Design of a water-soluble transmembrane receptor kinase with intact molecular function by QTY code.

Membrane proteins are critical to biological processes and central to life sciences and modern medicine. However, membrane proteins are notoriously challenging to study, mainly owing to difficulties dictated by their highly hydrophobic nature. Previously, we reported QTY code, which is a simple method for designing water-soluble membrane proteins. Here, we apply QTY code to a transmembrane receptor, histidine kinase CpxA, to render it completely water-soluble. The designed CpxAQTY exhibits expected biophysical properties and highly preserved native molecular function, including the activities of (i) autokinase, (ii) phosphotransferase, (iii) phosphatase, and (iv) signaling receptor, involving a water-solubilized transmembrane domain. We probe the principles underlying the balance of structural stability and activity in the water-solubilized transmembrane domain. Computational approaches suggest that an extensive and dynamic hydrogen-bond network introduced by QTY code and its flexibility may play an important role. Our successful functional preservation further substantiates the robustness and comprehensiveness of QTY code.

Prophylactic Antibiotics Delivered Via the Respiratory Tract to Reduce Ventilator-Associated Pneumonia: A Systematic Review, Network Meta-Analysis, and Trial Sequential Analysis of Randomized Controlled Trials.

OBJECTIVES: To assess the effects of antibiotics delivered via the respiratory tract in preventing ventilator-associated pneumonia (VAP). DATA SOURCES: We searched PubMed, Scopus, the Cochrane Library, and ClinicalTrials.gov for studies published in English up to October 25, 2023. STUDY SELECTION: Adult patients with mechanical ventilation of over 48 h and receiving inhaled or instilled antibiotics (with control group) to prevent VAP were included. DATA EXTRACTION: Two independent groups screened studies, extracted the data, and assessed the risk of bias. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess the certainty/quality of the evidence. Results of a random-effects model were reported for overall and predefined subgroup meta-analyses. The analysis was primarily conducted on randomized controlled trials, and observational studies were used for sensitivity analyses. DATA SYNTHESIS: Seven RCTs with 1445 patients were included, of which six involving 1283 patients used nebulizers to deliver antibiotics. No obvious risk of bias was found among the included RCTs for the primary outcome. Compared with control group, prophylactic antibiotics delivery via the respiratory tract significantly reduced the risk of VAP (risk ratio [RR], 0.69 [95% CI, 0.53-0.89]), particularly in subgroups where aminoglycosides (RR, 0.67 [0.47-0.97]) or nebulization (RR, 0.64 [0.49-0.83]) were used as opposed to other antibiotics (ceftazidime and colistin) or intratracheal instillation. No significant differences were observed in mortality, mechanical ventilation duration, ICU and hospital length of stay, duration of systemic antibiotics, need for tracheostomy, and adverse events between the two groups. Results were confirmed in sensitivity analyses. CONCLUSIONS: In adult patients with mechanical ventilation for over 48 h, prophylactic antibiotics delivered via the respiratory tract reduced the risk of VAP, particularly for those treated with nebulized aminoglycosides.

Survey of Ventilator Waveform Interpretation Among ICU Professionals.

BACKGROUND: The interpretation of ventilator waveforms is essential for effective and safe mechanical ventilation but requires specialized training and expertise. This study aimed to investigate the ability of ICU professionals to interpret ventilator waveforms, identify areas requiring further education and training, and explore the factors influencing their interpretation skills. METHODS: We conducted an international online anonymous survey of ICU professionals (physicians, nurses, and respiratory therapists [RTs]), with ≥ 1 y of experience working in the ICU. The survey consisted of demographic information and 15 multiple-choice questions related to ventilator waveforms. Results were compared between professions using descriptive statistics, and logistic regression (expressed as odds ratios [ORs; 95% CI]) was performed to identify factors associated with high performance, which was defined by a threshold of 60% correct answers. RESULTS: A total of 1,832 professionals from 31 countries or regions completed the survey; 53% of respondents answered ≥ 60% of the questions correctly. The 3 questions with the most correct responses were related to waveforms that demonstrated condensation (90%), pressure overshoot (79%), and bronchospasm (75%). Conversely, the 3 questions with the fewest correct responses were waveforms that demonstrated early cycle leading to double trigger (43%), severe under assistance (flow starvation) (37%), and early/reverse trigger (31%). Factors significantly associated with ≥ 60% correct answers included years of ICU working experience (≥ 10 y, OR 1.6 [1.2-2.0], P < .001), profession (RT, OR 2.8 [2.1-3.7], P < .001), highest degree earned (graduate, OR 1.7 [1.3-2.2], P < .001), workplace (teaching hospital, OR 1.4 [1.1-1.7], P = .008), and prior ventilator waveforms training (OR 1.7 [1.3-2.2], P < .001). CONCLUSIONS: Slightly over half respondents correctly identified ≥ 60% of waveforms demonstrating patient-ventilator discordance. High performance was associated with ≥ 10 years of ICU working experience, RT profession, graduate degree, working in a teaching hospital, and prior ventilator waveforms training. Some discordances were poorly recognized across all groups of surveyed professionals.

