Diastereoselective Three-Component 1,3-Dipolar Cycloaddition to Access Functionalized ß-Tetrahydrocarboline- and Tetrahydroisoquinoline-Fused Spirooxindoles.

A chemselective catalyst-free three-component 1,3-dipolar cycloaddition has been described. The unique polycyclic THPI and THIQs were creatively employed as dipolarophiles, which led to the formation of functionalized ß-tetrahydrocarboline- and tetrahydroisoquinoline-fused spirooxindoles in 60-94% of yields with excellent diastereoselectivities (10: 1->99: 1 dr). This reaction not only realizes a concise THPI- or THIQs-based 1,3-dipolar cycloaddition, but also provides a practical strategy for the construction of two distinctive spirooxindole skeletons.

Size-resolved counting of circulating tumor cells on pinched flow-based microfluidic cytometry.

Precise cell detecting and counting is meaningful in circulating tumor cells (CTCs) analysis. In this work, a simple cyclic olefin copolymer (COC) microflow cytometer device was developed for size-resolved CTCs counting. The proposed device is constructed by a counting channel and a pinched injection unit having three channels. Through injection flow rate control, microspheres/cells can be focused into the centerline of the counting channel. Polystyrene microspheres of 3, 9, 15, and 20 µm were used for the microspheres focusing characterization. After coupling to laser-induced fluorescence detection technique, the proposed device was used for polystyrene microspheres counting and sizing. A count accuracy up to 97.6% was obtained for microspheres. Moreover, the proposed microflow cytometer was applied to CTCs detecting and counting. To mimic blood sample containing CTCs and CTCs mixture with different subtypes, an MDA-MB-231 (human breast cell line) spiked red blood cells sample and a mixture of MDA-MB-231 and MCF-7 (human breast cell line) sample were prepared, respectively, and then analyzed by the developed pinched flow-based microfluidic cytometry. The simple fabricated and easy operating COC microflow cytometer exhibits the potential in the point-of-care clinical application.

Spatiotemporal response of water quality in fragmented mangroves to anthropogenic activities and recommendations for restoration.

Mangroves have received substantial attention for their pivotal role as ecological barriers between land and sea, owing to their capacity to effectively capture considerable quantities of terrestrial pollutants. Mangrove fragmentation has been a widespread global trend. There is limited information on the water quality status of these small scattered mangrove patches in coastal sub-developed areas, coupled with a paucity of efficient and intuitive assessment methodologies. To address this gap, the Water Quality Index (WQI) was introduced to evaluate the spatiotemporal characteristics of mangrove water quality. The major sources of pollution and anthropogenic activities that affect mangrove water quality were identified. The results revealed an average WQI value of 44.1 ± 13.3 for mangrove patches, consistently indicating a "low" water quality classification throughout all seasons. Both the size and natural conditions impact the water quality of mangroves. The large artificial patch (WQI: 56.4 ± 7.61) and the natural patch (WQI: 46.6 ± 13.6) exhibited relatively superior water quality, while the WQI value of a size-equivalent artificial patch compared with the natural patch is 38.6 ± 11.8. Aquaculture was the primary human activity that adversely affected the water quality of mangroves, and the potential sources of pollution were rainfall runoff and river discharge. These findings elucidate the unfavorable water quality characteristics and dominant pollution of fragmented mangroves, and validate the applicability of the WQI method for long-term evaluation of the water quality in mangrove patches. This study provides a basis for decision-making in water quality assessment and management of coastal wetlands and marine ecosystems. Scientific guidance to the management for mangrove protection and restoration was offered, such as regulating aquaculture activities, controlling non-point source pollution, implementing mangrove reforestation by using native species in historical mangrove sites.

Clinical characteristics and prognosis of patients with idiopathic membranous nephropathy with kidney tubulointerstitial damage.

