Coreactant-Free Zirconium Metal-Organic Framework with Dual Emission for Ratiometric Electrochemiluminescence Detection of HIV DNA.

Owing to the limitations of dual-signal luminescent materials and coreactants, constructing a ratiometric electrochemiluminescence (ECL) biosensor based on a single luminophore is a huge challenge. This work developed an excellent zirconium metal-organic framework (MOF) Zr-TBAPY as a single ECL luminophore, which simultaneously exhibited cathodic and anodic ECL without any additional coreactants. First, Zr-TBAPY was successfully prepared by a solvothermal method with 1,3,6,8-tetra(4-carboxyphenyl)pyrene (TBAPY) as the organic ligand and Zr4+ cluster as the metal node. The exploration of ECL mechanisms confirmed that the cathodic ECL of Zr-TBAPY originated from the pathway of reactive oxygen species (ROS) as the cathodic coreactant, which is generated by dissolved oxygen (O2), while the anodic ECL stemmed from the pathway of generated Zr-TBAPY radical itself as the anodic coreactant. Besides, N,N-diethylethylenediamine (DEDA) was developed as a regulator to ECL signals, which quenched the cathodic ECL and enhanced the anodic ECL, and the specific mechanisms of its dual action were also investigated. DEDA can act as the anodic coreactant while consuming the cathodic coreactant ROS. Therefore, the coreactant-free ratiometric ECL biosensor was skillfully constructed by combining the regulatory role of DEDA with the signal amplification reaction of catalytic hairpin assembly (CHA). The ECL biosensor realized the ultrasensitive ratio detection of HIV DNA. The linear range was 1 fM to 100 pM, and the limit of detection (LOD) was as low as 550 aM. The outstanding characteristic of Zr-TBAPY provided new thoughts for the development of ECL materials and developed a new way of fabricating the coreactant-free and single-luminophore ratiometric ECL platform.

Knowledge, Attitudes, and Practices about Hyperuricemia and Gout in Community Health Workers and Patients with Diabetes.

Hyperuricemia exhibits a high incidence among individuals with diabetes; however, the significance of hyperuricemia and gout is often underestimated. This study aimed to assess the knowledge, attitude, and practice of hyperuricemia and gout among community health workers and patients with diabetes. Two questionnaires were designed to investigate knowledge, attitudes, and practices of hyperuricemia and gout among community health workers and patients with diabetes in Chenghua District, Chengdu, from August 2021 to January 2022. A total of 709 community health workers were included, whose average score was 17.74/30. Approximately half of general practitioners (GPs) demonstrated knowledge regarding the target serum uric acid levels for hyperuricemia and gout. Only 11.2% of GPs were fully aware of the preferred medicine for acute gout. The majority of GPs (86.7%) demonstrated limited awareness regarding the contraindications associated with colchicine, while a significant proportion (65.1%) lacked knowledge about the specific classes of drugs that inhibit uric acid synthesis. Among the 508 patients with diabetes included in this survey, 32.3% demonstrated awareness of hyperuricemia, while 60.8% exhibited knowledge regarding gout. The average score attained by these individuals was recorded at 7.21 out of a total of 26 points. The majority of patients with diabetes (87.8%) held the mistaken belief that hyperuricemia definitely led to the development of gout. Almost 66% agreed that a massage or a hot compress could be used when acute gouty arthritis attacks. The knowledge rate of hyperuricemia and gout among community health workers was moderate, while it was low in patients with diabetes.

Related factors to illness perception of individuals with diabetic foot ulcers: A structural equation modelling test.

