The impact of communication training on the clinical care of hypertension in general practice: a cluster randomized controlled trial in China.

BACKGROUND: Hypertension is one of the most common chronic diseases with a low control rate globally. The effect of communication skills training contributing to hypertension control remains uncertain. The aim of the present study was to assess the effectiveness of an educational intervention based on the Calgary-Cambridge guide in improving hypertensive management. METHODS: A cluster randomized controlled trial enrolled 27 general practitioners (GPs) and 540 uncontrolled hypertensive patients attending 6 community health centers in Chengdu, China. GPs allocated to the intervention group were trained by an online communication course and two face-to-face workshops based on Calgary-Cambridge guides. The primary outcome was blood pressure (BP) control rates and reductions in systolic and diastolic BP from baseline to 3 months. The secondary outcome was changes in GPs' communication skills after one month, patients' knowledge and satisfaction after 3 months. Bivariate analysis and the regression model assessed whether the health provider training improved outcomes. RESULTS: After the communication training, the BP control rate was significantly higher (57.2% vs. 37.4%, p < 0.001) in the intervention groups. Compared to the control group, there was a significant improvement in GP's communication skills (13.0 vs 17.5, p < 0.001), hypertensive patients' knowledge (18.0 vs 20.0, p < 0.001), and systolic blood pressure (139.1 vs 134.7, p < 0.001) after 3 months of follow-up. Random effects least squares regression models showed significant interactions between the intervention group and time period in the change of GP's communication skills (Parameter Estimated (PE): 0.612, CI:0.310,0.907, p = 0.006), hypertensive patient's knowledge (PE:0.233, CI: 0.098, 0.514, p < 0.001), satisfaction (PE:0.495, CI: 0.116, 0.706, p = 0.004), SBP (PE:-0.803, CI: -1.327, -0.389, p < 0.001) and DBP (PE:-0.918, CI: -1.694, -0.634, p < 0.001), from baseline to follow-up. CONCLUSION: Communication training based on the Calgary-Cambridge guide for GPs has shown to be an efficient way in the short term to improve patient-provider communication skills and hypertension outcomes among patients with uncontrolled BPs. TRIAL REGISTRATION: The trial was registered on Chinese Clinical Trials Registry on 2019-04-03. (ChiCTR1900022278).

Lovastatin impairs cellular proliferation and enhances hyaluronic acid production in fibroblast-like synoviocytes.

INTRODUCTION: Statins have demonstrated chondroprotective effects by reducing inflammation and mitigating extracellular matrix degradation. However, statins are also reported to be cytotoxic to several types of cells. Early-onset osteoarthritis (OA) is characterized by synovial inflammation, which adversely affects hyaluronan (HA) production in fibroblast-like synoviocytes (FLSs). Nevertheless, the precise effects of statins on the synovium remain unclear. METHODS: This study investigated the impact of lovastatin on human FLSs, and HA secretion-related genes, signaling pathways, and production were evaluated. RESULTS: The findings revealed that high doses of lovastatin (20 or 40 µM) decreased FLS viability and increased cell death. FLS proliferation ceased when cultured in a medium containing 5 or 10 µM lovastatin. mRNA expression analysis demonstrated that lovastatin (5 and 10 µM) upregulated the gene level of hyaluronan synthase 1 (HAS1), HAS2, and proteoglycan 4 (PRG4), but not HAS3. While the expression of multidrug resistance-associated protein 5 transporter gene remained unaffected, both inward-rectifying potassium channel and acid-sensing ion channel 3 were upregulated. Western blot further confirmed that lovastatin increased the production of HAS1 and PRG4, and activated the PKC-α, ERK1/2, and p38-MAPK signaling pathways. Additionally, lovastatin elevated intracellular cAMP levels and HA production in FLSs. CONCLUSION: Lovastatin impairs cellular proliferation but enhances HA production in human FLSs.