BACKGROUND: To investigate the clinical and kidney pathological features and prognosis of idiopathic membranous nephropathy (IMN) with kidney tubulointerstitial damage (TID). METHODS: Based on the presence or absence of kidney TID by kidney biopsy, 300 patients diagnosed with IMN were categorized into non-TID (TID-) and tubulointerstitial injury (TID+) groups. The clinical and pathological data were analyzed retrospectively. All patients were followed up for 6-24 months after treatment with glucocorticoids (GCs) combined with cyclophosphamide or GCs combined with calcineurin inhibitors (CNIs) to observe treatment effects on patient prognosis. RESULTS: The patients in the TID + group were older and more likely to be male. The 24-h urine protein, blood urea nitrogen, serum creatinine, cystatin C, ß2-microglobulin, and antiphospholipase A2 receptor antibody levels were higher than those in the TID - group and the pathological manifestations were more severe. After 1 year of follow-up, the overall response rate (complete response + partial response) in the TID + group was lower (66.67% vs. 80.89%, p = .022) than in the other. After combined GC and CNI therapy, the complete remission rate in the TID + group was significantly lower than that in the TID - group (13.79% vs. 35.46%, p = .022). The 24-h urine protein level was an independent risk factor for worsening kidney condition (p = .038). CONCLUSION: Patients with IMN with TID have more severe clinical manifestations and pathological damage and lower remission rates. IMN with TID is a risk factor for worsening kidney condition; however, it is not an independent risk factor.

Dipolarophile-Controlled Regioselective 1,3-Dipolar Cycloaddition: A Switchable Divergent Access to Functionalized N-Fused Pyrrolidinyl Spirooxindoles.

N-fused pyrrolidinyl spirooxindole belongs to a class of privileged heterocyclic scaffolds and is prevalent in natural alkaloids and synthetic pharmaceutical molecules. To realize the switchable synthesis of divergent N-fused pyrrolidinyl spirooxindoles for further biological activity evaluation via a substrate-controlled strategy, a chemically sustainable, catalysis-free, and dipolarophile-controlled three-component 1,3-dipolar cycloaddition of isatin-derived azomethine ylides with diverse dipolarophiles is described in this work. A total of 40 functionalized N-fused pyrrolidinyl spirooxindoles were synthesized in 76-95% yields with excellent diastereoselectivities (up to >99:1 dr). The scaffolds of these products can be well-controlled by employing different 1,4-enedione derivatives as dipolarophiles in EtOH at room temperature. This study provides an efficient strategy to afford a spectrum of natural-like and potentially bioactive N-fused pyrrolidinyl spirooxindoles.

Microfluidic Magnetic Spatial Confinement Strategy for the Enrichment and Ultrasensitive Detection of MCF-7 and Escherichia coli O157:H7.

A microfluidic magnetic spatial confinement strategy was developed and employed to realize an ultrasensitive cell immunoassay. The straight confined channels in poly(dimethylsiloxane)-glass hybrid microchips were used as the enrichment and detection chambers for the proposed microfluidic magnetic cell immunoassays (µMCI). To accomplish the µMCI, prepared magnetic cell immunocomplexes were introduced into microchannels and preconcentrated in the detection zone under a permanent magnet. The magnetic cell immunocomplexes were constructed from aptamer-/antibody-coated magnetic beads and antibody-linked horseradish peroxidase-labeled target cells to guarantee the specificity and enhance the detection signal generated from the enzyme reaction. The sensitivity enhancement of µMCI was confirmed in a one-dimensional space confined microchamber, especially in the analysis of cells having more enzyme conjugating sites on their surface. This spatial confinement strategy based µMCI was then applied for model cell detection in the microchannel, the limits of detection (LODs) were 2 cells/mL for MCF-7 and 34 colony-forming unit/mL for Escherichia coli O157:H7 (E. coli O157:H7), which corresponded to up to 1202-fold LOD sensitivity improvement compared to the results of the similar immunoassays in microwell plates. The satisfactory selectivity and reproducibility of the strategy were also obtained. Moreover, it enabled rare MCF-7 detection in whole blood and E. coli O157:H7 detection in milk after time-shortened incubation. Constructing an appropriate confined space, this strategy can be extended to detect various cells with higher sensitivity, which provides a valuable approach for rare cell detection in practical applications.

Enantioselective Total Synthesis of Spirotryprostatin A.