BACKGROUND: Diabetic foot is a common and severe complication of diabetes with limited movement, emotional distress, and poor quality of life. Illness perception was introduced to improve patients' psychological status and quality of life with diabetic foot ulcers. The aim of the study is to explore the related factors of illness perception, and to structure an illness perception model of patients with diabetic foot ulcers. METHODS: We recruited 208 patients with diabetic foot ulcers from six hospitals from April 2021 to February 2022. A multicentered cross-sectional study was conducted to collect the data. Questionnaires included illness perception, coping behavior, emotional status, and quality of life. We performed multiple linear regression analysis with illness perception as the dependent variable, and evaluated the goodness of fit of the resulting structural equations models based on covariance structural analysis. RESULTS: Illness perception was negatively related to coping behavior and quality of life, and it was positively correlated with yield-coping behavior, anxiety, and depression. The pain, diabetes duration, quality of life, yield-coping strategy, and sex were the factors that affected illness perception in patients with DFUs (P＜0.05). The resulting model was found to exhibit goodness of fit. CONCLUSION: Illness perception had an especially strong and direct impact on quality of life, depression, and anxiety. Therefore, it is significant to improve illness perception in patients with DFUs, and provide positive support based on cognitive behavioral therapy to improve illness perception, quality of life, and emotional status.

Kinesitherapy for Knee Osteoarthritis Patients Physical and Psychological Health Based on "Traditional Chinese Exercise" Management Modalities: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Traditional Chinese exercise ("TCE" management modalities), including but not limited to Tai Chi, Baduanjin, and Yijinjing, has a good effect on improving the physical function of patients with knee osteoarthritis, but less attention has been paid to the impact on the psychological health of patients, and currently there is insufficient evidence to support it. We conducted this study to provide a systematic synthesis of best evidence regarding the physical and mental health of patients with knee osteoarthritis treated by traditional Chinese exercise. Literature on the effectiveness of traditional Chinese exercise (Tai Chi, Baduanjin, Yijinjing, Qigong, etc.) versus conventional therapy (muscle-strength training of the lower extremity and aerobic training, wellness education, quadriceps strengthening exercises, etc.) on Western Ontario and McMaster Universities Arthritis Index (WOMAC), visual analog scale (VAS), Short Form-36 (SF-36), Timed Up and Go Test (TUG), and Berg Balance Scale (BBS) in knee osteoarthritis (KOA) from Pubmed, Web of Science, Ovid Technologies, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), Wanfang Database, and SinoMed were collected from their inception to April 2022. Thirty-three studies with 2621 cases were included in this study. The study's results indicated that compared with conventional therapy, traditional Chinese exercise had more advantages on patients' WOMAC score, significantly reducing patients' overall WOMAC score (SMD = -0.99; 95% CI: -1.38, -0.60; p < 0.00001) and relieving pain (SMD = -0.76; 95% CI: -1.11, -0.40; p < 0.0001) in patients with KOA. It also has advantages over conventional therapy in improving mental component score (MCS) (SMD = 0.32; 95% CI: -0.00, 0.65; p = 0.05) and physical component score (PCS) (SMD = 0.34; 95% CI: 0.05, 0.62; p = 0.02). Compared with conventional therapy, traditional Chinese exercise can significantly reduce the effect on timed up and go test (TUG) score (SMD = -0.30; 95% CI: -0.50, -0.11; p = 0.002), beck depression inventory (DBI) score (SMD = -0.62; 95% CI: -1.03, -0.22; p = 0.002), and increase the impact on Berg Balance Scale (BBS) score (SMD = 0.60; 95% CI: 0.37, 0.83; p < 0.00001). The findings of this study indicated that traditional Chinese exercise improved body function and mental health in patients with knee osteoarthritis significantly. More high-quality clinical evidence-based data was needed to confirm the therapeutic effect of traditional Chinese exercise on the physical and mental health in KOA patients.

Ratiometric Electrochemiluminescence of Zirconium Metal-Organic Framework as a Single Luminophore for Sensitive Detection of HPV-16 DNA.

