62 ICUs for patients with congenital heart disease in China: a survey study.

OBJECTIVES: All patients with congenital heart disease (CHD) receive postoperative management in ICUs. Infection prevention and control (IPC) has a significant impact on prognosis. This study provides a preliminary understanding of the fundamental aspects of IPC in ICUs following CHD surgery in China. METHODS: From September to October 2023, we initiated a survey on healthcare-associated infection (HAI) management in hospitals that perform CHD surgeries independently. The questionnaires were jointly completed by the ICU physicians and IPC personnel. Duplicate or unqualified questionnaires were excluded from the study. The contents of our questionnaires covered hospital and ICU capacity, performance of the infection control department, HAI surveillance, implementation of IPC measures, and antimicrobial stewardship (AMS). Qualified questionnaires were compared according to the volume of annual CHD surgeries performed in different ICUs. Group 1 was defined as volume more than 300 cases and group 2 was defined as volume less than or equal to 300 cases. RESULTS: Sixty-two of the 118 questionnaires were completed, with a response rate of 53%. The CHD surgical volume in 2022 of the 62 hospitals was 36342, accounting for 52% of the annual CHD surgical volume (69 672) across the country. The postoperative infection rates obtained from the 15 ICUs varied from 1.3 to 15%, with a median rate of 4.5%. A total of 16 ICUs provided data on drug-resistant bacteria, Klebsiella pneumoniae exhibiting the highest frequency. More than 95% of ICUs have established complete HAI management systems. Information-based HAI surveillance was conducted in 89% of ICUs. Approximately 67% of ICUs stopped prophylactic antibiotics within 48 hours after surgery. In complex cases, carbapenems were administered empirically in 89% of ICUs. Group 1 had an advantage over group 2 in preventing multi-drug-resistant organisms (all instruments should be used alone 100% vs. 86%, P =0.047; cleaning and disinfection of environmental surfaces, 100% vs. 81%, P =0.035; antibiotic consumption control 85% vs. 61%, P =0.044) and in preventing surgical site infections (perioperative blood glucose monitoring, 88% vs. 67%, P =0.048). However, Group 1 did not perform well in preventing catheter-related bloodstream infection (delayed catheter removal due to convenience of laboratory tests, 31% vs. 6%, P =0.021) and catheter-associated urinary tract infection (delayed catheter removal due to muscle relaxant administration, 88% vs. 58%, P =0.022). CONCLUSIONS: A relatively complete HAI management system has been established throughout the country in ICUs for CHD patients. Information-based surveillance of HAI needs to be promoted, and actions should be taken to facilitate the implementation of IPC measures and AMS bundles. Training and feedback are critical for implementing IPC measures.

A comprehensive analysis of immunotherapy in advanced endometrial cancer (Review).

The morbidity and mortality rates of endometrial cancer (EC) are increasing yearly. Early-stage EC can be effectively treated through surgery or surgery combined with radiotherapy and chemotherapy. Advanced and recurrent EC is treated with chemotherapy and comprehensive treatment; however, the prognosis for patients at this disease stage is poor. Consequently, novel and effective treatment strategies are urgently required for these patients. Breakthrough progress has been made with the use of immunosuppressants in the treatment of EC, which have been included in treatment guidelines. In the present review, the etiology and classification of EC was outlined and the relevant scientific basis for the application of immunosuppressants in advanced and recurrent EC was discussed. The relevant published and ongoing clinical trials are also summarized. As such, the present review aimed to provide a scientific summary of immunotherapy of EC.

Enhancing immune responses of ESC-based TAA cancer vaccines with a novel OMV delivery system.

