Maternal and Fetal Outcomes in Pulmonary Hypertension During Pregnancy: A Contemporary Nationwide Analysis.

BACKGROUND: Pulmonary hypertension (PH) disproportionately affects women, presenting challenges during pregnancy. Historically, patients with PH are advised to avoid pregnancy; however, recent reports have indicated that the incidence of adverse events in pregnant females with PH may be lower than previously reported. METHODS: We conducted a retrospective cohort study in pregnant patients with PH using the National Readmission Database from January 1, 2016, to December 31, 2020. PH was categorized according to the World Health Organization (WHO) classification. Primary endpoints include maternal mortality and 30-day non-elective readmission rate. Other adverse short term maternal (cardiovascular and obstetric) and fetal outcomes were also analyzed. RESULTS: Among 9,922,142 pregnant women, 3,532 (0.04%) had pulmonary hypertension (PH), with Group 1 PH noted in 1,833 (51.9%), Group 2 PH in 676 (19.1%), Group 3 PH in 604 (17.1%), Group 4 PH in 23 (0.7%), Group 5 PH in 98 (2.8%), and multifactorial PH in 298 (8.4%). PH patients exhibited higher rates of adverse cardiovascular events (15.7% vs. 0.3% without PH, p < 0.001) and mortality (0.9% vs. 0.01% without PH, p < 0.001). Mixed PH and Group 2 PH had the highest prevalence of adverse cardiovascular events among WHO PH groups. Patients with PH had a significantly higher non-elective 30-day readmission rate (10.4% vs. 2.3%) and maternal adverse obstetric events (24.2% vs. 9.1%) compared to those without PH (p < 0.001) (Figure 1). CONCLUSION: Pregnant women with PH had significantly higher adverse event rates, including in-hospital maternal mortality (85-fold), compared to those without PH.

Prevalent arbuscular mycorrhizae in roots and highly variable mycobiome in leaves of epiphytic subtropical fern Ophioderma pendulum.

PREMISE: Endophytic and mycorrhizal fungi are crucial in facilitating plant nutrition acquisition and stress tolerance. In epiphytic habitats, plants face nutrition and water stress, but their roots are mostly nonmycorrhizal and especially lacking in arbuscular mycorrhizal associations. Ophioderma pendulum is an epiphytic fern with a partially mycoheterotrophic lifestyle, likely heavily reliant on symbiotic fungi. To characterize fungal associations in the sporophyte of O. pendulum, we focused on leaves and roots of O. pendulum, seeking to reveal the fungal communities in these organs. METHODS: Roots and leaves from O. pendulum in a subtropical forest were examined microscopically to observe the morphology of fungal structures and determine the percentage of various fungal structures in host tissues. Fungal composition was profiled using metabarcoding techniques that targeted ITS2 of the nuclear ribosomal DNA. RESULTS: Roots were consistently colonized by arbuscular mycorrhizal fungi (Glomeromycota), especially Acaulospora. Unlike previous findings on epiphytic ferns, dark septate endophytes were rare in O. pendulum roots. Leaves were predominantly colonized by Ascomycota fungi, specifically the classes Dothideomycetes (46.88%), Eurotiomycetes (11.51%), Sordariomycetes (6.23%), and Leotiomycetes (6.14%). Across sampling sites, fungal community compositions were similar in the roots but differed significantly in the leaves. CONCLUSIONS: Ophioderma pendulum maintains stable, single-taxon-dominant communities in the roots, primarily featuring arbuscular mycorrhizal fungi, whereas the leaves may harbor opportunistic fungal colonizers. Our study underlines the significance of mycorrhizal fungi in the adaptation of epiphytic ferns.

Effects of combined traditional Chinese medicine therapy in patients of lower limbs injuries with osteoporosis: A retrospective paired cohort study.