Molecular Identification and Genetic Characterization of Public Health Threatening Ticks - Chongming Island, China, 2021-2022.

What is already known about this topic?: Although ticks and tick-borne diseases are prevalent throughout China, there remains a knowledge gap regarding their biology and potential risk of distribution to human and animal populations on Chongming Island. The island, being China's third largest and a crucial component in the ecological preservation of the Yangtze Delta region, has yet to be comprehensively studied in this context. What is added by this report?: In this study, employing molecular methodologies, a significant prevalence of Haemaphysalis (H.) longicornis and H. flava ticks - widely recognized for their high pathogenicity - is reported from Chongming Island. Additionally, the identification of two previously unreported species on the island, namely, H. doenitzi and H. japonica, expands our understanding of both the range and evolution of tick species. What are the implications for public health practice?: The populations of humans and animals in nearly all 18 towns on Chongming Island are potentially at risk for transmission of tick-borne infectious agents. As a result, there is a pressing necessity for public health alerts, proactive tick surveillance, and effective screening of suspected clinical cases of tick-borne diseases within the Chongming population.

Synergistic Effects of Rotavirus and Co-Infecting Viral Enteric Pathogens on Diarrheal Disease - Guangzhou City, Guangdong Province, China, 2019.

What is already known about this topic?: Diarrhea represents a substantial public health issue, contributing globally to a high number of pediatric medical consultations, hospital admissions, and mortality rates. What is added by this report?: An increase in diarrheal frequency serves as a critical benchmark for evaluating severity. The predominant pathogens associated with pediatric diarrhea are rotavirus and norovirus, with co-infections exerting a notable compounding effect that leads to more severe diarrhea. What are the implications for public health practice?: Implementing sensitive diagnostic techniques and comprehensive monitoring is paramount in identifying co-infections. Such strategies can provide physicians with critical insights into disease progression, thus considerably reducing the burden of diarrhea.

Aerosol therapy in adult critically ill patients: a consensus statement regarding aerosol administration strategies during various modes of respiratory support.

BACKGROUND: Clinical practice of aerosol delivery in conjunction with respiratory support devices for critically ill adult patients remains a topic of controversy due to the complexity of the clinical scenarios and limited clinical evidence. OBJECTIVES: To reach a consensus for guiding the clinical practice of aerosol delivery in patients receiving respiratory support (invasive and noninvasive) and identifying areas for future research. METHODS: A modified Delphi method was adopted to achieve a consensus on technical aspects of aerosol delivery for adult critically ill patients receiving various forms of respiratory support, including mechanical ventilation, noninvasive ventilation, and high-flow nasal cannula. A thorough search and review of the literature were conducted, and 17 international participants with considerable research involvement and publications on aerosol therapy, comprised a multi-professional panel that evaluated the evidence, reviewed, revised, and voted on recommendations to establish this consensus. RESULTS: We present a comprehensive document with 20 statements, reviewing the evidence, efficacy, and safety of delivering inhaled agents to adults needing respiratory support, and providing guidance for healthcare workers. Most recommendations were based on in-vitro or experimental studies (low-level evidence), emphasizing the need for randomized clinical trials. The panel reached a consensus after 3 rounds anonymous questionnaires and 2 online meetings. CONCLUSIONS: We offer a multinational expert consensus that provides guidance on the optimal aerosol delivery techniques for patients receiving respiratory support in various real-world clinical scenarios.

