Synthetic biology approaches for improving the specificity and efficacy of cancer immunotherapy.

Immunotherapy has shown robust efficacy in treating a broad spectrum of hematological and solid cancers. Despite the transformative impact of immunotherapy on cancer treatment, several outstanding challenges remain. These challenges include on-target off-tumor toxicity, systemic toxicity, and the complexity of achieving potent and sustainable therapeutic efficacy. Synthetic biology has emerged as a promising approach to overcome these obstacles, offering innovative tools for engineering living cells with customized functions. This review provides an overview of the current landscape and future prospects of cancer immunotherapy, particularly emphasizing the role of synthetic biology in augmenting its specificity, controllability, and efficacy. We delineate and discuss two principal synthetic biology strategies: those targeting tumor surface antigens with engineered immune cells and those detecting intratumoral disease signatures with engineered gene circuits. This review concludes with a forward-looking perspective on the enduring challenges in cancer immunotherapy and the potential breakthroughs that synthetic biology may contribute to the field.

Affinity fine-tuning anti-CAIX CAR-T cells mitigate on-target off-tumor side effects.

One of the major hurdles that has hindered the success of chimeric antigen receptor (CAR) T cell therapies against solid tumors is on-target off-tumor (OTOT) toxicity due to sharing of the same epitopes on normal tissues. To elevate the safety profile of CAR-T cells, an affinity/avidity fine-tuned CAR was designed enabling CAR-T cell activation only in the presence of a highly expressed tumor associated antigen (TAA) but not when recognizing the same antigen at a physiological level on healthy cells. Using direct stochastic optical reconstruction microscopy (dSTORM) which provides single-molecule resolution, and flow cytometry, we identified high carbonic anhydrase IX (CAIX) density on clear cell renal cell carcinoma (ccRCC) patient samples and low-density expression on healthy bile duct tissues. A Tet-On doxycycline-inducible CAIX expressing cell line was established to mimic various CAIX densities, providing coverage from CAIX-high skrc-59 tumor cells to CAIX-low MMNK-1 cholangiocytes. Assessing the killing of CAR-T cells, we demonstrated that low-affinity/high-avidity fine-tuned G9 CAR-T has a wider therapeutic window compared to high-affinity/high-avidity G250 that was used in the first anti-CAIX CAR-T clinical trial but displayed serious OTOT effects. To assess the therapeutic effect of G9 on patient samples, we generated ccRCC patient derived organotypic tumor spheroid (PDOTS) ex vivo cultures and demonstrated that G9 CAR-T cells exhibited superior efficacy, migration and cytokine release in these miniature tumors. Moreover, in an RCC orthotopic mouse model, G9 CAR-T cells showed enhanced tumor control compared to G250. In summary, G9 has successfully mitigated OTOT side effects and in doing so has made CAIX a druggable immunotherapeutic target.

Decoupling NAD+ metabolic dependency in chondrosarcoma by targeting the SIRT1-HIF-2α axis.

Chondrosarcomas represent the second most common primary bone malignancy. Despite the vulnerability of chondrosarcoma cells to nicotinamide adenine dinucleotide (NAD+) depletion, targeting the NAD+ synthesis pathway remains challenging due to broad implications in biological processes. Here, we establish SIRT1 as a central mediator reinforcing the dependency of chondrosarcoma cells on NAD+ metabolism via HIF-2α-mediated transcriptional reprogramming. SIRT1 knockdown abolishes aggressive phenotypes of chondrosarcomas in orthotopically transplanted tumors in mice. Chondrosarcoma cells thrive under glucose starvation by accumulating NAD+ and subsequently activating the SIRT1-HIF-2α axis. Decoupling this link via SIRT1 inhibition unleashes apoptosis and suppresses tumor progression in conjunction with chemotherapy. Unsupervised clustering analysis identifies a high-risk chondrosarcoma patient subgroup characterized by the upregulation of NAD+ biosynthesis genes. Finally, SIRT1 inhibition abolishes HIF-2α transcriptional activity and sensitizes chondrosarcoma cells to doxorubicin-induced cytotoxicity, irrespective of underlying pathways to accumulate intracellular NAD+. We provide system-level guidelines to develop therapeutic strategies for chondrosarcomas.

Trade-off between local replication and long-distance dissemination during experimental evolution of a satellite RNA.