Single-cell disulfidptosis regulator patterns guide intercellular communication of tumor microenvironment that contribute to kidney renal clear cell carcinoma progression and immunotherapy.

Background: Disulfidptosis, an emerging type of programmed cell death, plays a pivotal role in various cancer types, notably impacting the progression of kidney renal clear cell carcinoma (KIRC) through the tumor microenvironment (TME). However, the specific involvement of disulfidptosis within the TME remains elusive. Methods: Analyzing 41,784 single cells obtained from seven samples of KIRC through single-cell RNA sequencing (scRNA-seq), this study employed nonnegative matrix factorization (NMF) to assess 24 disulfidptosis regulators. Pseudotime analysis, intercellular communication mapping, determination of transcription factor activities (TFs), and metabolic profiling of the TME subgroup in KIRC were conducted using Monocle, CellChat, SCENIC, and scMetabolism. Additionally, public cohorts were utilized to predict prognosis and immune responses within the TME subgroup of KIRC. Results: Through NMF clustering and differential expression marker genes, fibroblasts, macrophages, monocytes, T cells, and B cells were categorized into four to six distinct subgroups. Furthermore, this investigation revealed the correlation between disulfidptosis regulatory factors and the biological traits, as well as the pseudotime trajectories of TME subgroups. Notably, disulfidptosis-mediated TME subgroups (DSTN+CD4T-C1 and FLNA+CD4T-C2) demonstrated significant prognostic value and immune responses in patients with KIRC. Multiple immunohistochemistry (mIHC) assays identified marker expression within both cell clusters. Moreover, CellChat analysis unveiled diverse and extensive interactions between disulfidptosis-mediated TME subgroups and tumor epithelial cells, highlighting the TNFSF12-TNFRSF12A ligand-receptor pair as mediators between DSTN+CD4T-C1, FLNA+CD4T-C2, and epithelial cells. Conclusion: Our study sheds light on the role of disulfidptosis-mediated intercellular communication in regulating the biological characteristics of the TME. These findings offer valuable insights for patients with KIRC, potentially guiding personalized immunotherapy approaches.

Heterogeneity of computational pathomic signature predicts drug resistance and intra-tumor heterogeneity of ovarian cancer.

BACKGROUND: Chemotherapy resistance is the main cause of ovarian cancer progression and even death. However, there are no clear indicators for predicting the risk of drug resistance in patients. Intra-tumor heterogeneity (ITH) is one of the characteristics of malignant tumors, which is associated with the treatment and prognosis of tumors. Accordingly, our study aims to investigate the correlation between the image features of intra-tumor heterogeneity and drug resistance of ovarian cancer based on artificial intelligence. METHODS: We obtained hematoxylin and eosin staining frozen histopathological images of ovarian cancer and paracarcinoma tissues from the Cancer Genome Atlas. We extracted quantitative image features of whole-slide images based on the automatic image nuclear segmentation processing technology. After that, we used bioinformatics analysis to find the relationship between image features of intra-tumor heterogeneity and drug resistance. RESULTS: Our results show that our automatic image processing process based on computer artificial intelligence can extract image features effectively, and the key image features extracted are closely related to ITH. Among them, the Perimeter.sd image feature with the most prominent ITH feature can accurately predict the risk of platinum-based chemotherapy drug resistance in ovarian cancer patients. CONCLUSION: Automatic image processing and feature extraction based on artificial intelligence have excellent results. Perimeter.sd can be used as a useful image feature indicator for evaluating ITH. ITH is associated with drug resistance of ovarian cancer, so ITH characteristics can be used as an effective indicator to evaluate drug resistance in patients with ovarian cancer.

Icariin improves cardiac function and remodeling via the TGF-ß1/Smad signaling pathway in rats following myocardial infarction.