Optimal Decisions in a Multi-Party Closed-Loop Supply Chain Considering Green Marketing and Carbon Tax Policy.

Global warming and e-waste pollution are two major environmental pollution issues that have attracted widespread attention. The government has adopted various measures to reduce carbon emissions from businesses and to make manufacturers responsible for recycling e-waste. In the face of external pressures, more and more companies are implementing sustainable closed-loop supply chain (CLSC) management to reduce environmental pollution and achieve sustainable development. Therefore, it is essential to study the operational decisions of CLSC enterprises. This paper considers a sustainable CLSC consisting of two competing manufacturers and a dominant retailer. The government imposes a carbon tax on the retailer, and two manufacturers collect used products directly from their customers. We separately examine whether implementing green marketing by the retailer and the collaboration between the two manufacturers can improve their profits. By building decentralized CLSC mathematical models and applying game theory methods, we obtain that green marketing can increase profits for all CLSC members and improve return rates. The collaboration may yield higher total profits for two manufacturers than a decentralized solution, while the retailer's profits may be lost under certain conditions. Finally, we perform several numerical analyses to find the relationship between unit carbon emission tax and social welfare and gain some managerial insights. The study gives key factors that CLSC companies should consider when making decisions to help them achieve sustainability and provides recommendations for the government to set a reasonable unit carbon tax.

The Use of Aerosolized Medications in Adult Intensive Care Unit Patients: A Prospective, Multicenter, Observational, Cohort Study.

Background: Only limited data are available on the real-life clinical utilization of aerosolized medications in intensive care unit (ICU) patients. Exploring the utilization of aerosolized medications in the ICU may contribute to develop appropriate education and improve the quality of aerosol therapy. Methods: A 2-week, prospective, multicenter, observational, cohort study was conducted to record how the aerosolized medications were utilized in the Chinese ICUs, including indications, medications used in solo or combination, dosage, and side-effects in adult patients. Results: A total of 1006 patients from 28 ICUs were enrolled, of which 389 (38.7%) received aerosol therapy. The most common indications for aerosol therapy were difficulty in secretion management (23.1%) and chronic obstructive pulmonary disease exacerbation (18.5%). The combination of inhaled corticosteroids and short-acting muscarinic antagonist was the most commonly used medication (19.5%, 76/389). Ninety-two percent (358/389) of the patients did not have any side effects during aerosol therapy. More patients in the group with mechanical ventilation received bronchodilators than spontaneous breathing patients (81.3% vs. 55.5%, p < 0.001), and more patients who breathed spontaneously through a tracheostomy received mucus-regulating agents than other patients (70% vs. 37.9%, p = 0.004). Conclusion: In mainland China, more than one-third of adult ICU patients received aerosol therapy. Medications utilized during aerosol therapy were variable in patients with different respiratory support. To promote appropriate use of aerosolized medications, high-quality randomized, controlled trials and clinical guidance on aerosolized medication indications and dosing are needed to improve clinical outcomes.

The utilization of aerosol therapy in mechanical ventilation patients: a prospective multicenter observational cohort study and a review of the current evidence.

BACKGROUND: Aerosol delivery via mechanical ventilation has been reported to vary significantly among different intensive care units (ICU). The optimal technique for using each aerosol generator may need to be updated with the available evidence. METHODS: A 2-week prospective multicenter observational cohort study was implemented to record aerosol delivery for mechanically ventilated adult patients in Chinese ICUs. Our data included the type of aerosol device and its placement, ventilator type, humidification, and aerosolized medication administered. A guide for the optimal technique for aerosol delivery during mechanical ventilation was summarized after a thorough literature review. RESULTS: A total of 160 patients (105 males) from 28 ICUs were enrolled, of whom 125 (78.1%) received aerosol therapy via invasive ventilation. Among these 125 patients, 53 received ventilator-integrated jet nebulizer, with 64% (34/53) of them placed the nebulizer close to Y piece in the inspiratory limb. Further, 56 patients used continuous nebulizers, with 84% (47/56) of them placed the nebulizer close to the Y piece in the inspiratory limb. Of the 35 patients who received aerosol therapy via noninvasive ventilation, 30 received single limb ventilators and continuous nebulizers, with 70% (21/30) of them placed between the mask and exhalation port. Only 36% (58/160) of the patients received aerosol treatments consistent with optimal practice. CONCLUSIONS: Aerosol delivery via mechanical ventilation varied between ICUs, and only 36% of the patients received aerosol treatments consistent with optimal practice. ICU clinicians should be educated on the best practices for aerosol therapy, and quality improvement projects aim to improve the quality and outcome of patients with the optimal technique for aerosol delivery during mechanical ventilation are warranted.