Satellite RNAs (satRNAs) are molecular parasites that depend on their non-homologous helper viruses (HVs) for essential biological functions. While there are multiple molecular and phylogenetic studies on satRNAs, there is no experimental evolution study on how satRNAs may evolve in common infection conditions. In this study, we serially passaged the Bamboo mosaic virus (BaMV) associated-satRNA (satBaMV) under conditions in which satBaMV either coinfects an uninfected host plant, Nicotiana benthamiana, with BaMV or superinfects a transgenic N. benthamiana expressing the full-length BaMV genome. Single-nucleotide polymorphisms (SNPs) of satBaMV populations were analyzed by deep sequencing. Forty-eight SNPs were identified across four different experimental treatments. Most SNPs are treatment-specific, and some are also ephemeral. However, mutations at positions 30, 34, 63, and 82, all located at the 5' untranslated region (UTR), are universal in all treatments. These universal SNPs are configured into several haplotypes and follow different population dynamics. We constructed isogenic satBaMV strains only differing at positions 30 and 82 and conducted competition experiments in protoplasts and host plants. We found that the haplotype that reached high frequency in protoplasts and inoculation leaves also exhibited poor dissemination to systemic leaves and vice versa, thus suggesting an apparent trade-off between local replication and long-distance dissemination. We posit that the trade-off is likely caused by antagonistic pleiotropy at the 5' UTR. Our findings revealed a hitherto under-explored connection between satRNA genome replication and movement within a host plant. The significance of such a connection during satRNA evolution warrants a more thorough investigation.

A review of tamoxifen administration regimen optimization for Cre/loxp system in mouse bone study.

Gene knockout is a technique routinely used in basic experimental research, particularly in mouse skeletal and developmental studies. Tamoxifen-induced Cre/loxp system is known for its temporal and spatial precision and commonly utilized by researchers. However, tamoxifen has been shown its side effects on affecting the phenotype of mouse bone directly. This review aimed to optimize tamoxifen administration regimens including its dosage and duration, to identify an optimal induction strategy that minimizes potential side effects while maintaining recombination efficacy. This study will help researchers in designing gene knockout experiments in bone when using tamoxifen.

Gender differences among long-stay inpatients with schizophrenia in China: A cross-sectional study.

Objective: We sought to examine the independent correlates of long-term hospitalization in a sample of Chinese inpatients with schizophrenia (SCZ) from a gender-based perspective. Methods: This was a cross-sectional study that was carried out in a tertiary psychiatric hospital. All adult inpatients in this hospital were screened from January to March 2020, 251 of whom were identified as long-stay inpatients with SCZ (LSIS) and 224 as short-stay inpatients with SCZ (SSIS). Demographic and clinical information of the two groups was collected through medical records, scale assessments and interviews. Gender differences were analyzed, and independent correlates of long-stay between genders were explored by logistic regression analyses. Results: Compared to SSIS, greater proportions of LSIS patients were male (64.1%), single (82.1%), unemployed (81.7%) and had no family caregivers (54.2%). For LSIS per se, proportionally more males were single (88.8%), had no family caregiver (65.8%), had concomitant physical disease (65.2%) and had a history of hazardous behavior (27.3%) than their female counterparts. For females, the top independent risk factors for a long stay included poor functioning (OR = 5.9, 95% CI: 2.9-12.0), older age (OR = 4.3, 95% CI: 2.1-9.1) and being single (OR = 3.9, 95% CI: 1.8-8.4). Similar to women, both older age (OR = 5.3, 95% CI: 2.5-11.2) and poor functioning (OR = 4.0, 95% CI: 2.1-7.9) were also independent factors for long-term hospitalization of male patients; however, having no family caregiver (OR = 10.2, 95% CI: 4.6-22.6) was the primary risk factor for men. Conclusions: Both clinical and nonclinical factors play important roles in long-term hospitalization in Chinese patients with schizophrenia. There are overlaps and distinctions across genders with respect to the independent factors of long stays. These findings provide clues for developing better service strategies for this population, and highlight the importance of paying attention to gender differences in further research in this field.

[Identification of terpene synthase gene family in Gynostemma pentaphyllum and expression pattern analysis under abiotic stresses].