In this paper, we disclosed a novel enantioselective total synthesis of spirotryprostatin A (1) in 15 steps with a 7.4% total yield from commercially available 2-iodo-5-methoxyaniline and γ-butyrolactone. The key step features of this synthesis include the copper-catalyzed cascade reaction of o-iodoaniline derivatives with alkynone to introduce the quaternary carbon stereocenter and an aza-Michael tandem reaction to construct the spiro[pyrrolidine-3,3'-oxindole] moiety.

Synthesis and antitumor activity of novel hybrid compounds between 1,4-benzodioxane and imidazolium salts.

A series of novel hybrid compounds between 1,4-benzodioxane and imidazolium salts was designed and prepared. The compounds were evaluated in vitro against a panel of human tumor cell lines (K562, SMMC-7721, and A-549). The structure-activity relationship results demonstrated that the 2-methyl-benzimidazole or 5,6-dimethyl-benzimidazole ring and substitution of the imidazolyl-3-position with a 4-phenylphenacyl substituent were critical for promoting cytotoxic activity. Particularly, compound 25 was found to be the most potent compound with IC50 values of 1.06-8.31 µM against the three human tumor cell lines and exhibited higher selectivity to K562 and SMMC-7721 cells with IC50 values 4.5- and 4.7-fold lower than cisplatin. Moreover, compound 25 inhibited cell proliferation by inducing the G0/G1 cell cycle arrest and apoptosis in SMMC-7721 cells.

Controls for multi-temporal patterns of riverine nitrogen and phosphorus export to lake: Implications for catchment management by high-frequency observations.

Intensifying human activity coupled with climate change increase the transport of excess riverine nitrogen (N) and phosphorus (P) loading from catchment to lake, leading to eutrophication and harmful algal blooms worldwide. To improve understanding of multi-temporal patterns of riverine N and P export and their hydro-biogeochemical controls over both episodic events and long-term trend, we analyzed and interpreted high-frequency data of total nitrogen (TN), ammonia-nitrogen (NH4-N), and total phosphorus (TP) provided by an automatic water quality monitoring station in a typical agricultural catchment draining to Lake Chaohu, China. Mann-Kendall test revealed a significant decreasing trend of riverine N and P concentration most of the time during 2018-2020. At the sub-daily scale, intraday TN concentrations varied by more than 1 mg/L in 31.8% of the period. Monthly TN and TP concentrations were particularly high in December 2019, indicating combined effect of hydrologic (long dry antecedent period and subsequent intensive rainfall events) and anthropogenic controls (fertilization and agricultural drainage). Significantly higher TN concentrations in winter and TP concentrations in summer reflected coupled dominances of precipitation and temperature on hydrologic and biogeochemical processes. Rainfall events with very heavy intensity drove disproportionate N and P loads (more than 20% of the total export) in only 3.2% of the period. Moderate and very heavy events registered the highest TN and TP concentrations, respectively. Our results highlighted the importance of automatic water quality monitoring station to reveal dynamics of riverine N and P export, which may imply future nutrient loading abatement plans for lake-connected catchment.

Antibiotics along an alpine river and in the receiving lake with a catchment dominated by grazing husbandry.

The livestock breeding industries face overuse of antibiotics, which has been intensively studied in recent years. However, the occurrence and fate of antibiotics as well as their potential threats to the aquatic environments in alpine and arid regions remain unclear. This study investigated the relationship of the occurrence and concentrations of antibiotics between the Kaidu River and Bosten Lake in a typical alpine basin in China. Hot spots with antibiotic pollution source were explored. The antibiotic concentrations in river water and suspended sediment (SPS) were 2.20-99.4 ng/L and 1.03-176 ng/g. The dominant antibiotics were tetracyclines, sulphacetamide, and ofloxacin in river water and sulfonamides, clarithromycin, roxithromycin, and ofloxacin in SPS. The apparent differences in pollution sources and landscapes in different reaches led to the obvious spatial patterns of antibiotics in the Kaidu River. Higher partition coefficient of antibiotic between SPS and water phases for sulfonamides than tetracyclines was because that tetracyclines strongly responded to clay contents while sulfonamides significantly responded to organic carbon contents in SPS. There were significant differences in detected antibiotic categories between the river and the lake. Fluoroquinolones (especially ciprofloxacin and enrofloxacin) were detected in the lake while sulphacetamide was only detected in the river. Therefore, the surrounding husbandry and aquaculture around the Bosten Lake was an important antibiotic pollution source in addition to inputs from the Kaidu River. This research suggested that alpine lakes could be an important sink of antibiotics in alpine dry regions, and thus impose greater threats to the aquatic ecosystem.