One-step generation of composite soybean plants with transgenic roots by Agrobacterium rhizogenes-mediated transformation.

BACKGROUND: Agrobacterium rhizogenes-mediated (ARM) transformation is a highly efficient technique for generating composite plants composed of transgenic roots and wild-type shoot, providing a powerful tool for studying root biology. The ARM transformation has been established in many plant species, including soybean. However, traditional transformation of soybean, transformation efficiency is low. Additionally, the hairy roots were induced in a medium, and then the generated composite plants were transplanted into another medium for growth. This two-step operation is not only time-consuming, but aggravates contamination risk in the study of plant-microbe interactions. RESULTS: Here, we report a one-step ARM transformation method with higher transformation efficiency for generating composite soybean plants. Both the induction of hairy roots and continuous growth of the composite plants were conducted in a single growth medium. The primary root of a 7-day-old seedling was decapitated with a slanted cut, the residual hypocotyl (maintained 0.7-1 cm apical portion) was inoculated with A. rhizogenes harboring the gene construct of interest. Subsequently, the infected seedling was planted into a pot with wet sterile vermiculite. Almost 100% of the infected seedlings could produce transgenic positive roots 16 days post-inoculation in 7 tested genotypes. Importantly, the transgenic hairy roots in each composite plant are about three times more than those of the traditional ARM transformation, indicating that the one-step method is simpler in operation and higher efficiency in transformation. The reliability of the one-step method was verified by CRISPR/Cas9 system to knockout the soybean Rfg1, which restricts nodulation in Williams 82 (Nod-) by Sinorhizobium fredii USDA193. Furthermore, we applied this method to analyze the function of Arabidopsis YAO promoter in soybean. The activity of YAO promoter was detected in whole roots and stronger in the root tips. We also extended the protocol to tomato. CONCLUSIONS: We established a one-step ARM transformation method, which is more convenient in operation and higher efficiency (almost 100%) in transformation for generating composite soybean plants. This method has been validated in promoter functional analysis and rhizobia-legume interactions. We anticipate a broad application of this method to analyze root-related events in tomato and other plant species besides soybean.

Visceral Leishmaniasis - China, 2015-2019.

WHAT IS ALREADY KNOWN ABOUT THIS TOPIC?: Visceral leishmaniasis (VL) is an important vector-borne disease in rural areas of western China. The spreading of VL made its prevention and control become more complicated. WHAT IS ADDED BY THIS REPORT?: The number of VL cases decreased from 2015 (n=498) to 2019 (n=166). However, the mountain-type zoonotic visceral leishmaniasis (MT-ZVL) cases increased from 2015 (n=82, 16.5%) to 2019 (n=122, 73.5%). In addition, both number and proportion of imported cases increased from 2015 (n=18, 3.6%) to 2019 (n=41, 24.7%). The re-emergence of MT-ZVL was considerable; 13 historically-endemic counties reported 48 indigenous cases. Infants and young children were the high risk population of VL (848, 62.4%) followed by farmers (303, 22.3%). WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: Both MT-ZVL and imported cases showed an increasing trend in China. Therefore, two actions are needed to control VL: 1) to prevent re-emergence and spreading of MT-ZVL; and 2) to ensure timely diagnosis and appropriate treatment to avoid fatal VL cases, especially in non-endemic areas.

Identification of a novel mutation of the NTRK1 gene in patients with congenital insensitivity to pain with anhidrosis (CIPA).