This study developed a new zirconium metal-organic framework (MOF) luminophore named Zr-DPA@TCPP with dual-emission electrochemiluminescence (ECL) characteristics at a resolved potential. First, Zr-DPA@TCPP with a core-shell structure was effectively synthesized through the self-assembly of 9,10-di(p-carboxyphenyl)anthracene (DPA) and 5,10,15,20-tetra(4-carboxyphenyl)porphyrin (TCPP) as the respective organic ligands and the Zr cluster as the metal node. The reasonable integration of the two organic ligands DPA and TCPP with ECL properties into a single monomer, Zr-DPA@TCPP, successfully exhibited synchronous anodic and cathodic ECL signals. Besides, due to the impressively unique property of ferrocene (Fc), which can quench the anodic ECL but cannot affect the cathodic ECL signal, the ratiometric ECL biosensor was cleverly designed by using the cathode signal as an internal reference. Thus, combined with DNA recycle amplification reactions, the ECL biosensor realized sensitive ratiometric detection of HPV-16 DNA with the linear range of 1 fM-100 pM and the limit of detection (LOD) of 596 aM. The distinctive dual-emission properties of Zr-DPA@TCPP provided a new idea for the development of ECL luminophores and opened up an innovative avenue of fabricating the ratiometric ECL platform.

Prevalence and associated factors of hyperuricemia among Chinese patients with diabetes: a cross-sectional study.

Background: As a part of metabolic syndrome, hyperuricemia has a higher incidence in patients with diabetes than in the general population owing to various underlying factors. Objectives: The objective of the present study was to investigate the prevalence of hyperuricemia among patients with diabetes and identify associated factors. Design: A cross-sectional study. Methods: Herein, we included patients with diabetes managed at nine healthcare centers in Chenghua District, Chengdu, from February 2021 to November 2021. Clinical data, lifestyle habits, and laboratory data were collected to determine the prevalence and factors associated with hyperuricemia. Results: In total, we included 1577 patients with diabetes (males, 50.35%; females, 49.65%). The median serum uric acid level was 337.9 µmol/L, and the prevalence of hyperuricemia in patients with diabetes was 21.24%. The prevalence of hyperuricemia in male patients was significantly higher than in females (29.35% in males versus 13.03% in females, p < 0.001). Male patients with obesity (p = 0.006) or triglyceride (TG) ⩾ 1.7 mmol/L (p < 0.001) had a high risk of developing hyperuricemia, and hyperuricemia was negatively associated with estimated glomerular filtration rate (eGFR) ⩾ 60 mL/min/1.73 m2 (p < 0.001), glycosylated hemoglobin (HbA1c) ⩾ 7% (p < 0.001), fenofibrate (p = 0.010), and sodium-glucose cotransporter 2 (SGLT-2) inhibitors (p = 0.035). Considering females, overweight (p = 0.004), alanine transaminase (ALT) > 40 U/L (p < 0.001), and TG ⩾ 1.7 mmol/L (p = 0.015) showed a significant positive correlation with hyperuricemia, while eGFR ⩾ 60 mL/min/1.73 m2 (p < 0.001) was negatively associated with the risk of hyperuricemia. Conclusion: Hyperuricemia is highly prevalent in patients with diabetes, especially in males. In addition to traditionally associated factors, fenofibrate and SGLT-2 inhibitors were also associated with the risk of hyperuricemia. Registration: The study protocol was registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn/), and the registration number was ChiCTR 2100042742.

Insight into the role of crystallinity in oxide electrolytes enabling high-performance all-solid-state lithium-sulfur batteries.

All-solid-state lithium-sulfur batteries (ASSLSBs) would be a promising candidate for the next-generation batteries due to the utilization of energy-dense electrodes and the non-flammable oxide solid-state electrolytes (SSEs), but still face great challenges such as low ionic conductivity of SSEs, poor interfacial contact and lithium (Li) dendrite propagation. Herein, we regulated the crystallinity degrees of the large-scale-fabricated Li1.5Al0.5Ge1.5(PO4)3 (LAGP) SSEs and explored the critical role of crystallinity optimization in reinforcing the basic properties of LAGP, developing a fundamental explanation for the inherent relation between the crystallinity and the performance of ASSLSBs. Benefiting from the optimized crystallinity (∼99.9 %), the large-scale-fabricated LAGP not only realizes the low surface roughness and high ionic conductivity (2.11 × 10-4 S cm-1) to improve interfacial contact and reduce resistance in ASSLSBs, but also possesses the dense internal structure with low porosity (1.49 %) to physically resist dendritic propagation and penetration. Consequently, the ASSLSB with the optimized LAGP delivers a high reversible capacity of 647.9 mAh/g even after 150 cycles at 0.1 C. This work confirms the significance of crystallinity in understanding the working mechanisms of oxide SSEs and developing future high-performance ASSLSBs.