Impact on social capital and learning engagement due to social media usage among the international students in the U.S.

International students who pursue their academic goals in United States are prone to difficulties when attempting to build social resources and adjust to the new culture. Social media is a practical means of connection due to its ease of use and accessibility. Previous research has indicated contradictory effects of social media use on academic engagement. In addition to the direct effect, this research examined social media use influences on international students' learning engagement by mediating social capital and cultural adjustment. A total of 209 international students completed a web-based survey distributed via e-mail and social media between November 2021 and May 2022. Data were analyzed using Structural Equation Model. Results showed that only purposely using social media to collaborate with learning counterparts or materials directly improves international students' learning engagement. Other uses of social media (e.g., expanding new resources, solidifying close relationships) have no significant direct effects. Nonetheless, they are essential to improving levels of learning engagement via the mediation of bridging capital (social resources attributed to expanding relationships) and students' cultural adjustment in the U.S. International students' bonding capital (social resources available through trustworthy relationships) and home cultural retention showed little direct or indirect effects on learning engagement. This study recognizes the importance of social resources and cultural adjustment for international students. Also, this study provides valuable information to educators and administrators, as there is a need to identify the underlying mechanisms to contribute feasible learning intervention approaches and alleviate negative effects for international students.

Transport and fate of antibiotics in a typical aqua-agricultural catchment explained by rainfall events: Implications for catchment management.

Antibiotics receive many concerns since their negative environmental impacts are being revealed, especially in aqua-agricultural areas. Rainfall events are responsible for transferring excess contaminants to receiving waters. However, the understanding of antibiotics transport and fate responding to rainfall events was constrained by limited event-based data and lacking integrated consideration of dissolved and particulate forms. We developed an intensive monitoring strategy to capture responses of fourteen antibiotics to different types of rainfall events and inter-event low flow periods. Pollutant-rich suspended particles, as high as 1471 ng/g, were found in low flow periods while the very heavy rainfall events and consecutive rainfall events stimulated the release of antibiotics from eroded soil particles to river water. Therefore, these rainfall events drove radical increase of dissolved antibiotic concentration up to 592 ng/L and total flux up to 25.0 g/d. Sulfonamides were particularly sensitive to rainfall events because of their residues in manure-applied agricultural lands. Transport dynamics of most antibiotics were accretion whereas only clarithromycin exhibited a dilution pattern by concentration-discharge relationships. Aquaculture ponds were inferred to significantly contribute tetracycline, oxytetracycline, and clarithromycin. Conventional contaminants were compared to discriminate potential sources of antibiotics and imply effective catchment management. The results provided novel insights into event-based drivers and dynamics of antibiotics and could lead to appropriate management strategy.

Restless abdomen: a spectrum or a phenotype variant of restless legs syndrome?

BACKGROUND: With the growing awareness of restless legs syndrome (RLS), sensory disorders similar to RLS but initially confined to the arms, abdomen, and perineum have been reported. One of them is restless abdomen, which refers to a restless sensation in abdomen. Our study is designed to evaluate the clinical phenotype of restless abdomen and investigate its relationship with RLS. METHODS: We enrolled 10 patients with restless abdomen according to RLS diagnostic criteria, excluding the requiring of leg involvement. Laboratory examinations were performed to exclude mimics and notable comorbidities. RESULTS: All 10 patients had RLS like symptoms in the abdomen and otherwise satisfied all other RLS diagnostic criteria, and responded to dopaminergic therapy. CONCLUSIONS: Neurologists and gastroenterologists should be aware that RLS-related restlessness can occur in extra-leg anatomy in the absence of episodes of worsening or augmentation of restlessness.