BACKGROUND: Postinfarction cardiac remodeling presents a compensatory mechanism aimed at mitigating congestive heart failure. It is distinguished by progressive dilatation and hypertrophy of the ventricular chambers, fibrotic alterations, and prolonged apoptosis of cardiomyocytes. The primary objective of this study was to assess the effects of icariin on myocardial fibrosis and ventricular remodeling in rats subjected to myocardial infarction (MI). METHODS: Male Sprague‒Dawley (SD) rats were subjected to randomization and subsequently divided into distinct groups: the control group, the sham group (undergoing sham operation), the MI group (experiencing ligation of the left anterior descending artery), and the icariin group. Within the icariin group, rats were further categorized into three different dose groups based on the administered icariin dosage: the MI30 group (30 mg/kg/day), the MI60 group (60 mg/kg/day), and the MI120 group (120 mg/kg/day). Cardiac function evaluation was carried out using echocardiography. Histological examinations, including hematoxylin and eosin (HE) staining, Masson staining, and immunohistochemistry studies, were conducted 90 days after the occurrence of MI. Additionally, Western blotting was employed to assess TGF-ß1, p-Smad2, and p-Smad3 levels. RESULTS: The administration of icariin revealed a noteworthy enhancement in cardiac function among rats afflicted with left anterior descending coronary artery (LAD) ligation. In comparison to the icariin groups, the MI group exhibited reduced EF and FS, along with elevated LVEDD and LVESD. Furthermore, the cardiac fibrosis levels in the MI group rats exhibited a considerable increase compared to those in the icariin group. Notably, the levels of Collagen I, Collagen III, MMP2, and MMP9 were significantly higher in the MI group than in the icariin group, with evident distinctions. Moreover, the expression levels of TGF-ß, IL-13, p-Smad2, and p-Smad3 were notably upregulated in the MI group compared to the icariin group. CONCLUSIONS: In an experimental rat model of MI, the administration of icariin resulted in the amelioration of both cardiac function and remodeling processes, operating through the intricate TGF-ß1/Smad signaling pathway.

Validation of the ICEBERG emergency room screening tool for early identification of older patients with geriatric consultation needs.

Background: The growing number of older and oldest-old patients often present in the emergency room (ER) with undiagnosed geriatric syndromes posing them at high risk for complications in acute care. Objective: To develop and validate an ER screening tool (ICEBERG) to capture 9 geriatric domains of risk in older patients. Design setting and participants: For construct validity we performed a chart-based study in 129 ER patients age 70 years and older admitted to acute geriatric care (pilot 1). For criterion validity we performed a prospective study in 288 ER patients age 70 years and older admitted to acute care (pilot 2). Exposure: In both validation steps, the exposure was ICEBERG test performance below and above the median score (10, range 0-30). Outcome measures and analysis: In pilot 1, we compared the exposure with results of nine tests of the Comprehensive Geriatric Assessment (CGA). In pilot 2, we compared the exposure assessed in the ER to following length of hospital stay (LOS), one-on-one nursing care needs, in-hospital mortality, 30-day re-admission rate, and discharge to a nursing home. Main results: Mean age was 82.9 years (SD 6.7; n = 129) in pilot 1, and 81.5 years (SD 7.0; n = 288) in pilot 2. In pilot 1, scoring ≥10 was associated with significantly worse performance in 8 of 9 of the individual CGA tests. In pilot 2, scoring ≥10 resulted in longer average LOS (median 7 days, IQR 4, 11 vs. 6 days, IQR 3, 8) and higher nursing care needs (median 1,838 min, IQR 901, 4,267 vs. median 1,393 min, IQR 743, 2,390). Scoring ≥10 also increased the odds of one-on-one nursing care 2.9-fold (OR 2.86, 95%CI 1.17-6.98), and the odds of discharge to a nursing home 3.7-fold (OR 3.70, 95%CI 1.74-7.85). Further, scoring ≥10 was associated with higher in-hospital mortality and re-hospitalization rates, however not reaching statistical significance. Average time to complete the ICEBERG tool was 4.3 min (SD 1.3). Conclusion: Our validation studies support construct validity of the ICEBERG tool with the CGA, and criterion validity with several clinical indicators in acute care.