Integrating single-cell analysis and machine learning to create glycosylation-based gene signature for prognostic prediction of uveal melanoma.

Background: Increasing evidence suggests a correlation between glycosylation and the onset of cancer. However, the clinical relevance of glycosylation-related genes (GRGs) in uveal melanoma (UM) is yet to be fully understood. This study aimed to shed light on the impact of GRGs on UM prognosis. Methods: To identify the most influential genes in UM, we employed the AUCell and WGCNA algorithms. The GRGs signature was established by integrating bulk RNA-seq and scRNA-seq data. UM patients were separated into two groups based on their risk scores, the GCNS_low and GCNS_high groups, and the differences in clinicopathological correlation, functional enrichment, immune response, mutational burden, and immunotherapy between the two groups were examined. The role of the critical gene AUP1 in UM was validated through in vitro and in vivo experiments. Results: The GRGs signature was comprised of AUP1, HNMT, PARP8, ARC, ALG5, AKAP13, and ISG20. The GCNS was a significant prognostic factor for UM, and high GCNS correlated with poorer outcomes. Patients with high GCNS displayed heightened immune-related characteristics, such as immune cell infiltration and immune scores. In vitro experiments showed that the knockdown of AUP1 led to a drastic reduction in the viability, proliferation, and invasion capability of UM cells. Conclusion: Our gene signature provides an independent predictor of UM patient survival and represents a starting point for further investigation of GRGs in UM. It offers a novel perspective on the clinical diagnosis and treatment of UM.

Urogenital tract and rectal microbiota composition and its influence on reproductive outcomes in infertile patients.

Introduction: Microbiota in the human body are closely related to human diseases. Female urogenital tract and rectal microbes have been considered as important factors affecting female pregnancy, but the mechanism is unknown. Methods: Cervical, vaginal, urethral, and rectal swabs were collected from 22 infertile patients and 10 controls, and follicular fluid was extracted from 22 infertile patients. The microbial composition of different sampling sites of infertile patients was examined. By comparing the microbial composition difference between infertile patients and controls and combining bioinformatics methods to analyze the potential impact of the female urogenital tract (cervical, vaginal and urethral) and rectal microbial diversity on female infertility and pregnancy outcomes. Results: Lactobacillus predominated in the female urogenital tract, but its abundance decreased in infertile patients, whereas the abundance of Gardnerella and Atopobium increased. The microbial changes in the urethra had the same trend as that in the vagina. Compared with healthy controls, the cervical and rectal microbial diversity of infertile patients were significantly increased and decreased, respectively. There might be interactions between microbes in different parts of female. Geobacillus thermogeniticans was enriched in the urogenital tract and rectum of infertile patients, and has a good predictive effect on infertility. Compared with infertile patients, L. johnsonii was enriched in the vagina, urethra, and intestine of the control group. L. acidophilus in follicular fluid might be associated with Non-pregnancy. Conclusion: This study found that the microbial composition of infertile patients was changed compared with that of healthy people. The translocation of Lactobacillus between the rectum and urogenital tract might play a protective barrier role. The changes of Lactobacillus and Geobacillus might be related to female infertility or pregnancy outcome. The study provided a theoretical basis for the future treatment of female infertility from the perspective of microorganisms by detecting the microbial changes associated with female infertility.

Global mortality of diabetic foot ulcer: A systematic review and meta-analysis of observational studies.