Embryonic stem cell (ESC)-derived epitopes can act as therapeutic tumor vaccines against different types of tumors Jin (Adv Healthc Mater 2023). However, these epitopes have poor immunogenicity and stimulate insufficient CD8+ T cell responses, which motivated us to develop a new method to deliver and enhance their effectiveness. Bacterial outer membrane vesicles (OMVs) can serve as immunoadjuvants and act as a delivery vector for tumor antigens. In the current study, we engineered a new OMV platform for the co-delivery of ESC-derived tumor antigens and immune checkpoint inhibitors (PD-L1 antibody). An engineered Staphylococcal Protein A (SpA) was created to non-specifically bind to anti-PD-L1 antibody. SpyCatcher (SpC) and SpA were fused into the cell outer membrane protein OmpA to capture SpyTag-attached peptides and PD-L1 antibody, respectively. The modified OMV was able to efficiently conjugate with ESC-derived TAAs and PD-L1 antibody (SpC-OMVs + SpT-peptides + anti-PD-L1), increasing the residence time of TAAs in the body. The results showed that the combination therapy of ESC-based TAAs and PD-L1 antibody delivered by OMV had significant inhibitory effects in mouse tumor model. Specifically, it was effective in reducing tumor growth by enhancing IFN-γ-CD8+ T cell responses and increasing the number of CD8+ memory cells and antigen-specific T cells. Overall, the new OMV delivery system is a versatile platform that can enhance the immune responses of ESC-based TAA cancer vaccines.

Nanomaterial-Enabled Photothermal Heating and Its Use for Cancer Therapy via Localized Hyperthermia.

Photothermal therapy (PTT), which employs nanoscale transducers delivered into a tumor to locally generate heat upon irradiation with near-infrared light, shows great potential in killing cancer cells through hyperthermia. The efficacy of such a treatment is determined by a number of factors, including the amount, distribution, and dissipation of the generated heat, as well as the type of cancer cell involved. The amount of heat generated is largely controlled by the number of transducers accumulated inside the tumor, the absorption coefficient and photothermal conversion efficiency of the transducer, and the irradiance of the light. The efficacy of treatment depends on the distribution of the transducers in the tumor and the penetration depth of the light. The vascularity and tissue thermal conduction both affect the dissipation of heat and thereby the distribution of temperature. The successful implementation of PTT in the clinic setting critically depends on techniques for real-time monitoring and management of temperature.

Serum glycoprotein non-metastatic melanoma protein B (GPNMB) level as a potential biomarker for diabetes mellitus-related cataract: A cross-sectional study.

Background: Diabetes mellitus (DM), a metabolic disease that has attracted significant research and clinical attention over the years, can affect the eye structure and induce cataract in patients diagnosed with DM. Recent studies have indicated the relationship between glycoprotein non-metastatic melanoma protein B (GPNMB) and DM and DM-related renal dysfunction. However, the role of circulating GPNMB in DM-associated cataract is still unknown. In this study, we explored the potential of serum GPNMB as a biomarker for DM and DM-associated cataract. Methods: A total of 406 subjects were enrolled, including 60 and 346 subjects with and without DM, respectively. The presence of cataract was evaluated and serum GPNMB levels were measured using a commercial enzyme-linked immunosorbent assay kit. Results: Serum GPNMB levels were higher in diabetic individuals and subjects with cataract than in those without DM or cataract. Subjects in the highest GPNMB tertile group were more likely to have metabolic disorder, cataract, and DM. Analysis performed in subjects with DM elucidated the correlation between serum GPNMB levels and cataract. Receiver operating characteristic (ROC) curve analysis also indicated that GPNMB could be used to diagnose DM and cataract. Multivariable logistic regression analysis illustrated that GPNMB levels were independently associated with DM and cataract. DM was also found to be an independent risk factor for cataract. Further surveys revealed the combination of serum GPNMB levels and presence of DM was associated with a more precise identification of cataract than either factor alone. Conclusions: Increased circulating GPNMB levels are associated with DM and cataract and can be used as a biomarker of DM-associated cataract.

Combined methods elucidate the multi-organ toxicity of cylindrospermopsin (CYN) on Daphnia magna.