Studies have confirmed that the health hazards of patients with lower limb injuries combined with osteoporosis are more obvious. This study is mainly based on the Taiwan National Health Insurance Database, and through big data analysis, it shows that the combined treatment of traditional Chinese medicine (TCM) is helpful to the health of patients with lower limb injuries combined with osteoporosis. A total of 9989 combined TCM-treated patients and 19,978 2:1 sex-, age-, and index-year-matched controls who did not receive TCM treatment were selected from the Taiwan National Health Insurance Database. Cox proportional hazards analyzes were performed to compare fracture surgery, inpatient, and all-cause mortality during a mean follow-up period of 17 years. A total of 5406/8601/2564 enrolled-subjects (14.11%/25.46%/5.53%) had fracture surgery/inpatient/all-cause mortality, including 1409/2543/552 in the combined TCM group (14.11%/25.46%/5.53%) and 3997/6058/2012 in the control group (20.01%/30.32%/10.07%). Cox proportional hazard regression analysis showed a lower rate of fracture surgery, inpatient and all-cause mortality for subjects in the combined TCM group (adjusted hazard ratios [HR] = 0.723; 95% confidence intervals [CI] = 0.604-0.810, P < .001; adjusted hazard ratios [HR] = 0.803; 95% CI = 0.712-0.950, P = .001; adjusted HR = 0.842; 95% CI = 0.731-0.953, P = .007, respectively). After 10 years of follow-up, the cumulative incidence of fracture surgery in patients combining TCM treatment seems to be half of that without combining TCM treatment those are shown in Kaplan-Meier analysis with statistically significant (log rank, P < .001, P < .001, and P = .010, respectively). This study hopes to provide clinicians with the option of combined TCM treatment for patients of lower limbs injuries combined with osteoporosis, so that such patients will be associate with a lower risk of fracture surgery, inpatient or all-cause mortality.

Gut Microbiota Modulation of Short Bowel Syndrome and the Gut-Brain Axis.

Short bowel syndrome (SBS) is a condition that results from a reduction in the length of the intestine or its functional capacity. SBS patients can have significant side effects and complications, the etiology of which remains ill-defined. Thus, facilitating intestinal adaptation in SBS remains a major research focus. Emerging data supports the role of the gut microbiome in modulating disease progression. There has been ongoing debate on defining a "healthy" gut microbiome, which has led to many studies analyzing the bacterial composition and shifts that occur in gastrointestinal disease states such as SBS and the resulting systemic effects. In SBS, it has also been found that microbial shifts are highly variable and dependent on many factors, including the anatomical location of bowel resection, length, and structure of the remnant bowel, as well as associated small intestinal bacterial overgrowth (SIBO). Recent data also notes a bidirectional communication that occurs between enteric and central nervous systems called the gut-brain axis (GBA), which is regulated by the gut microbes. Ultimately, the role of the microbiome in disease states such as SBS have many clinical implications and warrant further investigation. The focus of this review is to characterize the role of the gut microbiota in short bowel syndrome and its impact on the GBA, as well as the therapeutic potential of altering the microbiome.

Polarized localization of phosphatidylserine in the endothelium regulates Kir2.1.

Lipid regulation of ion channels is largely explored using in silico modeling with minimal experimentation in intact tissue; thus, the functional consequences of these predicted lipid-channel interactions within native cellular environments remain elusive. The goal of this study is to investigate how lipid regulation of endothelial Kir2.1 - an inwardly rectifying potassium channel that regulates membrane hyperpolarization - contributes to vasodilation in resistance arteries. First, we show that phosphatidylserine (PS) localizes to a specific subpopulation of myoendothelial junctions (MEJs), crucial signaling microdomains that regulate vasodilation in resistance arteries, and in silico data have implied that PS may compete with phosphatidylinositol 4,5-bisphosphate (PIP2) binding on Kir2.1. We found that Kir2.1-MEJs also contained PS, possibly indicating an interaction where PS regulates Kir2.1. Electrophysiology experiments on HEK cells demonstrate that PS blocks PIP2 activation of Kir2.1 and that addition of exogenous PS blocks PIP2-mediated Kir2.1 vasodilation in resistance arteries. Using a mouse model lacking canonical MEJs in resistance arteries (Elnfl/fl/Cdh5-Cre), PS localization in endothelium was disrupted and PIP2 activation of Kir2.1 was significantly increased. Taken together, our data suggest that PS enrichment to MEJs inhibits PIP2-mediated activation of Kir2.1 to tightly regulate changes in arterial diameter, and they demonstrate that the intracellular lipid localization within the endothelium is an important determinant of vascular function.