AIM: To estimate the long-term mortality and risk factors in patients with diabetic foot ulcer (DFU). METHODS: We systematically searched Medline (PubMed), Embase, Scopus, Web of Science, Cochrane Library, China Science and Technology Journal Database (CQVIP), China National Knowledge Infrastructure, the Chinese Biomedical Literature Database (SinoMed) and Wanfang Data from 1 January 2011 to 31 July 2022. All observational studies that reported long-term mortality of patients with DFU were included. Random effect models were used to pool the reconstructed participant data from Kaplan-Meier curves. The primary outcome was the long-term survival of patients with DFU. An aggregate data meta-analysis was also performed. RESULTS: We identified 34 studies, with 124 376 participants representing 16 countries, among whom there were 51 386 deaths. Of these, 27 studies with 21 171 patients were included in the Kaplan-Meier-based meta-analysis. The estimated Kaplan-Meier-based survival rates were 86.9% (95% confidence interval [CI] 82.6%-91.5%) at 1 year, 66.9% (95% CI 59.3%-75.6%) at 3 years, 50.9% (95% CI 42.0%-61.7%) at 5 years and 23.1% (95% CI 15.2%-34.9%) at 10 years. The results of the aggregate data-based meta-analysis were similar. Cardiovascular disease and infection were the most common causes of death, accounting for 46.6% (95% CI 33.5%-59.7%) and 24.8% (95% CI 16.0%-33.5%), respectively. Patients with older age (per 1 year, hazard ratio [HR] 1.054, 95% CI 1.045-1.063), peripheral artery disease (HR 1.882, 95% CI 1.592-2.225), chronic kidney disease (HR 1.535, 95% CI 1.227-1.919), end-stage renal disease (HR 3.586, 95% CI 1.333-9.643), amputation (HR 2.415, 95% CI 1.323-4.408) and history of cardiovascular disease (HR 1.449, 95% CI 1.276-1.645) had higher mortality risk. CONCLUSIONS: This meta-analysis found that the overall mortality of DFU was high, with nearly 50% mortality within 5 years. Cardiovascular disease and infection were the two leading causes of death.

Mesenchymal stem cell-derived exosomes: The dawn of diabetic wound healing.

Chronic wound healing has long been an unmet medical need in the field of wound repair, with diabetes being one of the major etiologies. Diabetic chronic wounds (DCWs), especially diabetic foot ulcers, are one of the most threatening chronic complications of diabetes. Although the treatment strategies, drugs, and dressings for DCWs have made great progress, they remain ineffective in some patients with refractory wounds. Stem cell-based therapies have achieved specific efficacy in various fields, with mesenchymal stem cells (MSCs) being the most widely used. Although MSCs have achieved good feedback in preclinical studies and clinical trials in the treatment of cutaneous wounds or other situations, the potential safety concerns associated with allogeneic/autologous stem cells and unknown long-term health effects need further attention and supervision. Recent studies have reported that stem cells mainly exert their trauma repair effects through paracrine secretion, and exosomes play an important role in intercellular communication as their main bioactive component. MSC-derived exosomes (MSC-Exos) inherit the powerful inflammation and immune modulation, angiogenesis, cell proliferation and migration promotion, oxidative stress alleviation, collagen remodeling imbalances regulation of their parental cells, and can avoid the potential risks of direct stem cell transplantation to a large extent, thus demonstrating promising performance as novel "cell-free" therapies in chronic wounds. This review aimed to elucidate the potential mechanism and update the progress of MSC-Exos in DCW healing, thereby providing new therapeutic directions for DCWs that are difficult to be cured using conventional therapy.

Hollow urchin-like Mn3O4 microspheres as an advanced sulfur host for enabling Li-S batteries with high gravimetric energy density.

Lithium-sulfur (Li-S) batteries are considered to be promising candidates for next-generation storage systems. However, the practical applications are still hindered by the severe capacity decay, mainly caused by the large volume change, polysulfide shuttle and sluggish sulfur conversion kinetics. Herein, hollow urchin-like Mn3O4 (HU-Mn3O4) microspheres as sulfur hosts have been synthesized by the hydrothermal method and calcination treatment, aiming to prevent the polysulfide dissolution (benefiting from the strong polysulfide anchoring effect of Mn3O4) and alleviate the volume expansion of sulfur (benefiting from the special hollow structure). Meanwhile, the urchin-like thorny surface also facilitates the rapid ion/electron transfer and the abundant active sites for the fast sulfur redox kinetics. When used as the sulfur host in Li-S batteries, the S@HU-Mn3O4 cathode delivers a high initial capacity of 1137.4 mAh g-1 with a slow capacity decay of 0.042% after 200 cycles at 0.2 C. Even under the conditions of lean electrolyte (E/S = 7 mL g-1) and low N/P ratio (N/P = 2.1), the S@HU-Mn3O4 cathode still enables a stable cycling performance with a high gravimetric energy density (202 Wh kg cell-1), demonstrating its great potential in the development of future practical Li-S battery materials.