The present study aimed to investigate the composition of the terpene synthase(TPS) gene family in Gynostemma pentaphyllum and its role in abiotic stresses. The G. pentaphyllum TPS gene family was identified and analyzed at the genome-wide level using bioinformatics analysis, and the expression patterns of these family members were analyzed in different tissues of G. pentaphyllum as well as under various abiotic stresses. The results showed that there were 24 TPS gene family members in G. pentaphyllum with protein lengths ranging from 294 to 842 aa. All of them were localized in the cytoplasm or chloroplasts and unevenly distributed on the 11 chromosomes of G. pentaphyllum. The results of the phylogenetic tree showed that the G. pentaphyllum TPS gene family members could be divided into five subfamilies. As revealed by the analysis of promoter cis-acting elements, TPS gene family members in G. pentaphyllum were predicted to respond to a variety of abiotic stresses such as salt, low temperature, and dark stress. The analysis of gene expression patterns in different tissues of G. pentaphyllum revealed that nine TPS genes were tissue-specific in expression. The qPCR results showed that GpTPS16, GpTPS17, and GpTPS21 responded to a variety of abiotic stresses. This study is expected to provide references in guiding the further exploration of the biological functions of G. pentaphyllum TPS genes under abiotic stresses.

Cumulative sum analysis of the learning curve of laparoendoscopic single-site robot-assisted radical prostatectomy.

BACKGROUND: Radical prostatectomy has become the gold standard for treating localized prostate cancer. Improvement in the single-site technique and surgeon's skill reduces not only the hospital duration but also the number of wounds. Realizing the learning curve for a new procedure can prevent unnecessary mistakes. OBJECTIVE: To analyze the learning curve of extraperitoneal laparoendoscopic single-site robot-assisted radical prostatectomy (LESS-RaRP). METHODS: We retrospectively evaluated 160 patients diagnosed with prostate cancer during June 2016 to December 2020 who underwent extraperitoneal LESS-RaRP. Calculated cumulative sum analysis (CUSUM) was used to evaluate the learning curves for the extraperitoneal setting time, robotic console time, total operation time, and blood loss. The operative and functional outcomes were also assessed. RESULTS: The learning curve of the total operation time was observed in 79 cases. For the extraperitoneal setting and robotic console times, the learning curve was observed in 87 and 76 cases, respectively. The learning curve for blood loss was observed in 36 cases. No in-hospital mortality or respiratory failure was observed. CONCLUSION: Extraperitoneal LESS-RaRP using the da Vinci Si system is safe and feasible. Approximately 80 patients are required to achieve a stable and consistent operative time. A learning curve for blood loss was observed after 36 cases.

The COVID-19 vaccine did not affect the basal immune response and menstruation in female athletes.

The COVID-19 pandemic restricted the regular training and competition program of athletes. Vaccines against COVID-19 are known to be beneficial for the disease; however, the unknown side effects of vaccines and postvaccination reactions have made some athletes hesitant to get vaccinated. We investigated the changes in inflammatory responses and menstrual cycles of female athletes before and after vaccination. Twenty female athletes were enrolled in this study. Blood was collected from each subject before the first COVID-19 vaccination and after the first and second vaccinations. Laboratory data, including white blood cell, neutrophil, lymphocyte, and platelet counts, and inflammatory markers, including NLR (neutrophil-to-lymphocyte ratio), PLR (platelet lymphocyte ratio), RPR (red cell distribution width to platelet ratio), SII (systemic immune-inflammation index), and NeuPla (neutrophil-platelet ratio), were analyzed statistically. The menstrual changes before and after vaccination and the side effects were collected by questionnaires. No significant changes in the laboratory data were found after the first and second shots when compared to those at prevaccination: white blood cell, neutrophil, lymphocyte, platelet, NLR, PLR, SII, RPR, and NeuPla (p > 0.05). In addition, there were no significant changes in the menstruation cycle or days of the menstrual period (p > 0.05). All side effects after vaccination were mild and subsided in 2 days. The blood cell counts, inflammatory markers, and menstruation of female athletes were not affected by COVID-19 vaccines.