Progerin induces a phenotypic switch in vascular smooth muscle cells and triggers replication stress and an aging-associated secretory signature.

Hutchinson-Gilford progeria syndrome is a premature aging disease caused by LMNA gene mutation and the production of a truncated prelamin A protein "progerin" that elicits cellular and organismal toxicity. Progerin accumulates in the vasculature, being especially detrimental for vascular smooth muscle cells (VSMC). Vessel stiffening and aortic atherosclerosis in HGPS patients are accompanied by VSMC depletion in the medial layer, altered extracellular matrix (ECM), and thickening of the adventitial layer. Mechanisms whereby progerin causes massive VSMC loss and vessel alterations remain poorly understood. Mature VSMC retain phenotypic plasticity and can switch to a synthetic/proliferative phenotype. Here, we show that progerin expression in human and mouse VSMC causes a switch towards the synthetic phenotype. This switch elicits some level of replication stress in normal cells, which is exacerbated in the presence of progerin, leading to telomere fragility, genomic instability, and ultimately VSMC death. Calcitriol prevents replication stress, telomere fragility, and genomic instability, reducing VSMC death. In addition, RNA-seq analysis shows induction of a profibrotic and pro-inflammatory aging-associated secretory phenotype upon progerin expression in human primary VSMC. Our data suggest that phenotypic switch-induced replication stress might be an underlying cause of VSMC loss in progeria, which together with loss of contractile features and gain of profibrotic and pro-inflammatory signatures contribute to vascular stiffness in HGPS.

Novel Therapeutic Approaches for Mitigating Complications in Short Bowel Syndrome.

Short bowel syndrome (SBS) is a particularly serious condition in which the small intestine does not absorb sufficient nutrients for biological needs, resulting in severe illness and potentially death if not treated. Given the important role of the gut in many signaling cascades throughout the body, SBS results in disruption of many pathways and imbalances in various hormones. Due to the inability to meet sufficient nutritional needs, an intravenous form of nutrition, total parental nutrition (TPN), is administered. However, TPN presents difficulties such as severe liver injury and altered signaling secondary to the continued lack of luminal contents. This manuscript aims to summarize relevant studies into the systemic effects of TPN on systems such as the gut-brain, gut-lung, and gut-liver axis, as well as present novel therapeutics currently under use or investigation as mitigation strategies for TPN induced injury.

Characteristics of the Cytotoxicity of Taraxacum mongolicum and Taraxacum formosanum in Human Breast Cancer Cells.

Breast cancer is a highly heterogeneous disease that has been clinically divided into three main subtypes: estrogen receptor (ER)- and progesterone receptor (PR)-positive, human epidermal growth factor receptor 2 (HER 2)-positive, and triple-negative breast cancer (TNBC). With its high metastatic potential and resistance to endocrine therapy, HER 2-targeted therapy, and chemotherapy, TNBC represents an enormous clinical challenge. The genus Taraxacum is used to treat breast cancer in traditional medicine. Here, we applied aqueous extracts from two Taraxacum species, T. mongolicum and T. formosanum, to compare their potential antitumor effects against three human breast cancer cell lines: MDA-MB-231 (ER-, PR-, and HER2-), ZR-75-1 (ER+, PR+/-, and HER2-), and MCF-7 (ER+, PR+, and HER2-). Our results show that T. mongolicum exerted cytotoxic effects against MDA-MB-231 cells, including the induction of apoptosis, the reduction of cell proliferation, the disruption of the mitochondrial membrane potential, and/or the downregulation of the oxygen consumption rate. Both T. mongolicum and T. formosanum decreased cell migration and colony formation in the three cell-lines and exerted suppressive effects on MCF-7 cell proliferation based on metabolic activity and BrdU incorporation, but an enhanced proliferation of ZR-75-1 cells based on BrdU incorporation. T. formosanum induced ribotoxic stress in MDA-MB-231and ZR-75-1 cells; T. mongolicum did not. In summary, these findings suggest that T. mongolicum showed greater cytotoxicity against all three tested breast cancer cell lines, especially the TNBC MDA-MB-231 cell line.