Global water bodies are now at risk from inevitable cyanobacterial blooms and their production of multiple cyanotoxins, in particular cylindrospermopsin (CYN). However, research on the CYN toxicity and its molecular mechanisms is still limited, whilst the responses of aquatic species against CYN are uncovered. By integrating behavioral observations, chemical detections and transcriptome analysis, this study demonstrated that CYN exerted multi-organ toxicity to model species, Daphnia magna. The present study confirmed that CYN could cause protein inhibition by undermining total protein contents, and altered the gene expression related to proteolysis. Meantime, CYN induced oxidative stress by increasing reactive oxygen species (ROS) level, decreasing the glutathione (GSH) concentration, and interfered with protoheme formation process molecularly. Neurotoxicity led by CYN was solidly determined by abnormal swimming patterns, reduced acetylcholinesterase (AChE), and downward expression of muscarinic acetylcholine receptor (CHRM). Importantly, for the first time, this research determined CYN directly interfered with energy metabolism in cladocerans. CYN distinctively reduced filtration and ingestion rate by targeting on heart and thoracic limbs, which declined the energy intake, and could be further displayed by the reduction of motional strength and the trypsin concentration. These phenotypic alterations were supported by transcriptomic profile, including the down-regulation of oxidative phosphorylation and ATP synthesis. Moreover, CYN was speculated to trigger the self-defense responses of D. magna, known as "abandon-ship" by moderating lipid metabolism and distribution. This study, overall, comprehensively demonstrated the CYN toxicity and the responses of D. magna against it, which is of great significance to the advancements of CYN toxicity knowledge.

First report of Fusarium proliferatum causing leaf spot on tea plants in Jiangxi Province, China.

Tea (Camellia sinensis (L.) O. Kuntze), a perennial evergreen shrub, is one of the most important cash crops in China. In September 2021, leaf spot symptoms were observed on approximately 30% of tea plants in a 2 ha commercial field of Lushan (29°33'0" N, 115°58'48" E), Jiangxi Province, China. The symptoms initially appeared as small, gray lesions, and later became larger (10-15 mm in diameter) circular to irregular spots with light brown centers and gray borders. To isolate the pathogen, small pieces (3×3 mm) cut from the margins of lesions were sterilized with 75% ethanol for 10 s, 0.1% HgCl2 for 20 s, and then rinsed three times with sterile water. The pieces were placed onto acidified potato dextrose agar (APDA) plates, and incubated in darkness at 28℃. Pure cultures were prepared by subculturing hyphal tips. A total of 16 fungal isolates were obtained, and the colonies of 15 isolates (isolation rate 93.8%) looked identical, resembling those of the genus Fusarium. The colonies were white to pink with purple woolly mycelium. After 10 to 15 days incubation, slightly curved macroconidia with three to four septa measuring 14.0 to 34.5 × 2.0 to 3.5 µm (n = 50), and oval, unicellar microconidia measuring 4.0 to 9.0 × 1.5 to 3.5 µm (n = 50) were observed. These morphological characteristics were similar to that described for Fusarium proliferatum (Leslie and Summerell 2006). Genomic DNA of representative isolates (LSZWY, LSZWY2, LSZWY3) was extracted with the Ezup Column Fungi Genomic DNA Purification Kit (Sangon Biotech Co., Ltd, Shanghai). The translation elongation factor 1 alpha gene (EF-1ɑ) was amplified using primers EF-1H / EF-2T (O'Donnell, et al. 2015). PCR product was sequenced and the sequence was 709 bp (Accession No. OL614004, ON357634, ON595710). BLAST search results showed that it had 99.9% identity with the EF-1ɑ gene sequence of F. proliferatum (MH341215, MT371378). To test pathogenicity, nine leaves from 5-year-old healthy tea plants (Ca. Luyun 3) were wounded using a sterilized needle and inoculated with a 20µl conidial suspension (2 × 107 conidia·mL-1) on one side of the plants and the other side with sterilized distilled water as a control. All leaves were incubated in a growth chamber at 28℃ and 80% relative humidity with a 12 h light/dark photoperiod. Seven days later, all inoculated treatments showed symptoms identical to those observed in the field, while the control remained asymptomatic. The experiment was repeated three times with similar results. Koch's postulates were fulfilled by successful re-isolation and morphological and molecular identification of F. proliferatum from the inoculated leaves. This pathogen can cause diseases of many crops, e.g. tobacco, Polygonatum cyrtonema and others (Li, et al 2017; Zhou, et al. 2021). However, this is the first report of F. proliferatum causing leaf spot on tea plants in China. This new disease poses a threat to the yield and quality of tea and methods need to be developed for its control and to prevent further spread.