Biomineralized Polydopamine Nanoparticle-Based Sodium Alginate Hydrogels for Delivery of Anti-serine/Threonine Protein Kinase B-Rapidly Accelerated Fibrosarcoma siRNA for Metastatic Melanoma Therapy.

Malignant melanoma, as a highly aggressive skin cancer, is strongly associated with mutations in serine/threonine protein kinase B-RAF (BRAF, where RAF stands for rapidly accelerated fibrosarcoma). Targeted therapy with anti-BRAF small interfering RNA (siBRAF) represents a crucial aspect of metastatic melanoma treatment. In this study, an injectable hydrogel platform based on sodium alginate (SA), with multifunctions of photothermal and Ca2+-overload cell apoptosis, was explored as a siBRAF carrier for metastatic melanoma therapy. We employed polydopamine nanoparticles (PDAs) as a photothermal core and constructed a calcium phosphate (CaP) shell via biomineralization (PDA@CaP) to load siBRAF (PDA@siBRAF/CaP). The pH-sensitive CaP shell facilitated the release of Ca2+ under the weakly acidic tumor microenvironment, triggering the gelation of PDA@siBRAF/CaP-SA to localized release siBRAF at tumor sites with the interruption of the RAS-RAF-MEK-ERK (MAPK) pathway. Besides, the continuous release of Ca2+ could also lead to Ca2+-overload cell apoptosis. Moreover, the photothermal effect of PDA regulated the release kinetics, resulting in coordinated therapeutic abilities of individual components in the PDA@siBRAF/CaP-SA hydrogels. Consequently, the effective inhibition of tumor growth and metastasis was achieved in vitro and in vivo using a highly metastatic melanoma cell line B16F10 as the model, by combining photothermal ablation, Ca2+ overload, and BRAF silencing. Our work provides a proof-of-concept for an injectable hydrogel system that simultaneously targets multiple mechanisms involved in melanoma progression and has the potential to be translated into clinical use for the metastatic melanoma therapy.

SIRT3-mediated autophagy contributes to ferroptosis-induced anticancer by inducing the formation of BECN1-SLC7A11 complex.

Ferroptosis is an autophagy-dependent cell death associated with iron accumulation and lipid peroxidation, which plays a crucial part in anticancer activity. Sirtuin 3 (SIRT3) positively regulates autophagy by phosphorylation of activated protein kinase (AMPK). However, whether SIRT3-mediated autophagy can inhibit the cystine/glutamate antiporter (system Xc-) activity by inducing the formation of a BECN1-SLC7A11 complex and consequently promote induction of ferroptosis is unknown. Using both in vitro and in vivo models, we revealed that combination treatment with erastin and TGF-ß1 decreased the expression of epithelial-mesenchymal transition-related markers and inhibited the invasion and metastasis of breast cancer. Furthermore, TGF-ß1 promoted erastin-induced ferroptosis-related indicators in MCF-7 cells and tumor-bearing nude mice models. Interestingly, the expression of SIRT3, p-AMPK, and autophagy-related markers were significantly elevated after co-treatment with erastin and TGF-ß1, suggesting that combination treatment of erastin and TGF-ß1 mediated autophagy by the SIRT3/AMPK signaling pathway. In addition, erastin-induced BECN1-SLC7A11 complexes were more abundant after co-treatment with TGF-ß1. This effect was inhibited by the autophagy inhibitor 3-methyladenine or siSIRT3, further revealing that combination treatment of erastin and TGF-ß1 mediated autophagy-dependent ferroptosis by inducing the formation of BECN1-SLC7A11 complexes. Our results agreed with the concept that BECN1 directly binds to SLC7A11 to inhibit system Xc- activity. In summary, our studies confirmed that SIRT3-mediated autophagy is conducive to ferroptosis-mediated anticancer activity by inducing the formation of BECN1-SLC7A11 complexes, which is a potential therapeutic approach for treating breast cancer.