Anti-inflammatory butanolides and lignanoids from the root of Machilus zuihoensis var. mushaensis.

From the anti-inflammatory screening of Formosan Lauraceous plants, the methanolic extract of the root of Machilus zuihoensis var. mushaensis stood out for its potent inhibitory activity toward superoxide anion and elastase release in human neutrophils. Bioassay-guided fractionation of the root of M. zuihoensis var. mushaensis led to eight new compounds, including two butanolides (1-2), five lignanoids (3-7), and one sesquiterpenoid (8), along with 50 known compounds (9-58). Structures of these compounds were elucidated by NMR, UV, IR, CD, and MS analyses. Thirty-two isolates were evaluated for their anti-inflammatory activity. Among them, 9, 20, 27, 28, 30, 31, 35, and 40 exhibited significant superoxide anion generation inhibition selectively (IC50 value < 7.4 µM), 15 and 19 showed selective inhibition toward elastase release (IC50 value < 8.0 µM). Moreover, 3, 16, 21, and 22 simultaneously displayed superoxide anion generation and elastase release inhibition. It is worth mentioning that 21 and 22 showed more potent inhibitory activities (IC50 < 1.0 µM) on superoxide anion than the positive control, LY294002. Further quantitative HPLC analysis indicated the content of 21 and 22 were 0.90 and 3.04 mg/g (w/w) in the ethyl-acetate layer of the root of M. zuihoensis var. mushaensis, respectively. Altogether, M. zuihoensis var. mushaensis revealed a potential for developing the botanical new drug against inflammation-related disease.

An innovative reuse of bottom ash from municipal solid waste incinerators as substrates of constructed wetlands.

The incineration of municipal solid waste has been important in waste management, but it raises another environmental issue concerning residue treatment. This study describes an innovative use of naturally aged incineration bottom ash (AIBA) as an alternative substrate for horizontal subsurface flow (HSSF) constructed wetlands (CW). Although experimental results from a period lasting for 396 days only revealed slightly higher removal ratios in HSSF with AIBA (HSSF-E) than in HSSF-traditional pebble beds (HSSF-C), increasing from 67% to 76% for BOD, 44%-51% for TKN, 47%-54% for NH3-N, and 44%-52% for TN. The data indicate that the use of AIBA in HSSF CW can achieves a certain removal efficiency of BOD and nitrogen species. Interestingly, the total phosphorus removal rates also increased significantly from 20% in HSSF-C to 36% in HSSF-E. These observations on the use of AIBA in HSSF CW confirmed that AIBA is a suitable alternative for use as a substrate for HSSF CWs and identified an additional way to reuse incineration bottom ash. Design criteria for a CW using AIBA as a partial substrate is proposed to improve the pollutant removal performance of HSSF CWs.

Curbing COVID-19 progression and mortality with traditional Chinese medicine among hospitalized patients with COVID-19: A propensity score-matched analysis.

BACKGROUND: Viral- and host-targeted traditional Chinese medicine (TCM) formulae NRICM101 and NRICM102 were administered to hospitalized patients with COVID-19 during the mid-2021 outbreak in Taiwan. We report the outcomes by measuring the risks of intubation or admission to intensive care unit (ICU) for patients requiring no oxygen support, and death for those requiring oxygen therapy. METHODS: This multicenter retrospective study retrieved data of 840 patients admitted to 9 hospitals between May 1 and July 26, 2021. After propensity score matching, 302 patients (151 received NRICM101 and 151 did not) and 246 patients (123 received NRICM102 and 123 did not) were included in the analysis to assess relative risks. RESULTS: During the 30-day observation period, no endpoint occurred in the patients receiving NRICM101 plus usual care while 14 (9.27%) in the group receiving only usual care were intubated or admitted to ICU. The numbers of deceased patients were 7 (5.69%) in the group receiving NRICM102 plus usual care and 27 (21.95%) in the usual care group. No patients receiving NRICM101 transitioned to a more severe status; NRICM102 users were 74.07% less likely to die than non-users (relative risk= 25.93%, 95% confidence interval 11.73%-57.29%). CONCLUSION: NRICM101 and NRICM102 were significantly associated with a lower risk of intubation/ICU admission or death among patients with mild-to-severe COVID-19. This study provides real-world evidence of adopting broad-spectrum oral therapeutics and shortening the gap between outbreak and effective response. It offers a new vision in our preparation for future pandemics.