Reduced SARS-CoV-2 infection risk is associated with the use of Seven-Flavor Herb Tea: A multi-center observational study in Shanghai, China / 中西医结合学报

OBJECTIVE@#Omicron, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, is responsible for numerous infections in China. This study investigates the association between the use of Seven-Flavor Herb Tea (SFHT) and the risk of SARS-CoV-2 infection to develop precise and differentiated strategies for control of the coronavirus disease 2019 (COVID-19).@*METHODS@#This case-control study was conducted at shelter hospitals and quarantine hotels in China. A total of 5348 laboratory-confirmed COVID-19 patients were enrolled between April 1 and May 31, 2022, while 2190 uninfected individuals served as healthy controls. Structured questionnaires were used to collect data on demographics, underlying diseases, vaccination status, and use of SFHT. Patients were propensity-score-matched using 1:1 nearest-neighbor matching of the logit of the propensity score. Subsequently, a conditional logistic regression model was used for data analysis.@*RESULTS@#Overall, 7538 eligible subjects were recruited, with an average age of [45.54 ± 16.94] years. The age of COVID-19 patients was significantly higher than that of uninfected individuals ([48.25 ± 17.48] years vs [38.92 ± 13.41] years; t = 22.437, P < 0.001). A total of 2190 COVID-19 cases were matched with uninfected individuals at a 1:1 ratio. The use of SFHT (odds ratio = 0.753, 95% confidence interval: 0.692, 0.820) was associated with a lower risk of SARS-CoV-2 infection compared to untreated individuals.@*CONCLUSION@#Our findings suggest that taking SFHT reduces the risk of SARS-CoV-2 infection. This is a useful study in the larger picture of COVID-19 management, but data from large-sample multi-center, randomized clinical trial are warranted to confirm the finding. Please cite this article as: Zhang SX, Chen XX, Zheng Y, Cai BH, Shi W, Ru M, Li H, Zhang DD, Tian Y, Chen YL. Reduced SARS-CoV-2 infection risk is associated with the use of Seven-Flavor Herb Tea: A multi-center observational study in Shanghai, China. J Integr Med. 2023; 21(4):369-376.

A synthetic transcription platform for programmable gene expression in mammalian cells.

Precise, scalable, and sustainable control of genetic and cellular activities in mammalian cells is key to developing precision therapeutics and smart biomanufacturing. Here we create a highly tunable, modular, versatile CRISPR-based synthetic transcription system for the programmable control of gene expression and cellular phenotypes in mammalian cells. Genetic circuits consisting of well-characterized libraries of guide RNAs, binding motifs of synthetic operators, transcriptional activators, and additional genetic regulatory elements express mammalian genes in a highly predictable and tunable manner. We demonstrate the programmable control of reporter genes episomally and chromosomally, with up to 25-fold more activity than seen with the EF1α promoter, in multiple cell types. We use these circuits to program the secretion of human monoclonal antibodies and to control T-cell effector function marked by interferon-γ production. Antibody titers and interferon-γ concentrations significantly correlate with synthetic promoter strengths, providing a platform for programming gene expression and cellular function in diverse applications.

Tuning Surface Plasmonic Resonance and Surface Wettability of Au/CrN Films Using Nitrogen-Containing Gas.

The surface plasmonic resonance, surface wettability, and related mechanical nanohardness and of face-centered-cubic (fcc) chromium nitride (CrN) films have been successfully manipulated via the simple method of tuning nitrogen-containing gas with different nitrogen-to-argon ratios, varying from 3.5 (N35), to 4.0 (N40), to 4.5 (N45), which is directly proportional to argon. All of the obtained CrN films showed that the surface wettability was due to hydrophilicity. All of the characteristics were mainly confirmed and explained by using X-ray diffraction (XRD) patterns, including plan-view and cross-section SEM images, with calculations of the average grain size performed via histograms accompanied by different preferred grain orientations. In the present work, not only the surface plasmonic resonance, but also the surface wettability and the related mechanical nanohardness of CrN films were found to be tunable via a simple method of introducing adjustable nitrogen-reactive-containing gas during the deposition process, while the authors suggest that the crystal orientation transition from the (111) to the (200) crystalline plane changed significantly with the nitrogen-containing gas. So the transition of the preferred orientation of CrN's cubic close-packed from (111) to (200) varied at this composite, caused and found by the nitrogen-containing gas, which can be tuned by the nitrogen-to-argon ratio. The surface plasmonic resonance and photoluminescence quenching effects were coupled photon and electron oscillations, which could be observed, and which existed at the interface between the CrN and Au metals in the designed heterostructures.