Versatile Protein Coronation Approach with Multiple Depleted Serum for Creating Biocompatible, Precision Nanomedicine.

The protein corona effect has long been treated as the evil source behind delivery efficacy issues. In this study, this concept is challenged by showcasing that the protein corona can serve as a versatile functionalization approach to improve the delivery efficacy or mitigate nanocytotoxicity. To this end, the depleted serum is introduced to create nanomaterials carrying functionally distinct protein corona, referred to as PCylated nanomaterials. It is confirmed that the passivation with depleted serum helps reduce the toxicity and pro-inflammatory response. Furthermore, the same method can be leveraged to enhance the capacity of nanomaterials to undergo endocytosis as well as their potential as an agonist for the NF-κB pathways. The comparable stability of protein corona created by late and early-stage serum reveals that the chanceless interaction with nanomaterials, rather than an inadequate binding strength, may be behind the failure of enriching certain components. The PCylation strategy is extended to cancer patient-derived fluid, creating a set of T1 and T3-stage cancer-specific nanotherapeutics to retard the metastasis of cancer cells, while leaving normal endothelial negligibly affected. It is hoped the novel PCylation approach validated here can shed light on the future development of precision nanomedicine with improved delivery efficacy.

St13 protects against disordered acinar cell arachidonic acid pathway in chronic pancreatitis.

BACKGROUND: Early diagnosis and treatment of chronic pancreatitis (CP) are limited. In this study, St13, a co-chaperone protein, was investigated whether it constituted a novel regulatory target in CP. Meanwhile, we evaluated the value of micro-PET/CT in the early diagnosis of CP. METHODS: Data from healthy control individuals and patients with alcoholic CP (ACP) or non-ACP (nACP) were analysed. PRSS1 transgenic mice (PRSS1Tg) were treated with ethanol or caerulein to mimic the development of ACP or nACP, respectively. Pancreatic lipid metabolite profiling was performed in human and PRSS1Tg model mice. The potential functions of St13 were investigated by crossing PRSS1Tg mice with St13-/- mice via immunoprecipitation and lipid metabolomics. Micro-PET/CT was performed to evaluate pancreatic morphology and fibrosis in CP model. RESULTS: The arachidonic acid (AA) pathway ranked the most commonly dysregulated lipid pathway in ACP and nACP in human and mice. Knockout of St13 exacerbated fatty replacement and fibrosis in CP model. Sdf2l1 was identified as a binding partner of St13 as it stabilizes the IRE1α-XBP1s signalling pathway, which regulates COX-2, an important component in AA metabolism. Micro-PET/CT with 68Ga-FAPI-04 was useful for evaluating pancreatic morphology and fibrosis in CP model mice 2 weeks after modelling. CONCLUSION: St13 is functionally activated in acinar cells and protects against the cellular characteristics of CP by binding Sdf2l1, regulating AA pathway. 68Ga-FAPI-04 PET/CT may be a very valuable approach for the early diagnosis of CP. These findings thus provide novel insights into both diagnosis and treatment of CP.

Genome Evolution of Filamentous Cyanobacterium Nostoc Species: From Facultative Symbiosis to Free Living.

In contrast to obligate bacteria, facultative symbiotic bacteria are mainly characterized by genome enlargement. However, the underlying relationship of this feature with adaptations to various habitats remains unclear. In this study, we used the global genome data of Nostoc strains, including 10 novel genomes sequenced in this study and 26 genomes available from public databases, and analyzed their evolutionary history. The evolutionary boundary of the real clade of Nostoc species was identified and was found to be consistent with the results of polyphasic taxonomy. The initial ancestral species of Nostoc was demonstrated to be consistent with a facultative symbiotic population. Further analyses revealed that Nostoc strains tended to shift from facultative symbiosis to a free-living one, along with an increase in genome sizes during the dispersal of each exterior branch. Intracellular symbiosis was proved to be essentially related to Nostoc evolution, and the adaptation of its members to free-living environments was coupled with a large preference for gene acquisition involved in gene repair and recombination. These findings provided unique evidence of genomic mechanisms by which homologous microbes adapt to distinct life manners and external environments.