Anticancer Effects of Taraxacum via Cell Cycle Arrest, Necrosis, Apoptosis, and Endoplasmic Reticulum Stress.

Dandelion (Taraxacum species) is a wild plant with over 2500 species. Flavonoids, phenolic compounds, saponins, sesquiterpenes, and sugars have been detected in the organs of Taraxacum, and for centuries it has been used in traditional medicine for the relief and treatment of various diseases. However, details of its working mechanism remain unclear. Bioactive compounds in herbal extracts generally have low yields, which makes their isolation and purification intensive in terms of time and cost. Here, to assess their versatility and safety, we applied aqueous extracts of two species of Taraxacum, T. mongolicum and T. formosanum, including extracts of both fresh and dried T. formosanum, to compare their potential antitumor effects on HeLa human cervical cancer cells, three liver cancer cell lines, and one normal liver cell line. After being treated with a lower dose of Taraxacum, the upregulation of subG1 and S populations, as well as increased levels of p-eIF2[Formula: see text]-to-eIF2[Formula: see text] ratio, were observed in HeLa cells, whereas the downregulation of S population and the absence of mRNA expressions were detected in HeLa cells when being treated with a higher dose of Taraxacum. These results indicated that Taraxacumcould induce apoptosis and endoplasmic reticulum stress while suppressing proliferation, transcription, colony formation, migration, and invasion. What's more, we also found that the effects of fresh T. formosanum were much stronger than that of T. mongolicumin HeLa cells. Based on these results, we suggest that T. formosanum may contain specific compound(s) that are potentially useful for cancer therapy. However, much work remains to identify these effective compounds for the future application of Taraxacumto cancer therapy.

Elastin, arterial mechanics, and stenosis.

Elastin is a long-lived extracellular matrix protein that is organized into elastic fibers that provide elasticity to the arterial wall, allowing stretch and recoil with each cardiac cycle. By forming lamellar units with smooth muscle cells, elastic fibers transduce tissue-level mechanics to cell-level changes through mechanobiological signaling. Altered amounts or assembly of elastic fibers leads to changes in arterial structure and mechanical behavior that compromise cardiovascular function. In particular, genetic mutations in the elastin gene (ELN) that reduce elastin protein levels are associated with focal arterial stenosis, or narrowing of the arterial lumen, such as that seen in supravalvular aortic stenosis and Williams-Beuren syndrome. Global reduction of Eln levels in mice allows investigation of the tissue- and cell-level arterial mechanical changes and associated alterations in smooth muscle cell phenotype that may contribute to stenosis formation. A loxP-floxed Eln allele in mice highlights cell type- and developmental origin-specific mechanobiological effects of reduced elastin amounts. Eln production is required in distinct cell types for elastic layer formation in different parts of the mouse vasculature. Eln deletion in smooth muscle cells from different developmental origins in the ascending aorta leads to characteristic patterns of vascular stenosis and neointima. Dissecting the mechanobiological signaling associated with local Eln depletion and subsequent smooth muscle cell response may help develop new therapeutic interventions for elastin-related diseases.

Traditional Chinese medicine attenuates hospitalization and mortality risks in diabetic patients with carcinoma in situ in Taiwan.