INTRODUCTION: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive disorder resulting from NTRK1 mutation. Over 105 NTRK1 mutations have been reported in CIPA patients worldwide. The causative NTRK1 mutations lead to loss of function of the TrkA protein, an important ligand for nerve growth factor (NGF), and therefore induce various clinical phenotypes associated with neuron maturation defects. MATERIALS AND METHODS: Three patients from unrelated families with CIPA were subjected to detailed clinical examinations. Blood samples were collected from all the patients and their available family members, as well as 200 healthy volunteers. Sanger sequencing for all the exons and splicing sites of NTRK1 was performed on all samples. The phenotype-genotype relationship and genetic epidemiology of Chinese CIPA patients were also analysed. RESULTS: A total of four different NTRK1 mutations [c.851-33T>A, c.44G>A (p.Trp15*), c.287+2dupT, c.1549G>C (p.Gly517Arg)] were identified in these families, and c.1549G>C (p.Gly517Arg) was a novel mutation that had not been reported previously. The 'mild' manifestations observed in patients with c.851-33T>A indicated this mutation as a 'mild' mutation. After reviewing studies reporting mutations in Chinese CIPA patients, we speculate the mutation c.851-33T>A is one of the founder mutations in the Chinese population. CONCLUSIONS: Our research expanded the spectrum of the NTRK1 mutations associated with CIPA patients, provided additional clues relating to the phenotype-genotype relationship in CIPA, and summarized the features of the genetic epidemiology of CIPA in the Chinese ethnic group.

High-flow nasal cannula oxygen therapy is superior to conventional oxygen therapy but not to noninvasive mechanical ventilation on intubation rate: a systematic review and meta-analysis.

BACKGROUND: High-flow nasal cannula oxygen (HFNC) is a relatively new therapy used in adults with respiratory failure. Whether it is superior to conventional oxygen therapy (COT) or to noninvasive mechanical ventilation (NIV) remains unclear. The aim of the present study was to investigate whether HFNC was superior to either COT or NIV in adult acute respiratory failure patients. METHODS: A review of the literature was conducted from the electronic databases from inception up to 20 October 2016. Only randomized clinical trials comparing HFNC with COT or HFNC with NIV were included. The intubation rate was the primary outcome; secondary outcomes included the mechanical ventilation rate, the rate of escalation of respiratory support and mortality. RESULTS: Eleven studies that enrolled 3459 patients (HFNC, n = 1681) were included. There were eight studies comparing HFNC with COT, two comparing HFNC with NIV, and one comparing all three. HFNC was associated with a significant reduction in intubation rate (OR 0.52, 95% CI 0.34 to 0.79, P = 0.002), mechanical ventilation rate (OR 0.56, 95% CI 0.33 to 0.97, P = 0.04) and the rate of escalation of respiratory support (OR 0.45, 95% CI 0.31 to 0.67, P < 0.0001) when compared to COT. There was no difference in mortality between HFNC and COT utilization (OR 1.01, 95% CI 0.67 to 1.53, P = 0.96). When HFNC was compared to NIV, there was no difference in the intubation rate (OR 0.96; 95% CI 0.66 to 1.39, P = 0.84), the rate of escalation of respiratory support (OR 1.00, 95% CI 0.77 to 1.28, P = 0.97) or mortality (OR 0.85, 95% CI 0.43 to 1.68, P = 0.65). CONCLUSIONS: Compared to COT, HFNC reduced the rate of intubation, mechanical ventilation and the escalation of respiratory support. When compared to NIV, HFNC showed no better outcomes. Large-scale randomized controlled trials are necessary to prove our findings. TRIAL REGISTRATION: PROSPERO International prospective register of systematic reviews on May 25, 2016 registration no. CRD42016039581 .

Bioengineered Plants Can Be a Useful Source of Omega-3 Fatty Acids.

Omega-3 fatty acids have proven to be very essential for human health due to their multiple health benefits. These essential fatty acids (EFAs) need to be uptaken through diet because they are unable to be produced by the human body. These are important for skin and hair growth as well as for proper visual, neural, and reproductive functions of the body. These fatty acids are proven to be extremely vital for normal tissue development during pregnancy and infancy. Omega-3 fatty acids can be obtained mainly from two dietary sources: marine and plant oils. Eicosapentaenoic acid (EPA; C20:5 n-3) and docosahexaenoic acid (DHA; C22:6 n-3) are the primary marine-derived omega-3 fatty acids. Marine fishes are high in omega-3 fatty acids, yet high consumption of those fishes will cause a shortage of fish stocks existing naturally in the oceans. An alternative source to achieve the recommended daily intake of EFAs is the demand of today. In this review article, an attempt has, therefore, been made to discuss the importance of omega-3 fatty acids and the recent developments in order to produce these fatty acids by the genetic modifications of the plants.