Efficacy and Safety of Pentoxifylline for Venous Leg Ulcers: An Updated Meta-Analysis.

The venous leg ulcers are debilitating, painful, and often unresponsive to advanced dressing treatments, so drugs used locally and systematically are essential adjuvant therapy-pentoxifylline (PTX) whose anti-inflammatory effects may offer a promising avenue to treat venous leg ulcers. However, the current results are controversial. To further evaluate the efficacy and safety of PTX, we performed an updated meta-analysis of randomized placebo-controlled trials of PTX in the treatment of venous leg ulcers. We systematically searched multiple electronic databases PubMed, Web of Science, Embase, the Cochrane Library, the Cochrane Central Register of Controlled Trials, China Science and Technology Journal Database, WanFang Data, China National Knowledge Infrastructure, and the Chinese Biomedical Literature Database to identify eligible studies. Randomized clinical trials of pentoxifylline versus placebo treatment in patients with venous leg ulcers were considered for inclusion. The primary outcomes included ulcer healing rate and the incidence of adverse events after treatment. The secondary outcomes were the ulcer significant improvement (the ulcer size shrank by more than 60% after treatment) rate, mean duration of complete wound healing and changes in mean ulcer size. A meta-analysis and qualitative analysis were conducted to estimate endpoints. A total of 13 randomized clinical trials, including 921 individuals, were finally included. Compared with placebo, pentoxifylline significantly improved the ulcer healing rate (RR = 1.59, 95%CI 1.22 to 2.07, P < .001) and significant improvement rate (RR = 2.36, 95%CI 1.31 to 4.24, P = .004) while increased the incidence of gastrointestinal disturbances (RR = 2.29, 95%CI 1.04 to 5.03, P = .04) at the same time. Moreover, pentoxifylline also shortened mean duration of complete wound healing (P = .007) and shrank ulcer size (P = .02). Currently available evidence suggests that pentoxifylline could help venous leg ulcers heal more quickly and effectively. However, the evidence is insufficient to prove the results due to moderate-certainty evidence. Large-scale, well-designed randomized clinical trials are warranted.

[A Case of Pseudohypoaldosteronism Type â ¡ (PHA2) Caused by a Novel Mutation of KLHL3].

The patient, a 41-year-old woman, was admitted because "it was found out she had elevated serum potassium levels for 18 days". Eighteen days prior to admission at our hospital, the patient was found to have elevated serum potassium during hospitalization at another hospital, where the patient received symptomatic treatment and was discharged after her serum potassium returned to a normal level. However, the patient still had elevated serum potassium repeatedly and was referred to our hospital for further examination. The patient had a history of acute nephritis and gestational hypertension. Six months prior to admission at our hospital, it was found out that the patient had slightly elevated blood pressure, but no intervention was done. The patient's father has a history of hypertension and diabetes. After admission, laboratory results showed that the patient had hyperkalemia, hyperchloremia and metabolic acidosis. The level of plasma renin was obviously below the normal range, but the concentration of plasma aldosterone was within the normal range. A new mutation locus (c.1115delG) in KLHL3 (Kelch like family member 3) gene was revealed by genetic testing, leading to the diagnosis of pseudoaldosteronism type Ⅱ (PHA2). The patient was given regular treatment of oral hydrochlorothiazide hydrochloride at set intervals. Subsequently, her blood electrolyte level, blood pH, BE and BEB have returned to normal levels. The patient was followed up for 12 months and did not feel unwell during the follow-up period.

How human thermal plume influences near-human transport of respiratory droplets and airborne particles: a review.