Comparison of Efficacy of 2% Chlorhexidine Gluconate-Alcohol and 10% Povidone-Iodine-Alcohol against Catheter-Related Bloodstream Infections and Bacterial Colonization at Central Venous Catheter Insertion Sites: A Prospective, Single-Center, Open-Label, Crossover Study.

An effective antiseptic agent is an essential component of a central venous catheter (CVC) care bundle, to protect against catheter-related bloodstream infections (CRBSIs). We conducted a trial to compare the incidences of CRBSI and the growth of insertion site flora in patients with CVC using 2% chlorhexidine gluconate−alcohol (CHG) or 10% povidone-iodine−alcohol (PVI) in the CVC care bundle. Patients who were admitted to two medical intensive care units (ICUs) and had CVC placement for >48 h were enrolled. Using a two-way crossover design with two six-month interventions, the ICUs were assigned to use either CHG or PVI in their care bundles. A total of 446 catheters in 390 subjects were enrolled in the study. The detection rate of flora was greater in the PVI group on both day 7 (26.6% versus 6.3%, p < 0.001) and day 14 (43.2% versus 15.8%, p < 0.001). The incidence rate of CRBSI was higher in the PVI group compared to the CHG group (2.15 vs. 0 events per 1000-catheter-days, p = 0.001), although the significance was lost in the multivariate analysis. In conclusion, 2% CHG was superior to 10% PVI in the CVC care bundle in terms of the inhibition of skin flora growth at CVC insertion sites and was potentially associated with lower incidence rates of CRBSI.

Solution-Processed Smooth Copper Thiocyanate Layer with Improved Hole Injection Ability for the Fabrication of Quantum Dot Light-Emitting Diodes.

Copper thiocyanate (CuSCN) has been gradually utilized as the hole injection layer (HIL) within optoelectronic devices, owing to its high transparency in the visible range, moderate hole mobility, and desirable environmental stability. In this research, we demonstrate quantum dot light-emitting diodes (QLEDs) with high brightness and current efficiency by doping 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ) in CuSCN as the HIL. The experimental results indicated a smoother surface of CuSCN upon F4TCNQ doping. The augmentation in hole mobility of CuSCN and carrier injection to reach balanced charge transport in QLEDs were confirmed. A maximum brightness of 169,230 cd m-2 and a current efficiency of 35.1 cd A-1 from the optimized device were received by adding 0.02 wt% of F4TCNQ in CuSCN, revealing promising use in light-emitting applications.

Obesity-related indices and its association with kidney stone disease: a cross-sectional and longitudinal cohort study.

Obesity increases the risk of several diseases, including kidney stone disease (KSD). The study aimed to explore the relationship between KSD and various obesity-related indices. A total of 121,605 participants in the Taiwan Biobank from December 2008 to February 2020 were analyzed. The association between self-reported history of KSD and eight obesity-related indices, including body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), abdominal volume index (AVI), body roundness index (BRI), conicity index, and triglyceride glucose index was examined in cross-sectional analysis; additionally, the risk of developing kidney stones was analyzed in a longitudinal cohort of 25,268 participants without KSD at baseline, which was a subset of the main cohort. Of all participants, 77,904 (64.1%) were female. Overall, 10.7% of males and 4.0% of females had KSD. Multivariate-adjusted logistic regression showed that all obesity-related indices were significantly associated with KSD. During a mean follow-up of 47 months, kidney stones occurred in 642 (2.5%) participants, and after adjusting for confounders, the risk of developing kidney stones was higher in participants with higher BMI, WC, WHtR, WHR, AVI and BRI. BMI, WC, WHtR, WHR, AVI, and BRI were found to be associated with a higher prevalence of kidney stones as well as development of incident kidney stones, which could be used as predictive factors for development of KSD in clinical practice.

Extraperitoneal Robotic Laparo-Endoscopic Single-Site Plus1-Port Radical Prostatectomy Using the da Vinci Single-Site Platform.