Genome-wide analysis of auxin transport genes identifies the hormone responsive patterns associated with leafy head formation in Chinese cabbage.

Auxin resistant 1/like aux1 (AUX/LAX), pin-formed (PIN) and ATP binding cassette subfamily B (ABCB/MDR/PGP) are three families of auxin transport genes. The development-related functions of the influx and efflux carriers have been well studied and characterized in model plants. However, there is scant information regarding the functions of auxin genes in Chinese cabbage and the responses of exogenous polar auxin transport inhibitors (PATIs). We conducted a whole-genome annotation and a bioinformatics analysis of BrAUX/LAX, BrPIN, and BrPGP genes in Chinese cabbage. By analyzing the expression patterns at several developmental stages in the formation of heading leaves, we found that most auxin-associate genes were expressed throughout the entire process of leafy head formation, suggesting that these genes played important roles in the development of heads. UPLC was used to detect the distinct and uneven distribution of auxin in various segments of the leafy head and in response to PATI treatment, indicated that the formation of the leafy head depends on polar auxin transport and the uneven distribution of auxin in leaves. This study provides new insight into auxin polar transporters and the possible roles of the BrLAX, BrPIN and BrPGP genes in leafy head formation in Chinese cabbage.

Transcriptomic and proteomic analyses provide new insights into the regulation mechanism of low-temperature-induced leafy head formation in Chinese cabbage.

UNLABELLED: In Chinese cabbage, leafy head-related traits are directly related to the cabbage yield and marketability, which are often primarily concerned target for breeders. Although intensive studies has been on head formation in Chinese cabbage in the past decade, very scanty information is available on mechanism involved in the head formation under the influence of low temperature at transcriptome and proteome perspective. In this study, quantitative expression profiling based on RNA-Seq transcriptome and iTRAQ proteome were combined to investigate this trait for a global picture of the molecular dynamics. Total of 2931 transcripts and 365 proteins were identified with significantly changed level in abundance from heading and non-heading Chinese cabbage. Related analyses including function annotations, hierarchical categories, as well as the correlation from transcript-to-proteins were performed. The results indicated that the leafy head formation of Chinese cabbage has involved a complex regulatory pattern. The correlated genes that were mapped to the pathway of plant hormone signal transduction suggested that the head formation might be an integrated result of various plant hormones. Our combined analysis will provide a comprehensive approach to understanding the regulation mechanism of leafy head formation in Chinese cabbage. BIOLOGICAL SIGNIFICANCE: This study revealed the direct relation of leafy-heading traits with the yield of the plant. A comprehensive investigation was done by integrating quantitative expression profiling analysis of transcriptome and proteomic to provide crucial information for further research on the molecular mechanism involved in head formation in Chinese cabbage. The correlation of transcript-to-protein in abundance may afford some necessary information of involvement of post-transcriptional factors influencing leafy head formation in Chinese cabbage.

[The application of actively heated humidified high flow nasal cannula oxygen therapy in adults].

OBJECTIVE: Actively heated, humidified high flow nasal cannula oxygen therapy (HFNC) is a new type of oxygen therapy. Because of its unique physiological effects, the clinical application is becoming more and more popular. This article is to summarize the physiological effects, clinical application and short comings of HFNC. Compared with conventional oxygen therapy, HFNC helps to improve oxygenation better, and it is more comfortable than non-invasive ventilation (NIV) in use. Proper use of HFNC may be able to reduce the use of NIV and decrease the rate of endotracheal intubation. It can be used for adults with mild to moderate hypoxia, or for patients undergoing palliative care. However, the experience of the use of HFNC in adults is limited, and there is yet no corresponding clinical guideline. Therefore, further research with a large sample is required to determine the long-term effect of this technique, and to identify the adult patient population to whom is most beneficial.