Roles of kinesin superfamily proteins in colorectal cancer carcinogenesis (Review).

Colorectal cancer (CRC), a commonly occurring carcinoma, now ranks the second in terms of cancer­associated deaths around the world. Among the numerous factors that contribute to CRC tumor progression, a class of motor proteins known as the kinesins has been found to play a vital role. Kinesins are responsible for the intracellular trafficking of functional proteins, organelles and biomacromolecules along microtubules. Dysregulation of kinesins has been revealed to influence the cell cycle to cause abnormal cell growth and affect cell adhesion to promote epithelial­mesenchymal transition in breast, bladder, ovarian and prostate cancer. Studies on the function of kinesins in CRC have also been performed, although, to the best of our knowledge, little is known about the underlying mechanisms of kinesins in CRC progression. The present review outlines the roles played by different kinesins in CRC carcinogenesis, mainly discussing the most studied subfamilies (kinesin 3­6, 8, 10, 11 and 13), This review aims to illustrate the functions of kinesins in CRC cell growth, cancer metastasis and chemoresistance to provide insights regarding kinesins as potential targets for determining CRC prognosis and selecting therapy.

Engineering hiPSC-CM and hiPSC-EC laden 3D nanofibrous splenic hydrogel for improving cardiac function through revascularization and remuscularization in infarcted heart.

Cell therapy has been a promising strategy for cardiac repair after myocardial infarction (MI), but a poor ischemic environment and low cell delivery efficiency remain significant challenges. The spleen serves as a hematopoietic stem cell niche and secretes cardioprotective factors after MI, but it is unclear whether it could be used for human pluripotent stem cell (hiPSC) cultivation and provide a proper microenvironment for cell grafts against the ischemic environment. Herein, we developed a splenic extracellular matrix derived thermoresponsive hydrogel (SpGel). Proteomics analysis indicated that SpGel is enriched with proteins known to modulate the Wnt signaling pathway, cell-substrate adhesion, cardiac muscle contraction and oxidation-reduction processes. In vitro studies demonstrated that hiPSCs could be efficiently induced into endothelial cells (iECs) and cardiomyocytes (iCMs) with enhanced function on SpGel. The cytoprotective effect of SpGel on iECs/iCMs against oxidative stress damage was also proven. Furthermore, in vivo studies revealed that iEC/iCM-laden SpGel improved cardiac function and inhibited cardiac fibrosis of infarcted hearts by improving cell survival, revascularization and remuscularization. In conclusion, we successfully established a novel platform for the efficient generation and delivery of autologous cell grafts, which could be a promising clinical therapeutic strategy for cardiac repair and regeneration after MI.

Deciphering the structure, function, expression and regulation of aquaporin-5 in cancer evolution.

In recent years, the morbidity rate resulting from numerous types of malignant tumor has increased annually, and the treatment of tumors has been attracting an increasing amount of attention. A number of recent studies have revealed that the water channel protein aquaporin-5 (AQP5) has become a major player in multiple types of cancer. AQP5 is abnormally expressed in a variety of tumor tissues or cells and has multiple effects on certain biological functions of tumors, such as regulating the proliferation, apoptosis and migration of tumor cells. It has been suggested that AQP5 may play an important role in the process of tumor development, opening up a new field of tumor research. The present review highlighted the structure of AQP5 and its role in tumor progression. Furthermore, the expression of AQP5 in different malignant neoplasms was summarized. In addition, the influence of not only drugs, but also different compounds on AQP5 were summarized. In conclusion, according to the findings in the present review, AQP5 has potential as a novel therapeutic target in human cancer, and other AQPs should be similarly investigated.

Comparative chloroplast genomes: insights into the evolution of the chloroplast genome of Camellia sinensis and the phylogeny of Camellia.