Currently, over 80% of radical prostatectomies have been performed with the da Vinci Surgical System. In order to improve the aesthetic outlook and decrease the morbidity of the operation, the new da Vinci Single Port (SP) system was developed in 2018. However, one major problem is the SP system is still not available in most countries. We aim to present our initial experience and show the safety and feasibility of the single-site robotic-assisted radical prostatectomy (LESS-RP) using the da Vinci Single-Site platform. From June 2017 to January 2020, 120 patients with localized prostate cancer (stage T1-T3b) at Kaohsiung Medical University Hospital were included in this study. We describe our technique and report our initial results of LESS-RP using the da Vinci Si robotic system. Preoperative, intraoperative and postoperative patient variables were recorded. Prostate-specific antigen (PSA)-free survival was also analyzed. A total of 120 patients were enrolled in the study. The median age of patients was 68 years (IQR 63-71), with a median body mass index of 25 kg/m2 (IQR 23-27). The median PSA value before operation was 10.7 ng/mL (IQR 7.9-21.1). The median setup time for creat-ing the extraperitoneal space and ports document was 25 min (IQR 18-34). The median robotic console time and operation time were 135 min (IQR 110-161) and 225 min (IQR 197-274), respectively. Median blood loss was 365 mL (IQR 200-600). There were 11 (9.2%) patients who experienced complications (Clavien-Dindo classification Gr II). The me-dian catheter duration was 8 days (IQR 7-9), with a median of 10 days (IQR 7-11) of hospital stay. The PSA free-survival rate was 86% at a median 19 months (IQR 6-28) of follow up. Robotic radical prostatectomy using the da Vinci Single-Site platform system is safe and feasible, with acceptable outcomes.

Clinical features of gingivostomatitis due to primary infection of herpes simplex virus in children.

BACKGROUND: Primary herpetic gingivostomatitis (PHGS) in children, though usually self-limited, might mimic bacterial and enteroviral pharyngitis clinically. We conducted a study to define the clinical features of PHGS in children. METHODS: Between January 2012 and December 2016, 282 inpatients aged less than 19 years with cell culture-confirmed herpes simplex virus (HSV) infection in a medical center were identified from the virologic laboratory logbook. Clinical data were retrospectively collected. RESULTS: Among the 282 inpatients, 185 cases were considered as PHGS and were included for analysis. Fever was present in 99.5%. The mean duration of fever was 5.11 days (±2.24) with the longest being 17 days. Common oral manifestations included oral ulcers (84.3%), which equally resided in the anterior and posterior part of the oral cavity (65.4% vs. 63.2%), gum swelling and/or bleeding (67.6%), and exudate coated tonsils (16.8%). Leukocytosis (WBC count > 15,000/uL3) was noted in 52 patients (28.1%) and a serum C-reactive protein level > 40 mg/L in 55 patients (29.7%). Fixty-five patients (35%) were diagnosed with PHGS on admission and were significantly more likely to have ulcers over the anterior oral cavity (76.1% vs. 26.7%) and gum swelling/bleeding (76.2% vs. 7.5%, p-value all < 0.001) on admission and were significantly less likely to receive antibiotic treatment (16.9 vs. 36.7%, p-value < 0.01) than others. Forty-six patients (25%) undiagnosed as PHGS on discharge were significantly more likely to have exudate coated on the tonsils, to receive antibiotic treatment and significantly less likely to have gum swelling/bleeding and oral ulcers (all p-values < 0.01). CONCLUSIONS: Meticulously identifying specific oral manifestations of gum swelling/bleeding and ulcers over the anterior oral cavity in children can help making the diagnosis of PHGS earlier and subsequently reduce unnecessary prescription of antibiotics.

Effect and Mechanism of Modified Si Junzitang Combined with Heat-sensitive Moxibustion on IL-17, IL-22, IL-1α and Cys-C in Serum and Exhale Breath Condensate of Patients with Chronic Obstructive Pulmonary Disease at Stable Stage / 中国实验方剂学杂志