Expert Consensus on the Diagnosis and Treatment of Anticancer Drug-Induced Interstitial Lung Disease.

Drug-induced interstitial lung disease (DILD) is the most common pulmonary adverse event of anticancer drugs. In recent years, the incidence of anticancer DILD has gradually increased with the rapid development of novel anticancer agents. Due to the diverse clinical manifestations and the lack of specific diagnostic criteria, DILD is difficult to diagnose and may even become fatal if not treated properly. Herein, a multidisciplinary group of experts from oncology, respiratory, imaging, pharmacology, pathology, and radiology departments in China has reached the "expert consensus on the diagnosis and treatment of anticancer DILD" after several rounds of a comprehensive investigation. This consensus aims to improve the awareness of clinicians and provide recommendations for the early screening, diagnosis, and treatment of anticancer DILD. This consensus also emphasizes the importance of multidisciplinary collaboration while managing DILD.

The Potential Diagnostic Biomarkers for the IgG Subclass in Coal Workers' Pneumoconiosis.

Evidence suggests that exposure to coal dust increases immunoglobulin concentration. However, there is a paucity of data reporting immunoglobulin G (IgG) subclass in coal workers' pneumoconiosis (CWP). Therefore, this study intended to evaluate potential diagnostic biomarkers for the disease. CWP patients, dust-exposed workers without pneumoconiosis (DEW), and matched healthy controls (HCs) presented to the General Hospital of Datong Coal Mining Group and Occupational Disease Prevention and Treatment Hospital of Datong Coal Mining Group between May 2019 and September 2019 were recruited. The serum immunoglobulin concentration was determined by the multiplex immunoassay technique. Totally, 104 CWP patients, 109 DEWs, and 74 HCs were enrolled. Serum levels of IgG1, IgG2, IgM, and IgA were elevated in CWPs compared with those in DEWs and HCs (P < 0.05). The order of diagnostic accuracy between CWPs and DEWs depicted by the receiver operating characteristic (ROC) curve was IgG2, IgM, IgG1, IgG3, and IgA. Significantly higher IgG1/IgG3 and IgG2/IgG3 ratios were observed in the CWP group than in DEW and HC groups. Based on the IgG2/IgG3 ratio, the area under the ROC curve between CWP and DEW was 0.785 (95% CI 0.723-0.838), with a sensitivity of 73.1% and a specificity of 73.4%. Our findings suggest that IgG1, IgG2, IgM, and IgA are higher in the CWPs than DEWs and HCs. The IgG2/IgG3 ratio provides a viable alternative for the diagnosis of CWP.

Protecting Vaccine Safety: An Improved, Blockchain-Based, Storage-Efficient Scheme.

In recent years, vaccine safety incidents have occurred frequently. To protect vaccine safety, researchers have proposed to use blockchain to secure the vaccine circulation process. Technically, blockchain has some limitations in solving vaccine and other supply chain problems, such as large on-chain storage consumption and low throughput. To better alleviate these restrictions, we propose an improved, blockchain-based, storage-efficient vaccine safety protection scheme in this work. Specifically, we first model the vaccine circulation process. We then design a system to protect vaccine circulation using blockchain, cloud, and cryptographic mechanisms. The proposed system leverages the cloud to implement the vaccine circulation model. Correspondingly, it uses the blockchain to store circulating data certificates and signatures. We evaluated the proposed conceptual model using a consortium blockchain. The experimental results show that the proposed system is efficient.

Comparing albuvirtide plus ritonavir-boosted lopinavir regimen to two nucleotide reverse transcriptase inhibitors plus ritonavir-boosted lopinavir in HIV-infected individuals who failed initial treatment: a retrospective comparative cohort study.