With mounting evidence and notable cases of large clustered infections, airborne transmission via droplets and particles has been recently acknowledged as an effective mode of transmission for COVID-19. How droplets and aerosol particles disperse are being transported into the human breathing zone-the last few inches for airborne transmission to effectuate-remains a key question which has been widely overlooked. Human thermal plume refers to the constantly rising airflows around the boundary layer of human body due to persisting temperature gradients between the body surfaces and the ambient air. Ample evidence indicated that the thermal plume controls the dispersion and transport of aerosols in the human microenvironment. Given that in calm indoor environments most air inhaled by human comes from the boundary layer where thermal plume flows through constantly, the role of thermal plume needs to be scrutinized to predict the diffusion of droplets, aerosols and other airborne carriers of the novel coronavirus around the human body for prioritizing infection control strategies. Here, we assessed the potential influences of the thermal plume on the transmission of COVID-19 and other airborne pathogens by reviewing the most pertinent evidence and analyzing key variables in the formation of thermal plume in indoor environments, e.g., ambient temperature, human posture and type of clothing. Our reviewed evidence and data indicate that the human thermal plume should facilitate the airborne transmission of COVID-19 in enclosed spaces by elevating small droplets and airborne particles into the breathing zone from lower regions and ascending respiratory droplets from the sources into the upper atmosphere. By drawing attention to aerosol transport dynamics in the human microenvironment, these insights may be useful for understanding COVID-19 transmission in enclosed spaces, especially those intended for public use.

Open defecation and squat toilets, an overlooked risk of fecal transmission of COVID-19 and other pathogens in developing communities.

The novel coronavirus disease COVID-19 has infected over 46 million people in 219 countries and territories. Following evidence of viral loadings and infectivity of feces of infected individuals, public health authorities have suggested to take precautions on the transmission of COVID-19 via fecal-associated routes. Recent discussions on fecal transmission of COVID-19 have mainly focused on municipal sewage. Yet, a widely neglected aspect in containing the virus is that a major part of the population in developing regions do not have access to private, clean sanitary facilities. Therefore, we hypothesize that open defecation and the prevalent use of squat toilets are additional risk factors in those communities. Here, we review fecal transmission of COVID-19, the practices of open defecation, and the resultant routes of transmission of fecal pathogens. Also, we highlight the open design of common squat toilets and the potential exposure to fecal droplets and residues. We observed that at least 20 countries reporting more than 10,000 confirmed infections have 5-26% of their population practicing open defecation. We illustrate the potential routes of transmission of COVID-19 and other fecal pathogens via human feces in communities practicing open defecation. Here, poor hand hygiene, contaminated shoes and objects, mechanical vectors, and outdoor human activities can all contribute to fecal transmission. Other risk factors include squat pans with lidless designs and open flushing mechanisms, in-cubicle open waste bins, and the lack of water-sealing U-traps in squat toilets.

Solar heating to inactivate thermal-sensitive pathogenic microorganisms in vehicles: application to COVID-19.

Disinfection is a common practice to inhibit pathogens, yet success is limited by microbial adaptation and our poor knowledge of viral transmission, notably in the current COVID-19 pandemic. There is a need for alternative disinfection strategies and techniques that are adapted to the actual behavior of humans living in densely populated mega-cities. Here, high public circulation in shared passenger vehicles such as taxis, buses and personal cars represents a major risk of viral transmission due to confined space and commonly touched surfaces. Actual regulatory guidelines are not fully successful because they rely both on passengers' willingness to wear face masks and on drivers' willingness to disinfect cars after each shift or each ride with symptomatic individuals. Here we propose that passive solar heating, a sustainable technique that has been used in agronomy to kill weeds and soil pathogens, could inactivate the virus in vehicles during warm-to-hot weather within few minutes to half an hour at 50-60 °C. We measured temperatures in a white compact-size sedan left in a parking lot under direct sunlight. Air temperatures increased from 30 to 42-49 °C after 30 min and then reached a plateau at 52-57 °C after 90 min. Temperatures were about 3 °C higher in front versus back of the car and about 5 °C higher at face height compared to knee height. Since COVID-19 is inactivated in 30 min at 56 °C, our findings confirm that hot air generated passively by solar heating in enclosed spaces is a promising strategy of disinfection with benefits of no added costs, chemicals or worktime. Though this technique appears limited to hot climate, possible heating systems that work during parking time might be developed by vehicle makers to extend the technique to cold climates.