Objective::To observe the effect and mechanism of modified Si Junzitang combined with heat-sensitive moxibustion on interleukin-17(IL-17), interleukin-22(IL-22), interleukin-1α(IL-1α) and serum cystatin C(Cys-C )in serum and exhale breath condensate(EBC) of patients with chronic obstructive pulmonary disease at stable stage(COPD, Qi deficiency of lung and spleen). Method::Totally 120 cases of COPD(Qi deficiency of lung and spleen) treated in pulmonary department and thermal moxibustion department of Affiliated Hospital of Jiangxi University of traditional Chinese medicine from January 2019 to June 2019 were included and randomly divided into traditional Chinese medicine group, heat-sensitive moxibustion group and control group. The patients in traditional Chinese medicine group were treated with Si Junzitang, the patients in heat-sensitive Moxibustion group were treated with heat-sensitive moxibustion in addition to traditional Chinese medicine group, and the patients in control group were treated with placebo. All of the 3 groups were treated with oxygen and bronchodilator according to the guidelines. All groups received 3 consecutive courses of treatment, 20 days per course. After 3 courses of treatment, the clinical efficacy of the three groups, the forced expiratory volume in one second (FEV1), the forced expiratory volume in the estimated value in one second (FEV1%), the forced vital capacity (FVC), and IL-17, IL-22, IL-1α in serum and exhale breath condensate (EBC) were measured. Result::There were no statistically significant difference in general clinical data, lung function levels (FEV1, FEV1%, FVC), serum and EBC levels of IL-17, IL-22, IL-1α and Cys-C in the first three groups. The total clinical effective rate of traditional Chinese medicine group was better than the control group (P<0.05), the heat-sensitive moxibustion group was better than the traditional Chinese medicine group (P<0.05) and significantly better than the control group (P<0.01). Compared with the patients before treatment, the level of lung function was improved, while IL-17, IL-22, IL-1α and Cys-C in serum and EBC were reduced(P<0.05). The traditional Chinese medicine group was superior to that in the control group (P<0.05), the heat-sensitive moxibustion group was superior to that in the traditional Chinese medicine group (P<0.05) and significantly superior to that in the control group (P<0.01). Conclusion::Modified Si Junzitang combined with heat-sensitive moxibustion has an anti-inflammatory effect on COPD by stimulating bullishness of human body, improving body immunity, inhibiting inflammatory cytokines, reducing levels of inflammation cytokines IL-17, IL-22, IL-1α, and chronic inflammation markers serum Cys-C and inflammatory reaction, increasing the lung capacity, improving ventilation function and pulmonary function, so as to effectively relieve chest tightness asthma and other symptoms in COPD patients, and improve the clinical efficacy.

Enhanced early immune response of leptospiral outer membrane protein LipL32 stimulated by narrow band mid-infrared exposure.

Previous studies revealed significant impact on cancer cell by mid-infrared (MIR) radiation. However, the effects of narrow band MIR on immune reaction and infectious disease are still unknown. In this study, an enhanced innate immune response was observed through the interaction between Leptospiral outer membrane protein (LipL32) and toll-like receptor 2 (TLR2). Thereafter, human kidney proximal tubular cells (HK-2 cells) initiated a serial reaction of enhanced MCP-1 production. The 6 µm narrow bandwidth light source emitted by waveguide thermal emitter (WTE) was applied to induce carbonyl group (CO bond) stretching vibration during the stage of antigen-receptor complex formation. The amount of MCP-1 gene expression had 2.5 folds increase after narrow band MIR illumination comparing to non-MIR illumination at low dose LipL32 condition. Besides, both ELISA and confocal microscopy results also revealed that the chemokine concentration increased significantly after narrow band MIR illumination either at low or high concentration of LipL32. Furthermore, a specific phenomenon that narrow band MIR can amplify the signal of weak immune response by enhancing sensitivity of the interaction between antigen and receptor was observed. This study exhibits clear evidence that the narrow band MIR exposure can modulate the early immune response of infectious disease and play a potential role to develop host-directed therapy in the future.

A high-throughput screening and computation platform for identifying synthetic promoters with enhanced cell-state specificity (SPECS).

Cell state-specific promoters constitute essential tools for basic research and biotechnology because they activate gene expression only under certain biological conditions. Synthetic Promoters with Enhanced Cell-State Specificity (SPECS) can be superior to native ones, but the design of such promoters is challenging and frequently requires gene regulation or transcriptome knowledge that is not readily available. Here, to overcome this challenge, we use a next-generation sequencing approach combined with machine learning to screen a synthetic promoter library with 6107 designs for high-performance SPECS for potentially any cell state. We demonstrate the identification of multiple SPECS that exhibit distinct spatiotemporal activity during the programmed differentiation of induced pluripotent stem cells (iPSCs), as well as SPECS for breast cancer and glioblastoma stem-like cells. We anticipate that this approach could be used to create SPECS for gene therapies that are activated in specific cell states, as well as to study natural transcriptional regulatory networks.