Background: Albuvirtide (ABT), a fusion inhibitor against human immunodeficiency virus (HIV) infection, has good efficacy and tolerability for HIV treatment. However, there is a paucity of data regarding ABT-based regimen as second-line therapy. This current study evaluated the efficacy and safety of switching to ABT + ritonavir-boosted lopinavir (LPV/r) treatment in a cohort of HIV-infected individuals who failed initial treatment. Methods: This retrospective comparative cohort study included patients who failed initial treatment and switched to either ABT + LPV/r (the ABT group) or two nucleotide reverse transcriptase inhibitors (NRTIs) + LPV/r (the NRTI group) between November 2019 and December 2020 in the People's Hospital of Zhaojue County in Liangshan Yi Autonomous Prefecture, China. All individuals were followed up from baseline to 12 weeks after conversion, or until the patient developed unacceptable toxic effects or was loss of follow-up. The proportion of patients who achieved virological suppression (viral load <50 copies/mL) at week 12 was considered a primary efficacy endpoint. Safety outcomes included the incidence of adverse events and laboratory abnormalities. All participants underwent resistance testing before regimen conversion. The linear regression model was applied to evaluate the association of CD4+ T cell count with the patient's clinical characteristics. Results: A total of 71 patients were included in this study, the two groups were comparable at baseline in terms of age, sex, CD4+ T cell count, and viral load. The suppression of HIV-1 RNA to levels <50 copies/mL was achieved in 82.4% (28/31) and 29.7% (11/34) of patients in the ABT group and the NRTI group, respectively (P<0.001). Older age (P=0.016) and higher alkaline phosphatase (ALP) levels (P=0.038), but not rescue regimen, were associated with attenuated CD4+ T cell recovery. Most adverse events mild in severity, with abdominal pain as the most reported event in two groups (26.8%, 19/71), and no severe adverse events were detected. Conclusions: Conversion to ABT + LPV/r therapy appears to be an effective and safe strategy. This treatment regimen has great potential to be generalized in the HIV-infected population, although further testing in a larger patient population is required to verify these results.

Mediating Effect of Loneliness in the Relationship between Depressive Symptoms and Cognitive Frailty in Community-Dwelling Older Adults.

BACKGROUND: This study aims to explore the mediating role of loneliness between depressive symptoms and cognitive frailty among older adults in the community. METHODS: A total of 527 community-dwelling older adults aged ≥ 60 years were included in this cross-sectional study. A five-item geriatric depression scale was used to assess depression symptoms. Then, an eight-item University of California at Los Angeles Loneliness Scale was used to assess loneliness. Moreover, the FRAIL scale and Mini-Mental State Examination were used to assess cognitive frailty. Furthermore, regression and bootstrap analyses were used to explore the mediating role of loneliness in depression symptoms and cognitive frailty. RESULTS: Loneliness mediates the association between depression symptoms and cognitive frailty (95% CI = 0.164~0.615), and after adjusting for loneliness, the direct effect is no longer significant (95% CI = -0.113~1.318, p = 0.099). CONCLUSIONS: Results show that the effect of cognitive frailty is not depression symptoms but loneliness. All levels of society (the government, medical institutions, and communities) need to pay more attention to the mental health of the older adults, screen for loneliness, and take timely intervention and treatment measures. They should also build an age-friendly society and promote active aging.

A novel four-gene signature for predicting the prognosis of hepatocellular carcinoma.

OBJECTIVE: To identify and utilize gene signatures for the prognostic evaluation of postoperative patients with hepatocellular carcinoma (HCC). METHODS: The gene mRNA expression profiles and corresponding clinicopathological data of postoperative patients with HCC were downloaded from The Cancer Genome Atlas (TCGA) database. Highly differentially expressed genes (DEGs) in tumor tissues compared to adjacent tissues were identified, and their associations with the overall survival (OS) of HCC patients were analyzed. The strongly associated genes were used to develop a prognostic score for the survival stratification of HCC, and the underlying mechanisms were analyzed using bioinformatics. RESULTS: A total of 376 DEGs were identified and four DEGs (ADH4, COL15A1, RET and KCNJ16) were independently associated with OS. A prognostic score derived from the four genes could effectively stratify HCC patients with different OS outcomes, independent of clinical parameters. Patients with high scores exhibited poorer OS than patients with low scores (HR 5.526, 95% CI: 2.451-12.461, p < .001). The four genes were involved in cancer-related biological processes and were independent of each other in bioinformatics analyses. CONCLUSION: Four genes strongly associated with the prognosis of postoperative patients with HCC were identified, and the derived prognostic score was simple and valuable for overall survival prediction.