BACKGROUND: Diabetic patients are at high risk of developing cancer. Traditional Chinese medicine (TCM) has become increasingly popular as an adjuvant treatment for patients with chronic diseases, and some studies have identified its beneficial effect in diabetic patients with cancer. The purpoes of this study was to outline the potential of TCM to attenuate hospitalization and mortality rates in diabetic patients with carcinoma in situ (CIS). METHODS: A total of 6,987 diabetic subjects with CIS under TCM therapy were selected from the National Health Insurance Research Database of Taiwan, along with 38,800 of 1:1 sex-, age-, and index year-matched controls without TCM therapy. Cox proportional hazard analysis was conducted to compare hospitalization and mortality rates during an average of 15 years of follow-up. RESULTS: A total of 3,999/1,393 enrolled-subjects (28.62%/9.97%) had hospitalization/mortality, including 1,777/661 in the TCM group (25.43%/9.46%) and 2,222/732 in the control group (31.80%/10.48%). Cox proportional hazard regression analysis showed a lower rate of hospitalization and mortality for subjects in the TCM group (adjusted HR=0.536; 95% CI=0.367-0.780, P<0.001; adjusted HR=0.783; 95% CI=0.574-0.974, P = 0.022). Kaplan-Meier analysis showed that the cumulative risk of hospitalization and mortality in the case and control groups was significantly different (log rank, P<0.001 and P = 0.011, respectively). CONCLUSIONS: Diabetic patients with CIS under TCM therapy were associated with lower hospitalization and mortality rates compared to those without TCM therapy. Thus, TCM application may reduce the burden of national medical resources.

Vascular Smooth Muscle Cell Subpopulations and Neointimal Formation in Mouse Models of Elastin Insufficiency.

OBJECTIVE: Using a mouse model of Eln (elastin) insufficiency that spontaneously develops neointima in the ascending aorta, we sought to understand the origin and phenotypic heterogeneity of smooth muscle cells (SMCs) contributing to intimal hyperplasia. We were also interested in exploring how vascular cells adapt to the absence of Eln. Approach and Results: We used single-cell sequencing together with lineage-specific cell labeling to identify neointimal cell populations in a noninjury, genetic model of neointimal formation. Inactivating Eln production in vascular SMCs results in rapid intimal hyperplasia around breaks in the ascending aorta's internal elastic lamina. Using lineage-specific Cre drivers to both lineage mark and inactivate Eln expression in the secondary heart field and neural crest aortic SMCs, we found that cells with a secondary heart field lineage are significant contributors to neointima formation. We also identified a small population of secondary heart field-derived SMCs underneath and adjacent to the internal elastic lamina. Within the neointima of SMC-Eln knockout mice, 2 unique SMC populations were identified that are transcriptionally different from other SMCs. While these cells had a distinct gene signature, they expressed several genes identified in other studies of neointimal lesions, suggesting that some mechanisms underlying neointima formation in Eln insufficiency are shared with adult vessel injury models. CONCLUSIONS: These results highlight the unique developmental origin and transcriptional signature of cells contributing to neointima in the ascending aorta. Our findings also show that the absence of Eln, or changes in elastic fiber integrity, influences the SMC biological niche in ways that lead to altered cell phenotypes.

Tissue-specific smooth muscle cell subtypes identified by transcriptional profiling.

Smooth muscle cells (SMCs) are specialized cells present in many organs where they serve diverse tissue-specific functions. Using the Tabula Muris compendium of single-cell RNA sequencing data, we extracted individual SMC transcriptomes from eight mouse tissues to investigate the transcriptomic landscape of tissue-specific SMCs. We identified marker genes, signaling pathways, and biological processes enriched in tissue-specific SMCs, and inferred potential ligand-receptor interaction between SMC and other cell types. Our analysis also identified sex differences in SMC gene expression in different tissues. Lastly, we used unsupervised clustering to identify novel SMC subtypes based on their downstream targets of transcription factors. Our results highlight the variable SMC phenotypes and underscore this cell's remarkable adaptability to contribute to diverse tissue function.

Flower-visiting insects of genus Melastoma (Myrtales: Melastomataceae) at the Fushan Botanical Garden, Taiwan.