BACKGROUND: Chloroplast genome resources can provide useful information for the evolution of plant species. Tea plant (Camellia sinensis) is among the most economically valuable member of Camellia. Here, we determined the chloroplast genome of the first natural triploid Chinary type tea ('Wuyi narcissus' cultivar of Camellia sinensis var. sinensis, CWN) and conducted the genome comparison with the diploid Chinary type tea (Camellia sinensis var. sinensis, CSS) and two types of diploid Assamica type teas (Camellia sinensis var. assamica: Chinese Assamica type tea, CSA and Indian Assamica type tea, CIA). Further, the evolutionary mechanism of the chloroplast genome of Camellia sinensis and the relationships of Camellia species based on chloroplast genome were discussed. RESULTS: Comparative analysis showed the evolutionary dynamics of chloroplast genome of Camellia sinensis were the repeats and insertion-deletions (indels), and distribution of the repeats, indels and substitutions were significantly correlated. Chinese tea and Indian tea had significant differences in the structural characteristic and the codon usage of the chloroplast genome. Analysis of sequence characterized amplified region (SCAR) using sequences of the intergenic spacers (trnE/trnT) showed none of 292 different Camellia sinensis cultivars had similar sequence characteristic to triploid CWN, but the other four Camellia species did. Estimations of the divergence time showed that CIA diverged from the common ancestor of two Assamica type teas about 6.2 Mya (CI: 4.4-8.1 Mya). CSS and CSA diverged to each other about 0.8 Mya (CI: 0.4-1.5 Mya). Moreover, phylogenetic clustering was not exactly consistent with the current taxonomy of Camellia. CONCLUSIONS: The repeat-induced and indel-induced mutations were two important dynamics contributed to the diversification of the chloroplast genome in Camellia sinensis, which were not mutually exclusive. Chinese tea and Indian tea might have undergone different selection pressures. Chloroplast transfer occurred during the polyploid evolution in Camellia sinensis. In addition, our results supported the three different domestication origins of Chinary type tea, Chinese Assamica type tea and Indian Assamica type tea. And, the current classification of some Camellia species might need to be further discussed.

Bifunctional Janus Particles as Multivalent Synthetic Nanoparticle Antibodies (SNAbs) for Selective Depletion of Target Cells.

Monoclonal antibodies (mAb) have had a transformative impact on treating cancers and immune disorders. However, their use is limited by high development time and monetary cost, manufacturing complexities, suboptimal pharmacokinetics, and availability of disease-specific targets. To address some of these challenges, we developed an entirely synthetic, multivalent, Janus nanotherapeutic platform, called Synthetic Nanoparticle Antibodies (SNAbs). SNAbs, with phage-display-identified cell-targeting ligands on one "face" and Fc-mimicking ligands on the opposite "face", were synthesized using a custom, multistep, solid-phase chemistry method. SNAbs efficiently targeted and depleted myeloid-derived immune-suppressor cells (MDSCs) from mouse-tumor and rat-trauma models, ex vivo. Systemic injection of MDSC-targeting SNAbs efficiently depleted circulating MDSCs in a mouse triple-negative breast cancer model, enabling enhanced T cell and Natural Killer cell infiltration into tumors. Our results demonstrate that SNAbs are a versatile and effective functional alternative to mAbs, with advantages of a plug-and-play, cell-free manufacturing process, and high-throughput screening (HTS)-enabled library of potential targeting ligands.

α-MSH-PE38KDEL Kills Melanoma Cells via Modulating Erk1/2/MITF/TYR Signaling in an MC1R-Dependent Manner.