Unflushable or missing toilet paper, the dilemma for developing communities during the COVID-19 episode.

Unlike in developed countries, most public toilets in China do not provide toilet paper onsite and users must bring their toilet paper. Moreover, an open waste bin is placed in each user's cubicle to collect used toilet paper and tissues. Such practices, which are common in East Asia and central America, have induced a dilemma of toilet paper disposal because some municipalities have removed waste bins from public toilets to prevent virus transmission by fecal matter. As a consequence, users were forced to flush down their used toilet paper and tissues. Yet, it is unknown whether standard toilet paper can be flushed easily without causing issues in sewer operations. Here, we surveyed the conditions of toilets in university campus and other public facilities in different regions across China. We also evaluated the disintegration characteristics of toilet paper products both by conducting online surveys and by physical disintegration experiments. We found that only 15% of toilets provided toilet paper, while open waste bins occurred at nearly all sites. Further, our survey indicated that 82% of toilet paper products sold in China did not give any indication on their flushability, whereas 77% of US products did. Disintegration results showed that none of the five popular, best-selling toilet paper products passed the flushability standard. We propose strategies to solve the current toilet paper dilemma in developing communities.

Salvia miltiorrhiza Bge. (Danshen) for Inflammatory Bowel Disease: Clinical Evidence and Network Pharmacology-Based Strategy for Developing Supplementary Medical Application.

Inflammatory bowel disease (IBD) is a non-specific colorectal disease caused by multifaceted triggers. Although conventional treatments are effective in the management of IBD, high cost and frequent side effects limit their applications and have turned sufferers toward alternative and complementary approaches. Salvia miltiorrhiza Bge (Danshen) is an herbal medicine that reportedly alleviates the symptoms of IBD. A large body of research, including clinical trials in which Danshen-based products or botanical compounds were used, has unmasked its multiple mechanisms of action, but no review has focused on its efficacy as a treatment for IBD. Here, we discussed triggers of IBD, collected relevant clinical trials and analyzed experimental reports, in which bioactive compounds of Danshen attenuated rodent colitis in the management of intestinal integrity, gut microflora, cell death, immune conditions, cytokines, and free radicals. A network pharmacology approach was applied to describe sophisticated mechanisms in a holistic view. The safety of Danshen was also discussed. This review of evidence will help to better understand the potential benefits of Danshen for IBD treatment and provide insights for the development of innovative applications of Danshen.

Integrating Network Analysis and Metabolomics to Reveal Mechanism of Huaganjian Decoction in Treatment of Cholestatic Hepatic Injury.

Huaganjian decoction (HGJD) was first recorded in the classic "Jing Yue Quan Shu" during the Ming dynasty, and it has been extensively applied in clinical practice to treat liver diseases for over 300 years in China. However, its bioactive constituents and relevant pharmacological mechanism are still unclear. In this study, a strategy integrating network analysis and metabolomics was applied to reveal mechanism of HGJD in treating cholestatic hepatic injury (CHI). Firstly, we observed the therapeutic effect of HGJD against CHI with an alpha-naphthylisothiocyanate (ANIT) induced CHI rat model. Then, we utilized UPLC-Q-Exactive MS/MS method to analyze the serum migrant compounds of HGJD in CHI rats. Based on these compounds, network analysis was conducted to screen for potential active components, and key signaling pathways interrelated to therapeutic effect of HGJD. Meanwhile, serum metabolomics was utilized to investigate the underlying metabolic mechanism of HGJD against CHI. Finally, the predicted key pathway was verified by western blot and biochemical analysis using rat liver tissue from in vivo efficacy experiment. Our results showed that HGJD significantly alleviated ANIT induced CHI. Totally, 31 compounds originated from HGJD have been identified in the serum sample. PI3K/Akt/Nrf2 signaling pathway related to GSH synthesis was demonstrated as one of the major pathways interrelated to therapeutic effect of HGJD against CHI. This research supplied a helpful strategy to determine the potential bioactive compounds and mechanism of traditional Chinese medicine.