Metal ions/nucleotide coordinated nanoparticles comprehensively suppress tumor by synergizing ferroptosis with energy metabolism interference.

BACKGROUND: Ferroptosis holds promise as a potential tumor therapy by programming cell death with a hallmark of reactive oxygen species (ROS)-induced lipid peroxidation. However, vigorous energy metabolism may assist tumors to resist oxidative damage and thus weaken the effects of ferroptosis in tumor treatment. RESULTS: Herein, a bifunctional antitumor platform was constructed via coordinated interactions between metal ions and nucleotides to synergistically activate ferroptosis and interrupt energy metabolism for tumor therapy. The designed nanoparticles were composed of Fe2+/small interfering RNA (siRNA) as the core and polydopamine as the cloak, which responded to the tumor microenvironment with structural dissociation, thereby permitting tumor-specific Fe2+ and siRNA release. The over-loaded Fe2+ ions in the tumor cells then triggered ferroptosis, with hallmarks of lipid peroxidation and cellular glutathione peroxidase 4 (GPX4) down-regulation. Simultaneously, the released siRNA targeted and down-regulated glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression in the tumor to inhibit glycolytic pathway, which interfered with tumor energy metabolism and enhanced Fe2+-induced ferroptosis to kill tumor cells. CONCLUSIONS: This study presents a concise fabrication of a metal ion/nucleotide-based platform to integrate ferroptosis and energy metabolism intervention in one vehicle, thereby providing a promising combination modality for anticancer therapy.

Modular, robust, and extendible multicellular circuit design in yeast.

Division of labor between cells is ubiquitous in biology but the use of multicellular consortia for engineering applications is only beginning to be explored. A significant advantage of multicellular circuits is their potential to be modular with respect to composition but this claim has not yet been extensively tested using experiments and quantitative modeling. Here, we construct a library of 24 yeast strains capable of sending, receiving or responding to three molecular signals, characterize them experimentally and build quantitative models of their input-output relationships. We then compose these strains into two- and three-strain cascades as well as a four-strain bistable switch and show that experimentally measured consortia dynamics can be predicted from the models of the constituent parts. To further explore the achievable range of behaviors, we perform a fully automated computational search over all two-, three-, and four-strain consortia to identify combinations that realize target behaviors including logic gates, band-pass filters, and time pulses. Strain combinations that are predicted to map onto a target behavior are further computationally optimized and then experimentally tested. Experiments closely track computational predictions. The high reliability of these model descriptions further strengthens the feasibility and highlights the potential for distributed computing in synthetic biology.

Safety and accuracy of transbronchial lung cryobiopsy in diagnosing desquamative interstitial pneumonia.

INTRODUCTION: Transbronchial lung cryobiopsy (TBLC) is a new technique to obtain specimens for diagnosis of interstitial lung disease (ILD) in recent years. The objective of this study is to evaluate the safety and the diagnostic accuracy of TBLC in patients of desquamative interstitial pneumonia (DIP). METHODS: In this study twelve patients confirmed with DIP were selected from January 2019 to December 2020 at the department of pulmonary and critical care medicine in China-Japan Friendship Hospital. All cases underwent TBLC in a hybrid cone beam CT (CBCT) operation room with a single general anesthesia. The definitive diagnosis was made by a multidisciplinary team that involved clinicians, radiologists and pathologists. This study analyzed the biopsy sample surface areas, main complications and the consistency between TBLC pathology and multidisciplinary discussion (MDD) diagnosis for DIP. RESULTS: An average of 3.1 ± 1.1 specimens were obtained per patient. The mean surface area of the specimen was 23.7 ± 6.1 mm2 . None of the cases had pneumothorax or massive hemorrhage. Ten cases (83.3%) had no or mild bleeding and two cases (16.7%) had moderate bleeding. All cases had the typical pathologic characteristics of DIP, which was highly consistent with the diagnosis of MDD. CONCLUSION: TBLC can obtain sufficient samples for the pathological diagnosis of DIP, which has high security and accuracy in experienced specialist centers.