BACKGROUND/OBJECTIVE: The immunotoxin α-MSH-PE38KDEL consisting of α-MSH and PE38KDEL showed high cytotoxicity on MSH receptor-positive melanoma cells, suggesting that α-MSH-PE38KDEL might be a potent drug for the treatment of melanoma. Herein, we explored whether the Erk1/2/MITF/TYR signaling, a verified target of α-MSH/MC1R, was involved in α-MSH-PE38KDEL-mediated cytotoxicity. METHODS: Human melanoma cell line A375, mouse melanoma cell line B16-F10, human breast cancer cell line MDA-MB-231 and human primary epidermal melanocytes (HEMa) with different expression levels of MC1R were used in this study. Cell apoptosis and viability were determined by using flow cytometry and MTT assays. Protein expressions were tested by Western blotting. RESULTS: The expression levels of MC1R in A375 and B16-F10 cells were significantly higher than that of MDA-MB-231 and HEMa. α-MSH-PE38KDEL treatment induced a significant inhibition in cell viability in A375 and B16-F10 cells, while showed no obvious influence in the viability of MDA-MB-231 and HEMa cells. However, knockdown of MC1R abolished α-MSH-PE38KDEL role in promoting cell apoptosis in A375 and B16-F10 cells, and upregulation of MC1R endowed α-MSH-PE38KDEL function to promote cell apoptosis in MDA-MB-231 and HEMa cells. Additionally, α-MSH-PE38KDEL treatment increased the phosphorylation levels of Erk1/2 and MITF (S73), and decreased MITF and TYR expressions in an MC1R-dependent manner. All of the treatments, including inhibition of Erk1/2 with PD98059, MC1R downregulation and MITF overexpression weakened the anti-tumor role of α-MSH-PE38KDEL in melanoma. CONCLUSION: Collectively, this study indicates that α-MSH-PE38KDEL promotes melanoma cell apoptosis via modulating Erk1/2/MITF/TYR signaling in an MC1R-dependent manner.

Improving cell survival and engraftment in vivo via layer-by-layer nanocoating of hESC-derived RPE cells.

BACKGROUND: Human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cell transplants have served as a cell therapy for treating retinal degenerative diseases. However, how to optimize the survival and engraftment of hESC-RPE cells is a great challenge. METHODS: Here, we report hESC-RPE cells that are embedded with polyelectrolytes gelatin and alginate by layer-by-layer (LbL) self-assembly technique, based on the opposite charge of alternate layers. Cells were assessed for cell survival, immunogenicity, and function in vitro and in vivo. RESULTS: This strategy obviously decreased the immunogenicity of hESC-RPE cells without affecting its activity. LbL-RPE cell transplants into the subretinal space of Royal College of Surgeons (RCS) rats optimized cell engraftment and decreased immunogenicity compared to untreated RPE cell transplants (immunosuppression was not used during the 21-week study). Visual-functional assay with electroretinogram recordings (ERGs) also showed higher B wave amplitudes in RCS rats with LbL-RPE cell transplants. CONCLUSIONS: We demonstrate that transplanted LbL-RPE cells have better viability and grafting efficiency, optimized immunogenicity, and visual function. Therefore, LbL engineering is a promising method to increase the efficacy of hESC-RPE cell transplantation.

Comparison of acalabrutinib plus obinutuzumab, ibrutinib plus obinutuzumab and venetoclax plus obinutuzumab for untreated CLL: a network meta-analysis.

The optimal chemotherapy-free regimens for treatment-naive CLL still remains undefined. We searched relevant published reports. Three trials with 1017 subjects were identified. In the network meta-analysis, acalabrutinib plus obinutuzumab (Aca + Obi) improved PFS than ibrutinib plus obinutuzumab (Ibu + Obi) (HR:0.43, p = .02) and venetoclax plus obinutuzumab (Ven + Obi) (HR:0.30, p < .001) as IRC assessment. Sensitivity analysis of investigator assessment also showed improved PFS with Aca + Obi than Ibu + Obi (HR:0.46, p = .04) and Ven + Obi (HR:0.34, p = .002). Among these first-line treatments (Aca + Obi, Ibu + Obi, Ven + Obi and chlorambucil plus obinutuzumab (Chl + Obi)), Aca + Obi regimen had the highest probability of 99.1% (IRC assessment) or 98.0% (investigator assessment) to reach the longest PFS. The survival advantage with Aca + Obi was not statistically significant, compared to Ibu + Obi (HR:0.51, p = .21) and Ven + Obi (HR:0.38, p = .07). No significant difference was found in AEs analysis. Our data indicated that Aca + Obi seemed to prolong the PFS than Ibu + Obi and Ven + Obi. Considering our limits, prospective clinical trials directly comparing these regimens are warranted.