BACKGROUND: We investigated the diversity and behaviour of insects that visit flowers of four native Melastoma (Family Melastomataceae) species of Taiwan and a horticultural hybrid Melastoma species at the Fushan Botanical Garden, Taiwan biweekly from May to August 2020. Visits of flower-visiting insects were classified into seven behavioural categories, based on the insects' behaviour and positions on the flower. The data are further assigned into four insect-flower interactions, namely pollination, herbivory, commensalism and neutralism. Our goal is to provide baseline data of insect-plant interactions of Melastoma, which is a common, but understudied plant genus in the country. NEW INFORMATION: A total of 1,289 visits to flowers were recorded by at least 63 insect morphospecies belonging to seven orders. The number of insect species recorded per Melastoma species ranged from 9 to 39. Visiting, sonication and passing were the three most frequently recorded types of behaviour, collectively accounting for 90.2% (n = 1,240) of the total observations. Pollination was the most dominant insect-flower interaction, accounting for 70.2% of the total observations, followed by neutralism (20.0%), herbivory (6.3%) and commensalism (3.5%). Sweat bees of the genera Lasioglossum and Maculonomia (Hymenoptera: Halictidae) are considered key pollinators to Melastoma species in Fushan Botanical Garden, based on their high number of visits and sonication behaviour. Our study provides the first list of insects that visit the flowers of all Taiwan's known Melastoma species and description of their interactions with the plants.

A traditional Chinese medicine formula NRICM101 to target COVID-19 through multiple pathways: A bedside-to-bench study.

COVID-19 is a global pandemic, with over 50 million confirmed cases and 1.2 million deaths as of November 11, 2020. No therapies or vaccines so far are recommended to treat or prevent the new coronavirus. A novel traditional Chinese medicine formula, Taiwan Chingguan Yihau (NRICM101), has been administered to patients with COVID-19 in Taiwan since April 2020. Its clinical outcomes and pharmacology have been evaluated. Among 33 patients with confirmed COVID-19 admitted in two medical centers, those (n = 12) who were older, sicker, with more co-existing conditions and showing no improvement after 21 days of hospitalization were given NRICM101. They achieved 3 consecutive negative results within a median of 9 days and reported no adverse events. Pharmacological assays demonstrated the effects of the formula in inhibiting the spike protein/ACE2 interaction, 3CL protease activity, viral plaque formation, and production of cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α. This bedside-to-bench study suggests that NRICM101 may disrupt disease progression through its antiviral and anti-inflammatory properties, offering promise as a multi-target agent for the prevention and treatment of COVID-19.

Application of an innovative front aeration and internal recirculation strategy to improve the removal of pollutants in subsurface flow constructed wetlands.

The pollutant removal performance of traditional horizontal subsurface flow (HSSF) constructed wetlands (CWs) is limited because of the dissolved oxygen (DO) supply is insufficient. The aeration of HSSF CWs usually improves their pollutant removal performance, but a high DO induces the accumulation of nitrate-nitrogen (NO3--N) and suppresses the improvement of total nitrogen (TN) removal. In this study, an integrated solution that involved in-tank front aeration and internal recirculation (FAIR) was used to improve the pollutant removal performance of HSSF CWs. Based on the experimental results, the FAIR system significantly increased the removal efficiencies of biochemical oxygen demand (BOD) from 53.8-76.0% to 82.0-91.7% and reduced the BOD concentration in the effluent to below 10 mg L-1. The removal efficiency of ammonia-nitrogen (NH3-N) increased from 15.1-78.3% to 98.5-98.6% while the removal efficiencies of the total Kjeldahl nitrogen (TKN) of the control and FAIR HSSF CWs were 18.2-77.1% and 93.5-94.3%, respectively. HSSF CWs with FAIR outperformed aerated HSSF CWs in the removal of NH3-N and TKN. The effects of two recirculation flow ratios (Rr = recirculation flow rate/influent flow rate), 14.3 and 3.0, on the improvement of pollutant removal performance were investigated. The lower Rr did not significantly affect the improvement of BOD, NH3-N, and TKN, but a higher Rr resulted in more severe accumulation of NO3--N. The removal efficiency of TN in control HSSF CWs ranged from 20.4% to 75.5%, and in the FAIR HSSF CW was 71.6% for Rr = 14.3 and 81.3% for Rr = 3.0. However, the FAIR system did not enhance the removal performance of total phosphorus, suggesting that the DO level and internal recirculation were not dominant mechanisms for the removal of phosphorous. The easy maintenance of the FAIR system made it a superior modification for improving the pollutant removal performance of HSSF CWs.