Higher viral load and infectivity increase risk of aerosol transmission for Delta and Omicron variants of SARS-CoV-2.

BACKGROUND: Airborne transmission of SARS-CoV-2 is an important route of infection. For the wildtype (WT) only a small proportion of those infected emitted large quantities of the virus. The currently prevalent variants of concern, Delta (B1.617.2) and Omicron (B.1.1.529), are characterized by higher viral loads and a lower minimal infective dose compared to the WT. We aimed to describe the resulting distribution of airborne viral emissions and to reassess the risk estimates for public settings given the higher viral load and infectivity. METHOD: We reran the Monte Carlo modelling to estimate viral emissions in the fine aerosol size range using available viral load data. We also updated our tool to simulate indoor airborne transmission of SARS-CoV-2 by including a CO2 calculator and recirculating air cleaning devices. We also assessed the consequences of the lower critical dose on the infection risk in public settings with different protection strategies. RESULTS: Our modelling suggests that a much larger proportion of individuals infected with the new variants are high, very high or super-emitters of airborne viruses: for the WT, one in 1,000 infected was a super-emitter; for Delta one in 30; and for Omicron one in 20 or one in 10, depending on the viral load estimate used. Testing of the effectiveness of protective strategies in view of the lower critical dose suggests that surgical masks are no longer sufficient in most public settings, while correctly fitted FFP2 respirators still provide sufficient protection, except in high aerosol producing situations such as singing or shouting. DISCUSSION: From an aerosol transmission perspective, the shift towards a larger proportion of very high emitting individuals, together with the strongly reduced critical dose, seem to be two important drivers of the aerosol risk, and are likely contributing to the observed rapid spread of the Delta and Omicron variants of concern. Reducing contacts, always wearing well-fitted FFP2 respirators when indoors, using ventilation and other methods to reduce airborne virus concentrations, and avoiding situations with loud voices seem critical to limiting these latest waves of the COVID-19 pandemic.

Construction of a prognostic assessment model for colon cancer patients based on immune-related genes and exploration of related immune characteristics.

Objectives: To establish a novel risk score model that could predict the survival and immune response of patients with colon cancer. Methods: We used The Cancer Genome Atlas (TCGA) database to get mRNA expression profile data, corresponding clinical information and somatic mutation data of patients with colon cancer. Limma R software package and univariate Cox regression were performed to screen out immune-related prognostic genes. GO (Gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) were used for gene function enrichment analysis. The risk scoring model was established by Lasso regression and multivariate Cox regression. CIBERSORT was conducted to estimate 22 types of tumor-infiltrating immune cells and immune cell functions in tumors. Correlation analysis was used to demonstrate the relationship between the risk score and immune escape potential. Results: 679 immune-related genes were selected from 7846 differentially expressed genes (DEGs). GO and KEGG analysis found that immune-related DEGs were mainly enriched in immune response, complement activation, cytokine-cytokine receptor interaction and so on. Finally, we established a 3 immune-related genes risk scoring model, which was the accurate independent predictor of overall survival (OS) in colon cancer. Correlation analysis indicated that there were significant differences in T cell exclusion potential in low-risk and high-risk groups. Conclusion: The immune-related gene risk scoring model could contribute to predicting the clinical outcome of patients with colon cancer.