Improving the antioxidant and anti-tyrosinase activities of Stemonae Radix by solid-state fermentation with Mucor circinelloides T2-12.

Stemonae Radix, a medicinal and edible herb, has been reported to possess various pharmacological effects. In the present study, Stemonae Radix was fermented by fungi to improve the antioxidant and anti-tyrosinase activities. The results showed that Stemonae Radix fermented by Mucor circinelloides T2-12 exhibited two-folds more antioxidant and anti-tyrosinase activities than non-fermented material. The increased activity might be ascribed to the improvement of total phenolic content, hydrolyzation of glucosides and esters of phenolics and metabolism of saccharides according to ultraviolet and nuclear paramagnetic resonance spectroscopy. This paper suggested that fermenting Stemonae Radix with M. circinelloides T2-12 is effective to increase antioxidant and anti-tyrosinase effects and Stemonae Radix fermented by M. circinelloides T2-12 might be newly alternative of natural antioxidant and tyrosinase inhibitor. The present study is the first to report that pure strain fermentation processing is effective in improving the antioxidant and anti-tyrosinase activities of Stemonae Radix.

Magnetic Multiarm Scaffold for the One-Step Purification of Epitope-Specific Neutralizing Antibodies.

Epitope-specific neutralizing antibodies (EsAbs) are of prime importance in the diagnosis and treatment of various serious diseases. However, obtaining EsAbs by the monoclonal antibody technique involves time-consuming and sophisticated multistep procedures, and the epitopes of the resulting antibodies are often not explicit. It is also very challenging to isolate EsAbs from numerous kinds of total immunoglobulins because of nonspecific adsorption and low separation efficiency. Herein, a magnetic core@multiarm shell-epitope (M@A-E) bioconjugate was fabricated to enrich and isolate EsAbs from immune serums. This robust multiarm scaffold exhibits outstanding binding capacity and good resistance to nontarget adsorption and serves as a reservoir for the release and reloading of EsAbs for repeatable applications. The EsAbs yield per milligram of the M@A-E was about 30 µg, which was approximately twice that of commercially available beads (16 µg). After 10 cycles of loading and release in glycine buffer (0.1 M, pH 2.5), the M@A-E bioconjugates still showed relatively high specificity and capture capacity (20 µg) superior to the same amount of new, unused conventional ones. This strategy provides a promising platform for enriching and isolating substantial quantities of EsAbs, which have great potential for applications in the detection and treatment of critical illness.

A new menthane-type monoterpenoid from fermented Illigera aromatica with Clonostachys rogersoniana 828H2.

A new menthane-type monoterpenoid, illigerate E (1), as well as two known ones, (1R*,3R*,4S*,6R*)-6,8-dihydroxymenthol (2) and cis-4-hydroxy-5-(1-hydroxy-1-methylethyl)-2-methyl-2-cyclohexene-1-one (3), were isolated from fermented Illigera aromatica with Clonostachys rogersoniana 828H2. Their structures were identified by HRESIMS and 1D/2D NMR spectra. Their inhibitory effects of NO production in RAW 264.7 macrophages were estimated.

Characterization and source identification of tetracycline antibiotics in the drinking water sources of the lower Yangtze River.

The occurrence and spatio-temporal patterns of five tetracyclines (TCs) and six of their degradation products were investigated in twenty-eight drinking water sources along the lower Yangtze River (LYR) over dry, normal and flood seasons. Tetracycline (TC), oxytetracycline (OTC) and doxytetracycline (DXC) were the dominant antibiotics detected with the highest occurrence. The maximum concentrations of TC, OTC and DXC were found in dry season as 11.16, 18.98, and 56.09 ng/L, respectively, because of the low dilution, low degradation, and high consumption in this season. Cluster analysis indicated distinct variations in the TCs' compositional profiles in both space and time. OTC and its metabolites contributed 18.5-59.6% of the TC load in dry season, possibly due to the seasonally increased release of pharmaceutical OTCs from sewage effluents, but they were seldom detected in other seasons. Pollution load index analysis showed that tributaries carrying large amounts of veterinary TCs derived from breeding wastewater and untreated rural sewage contributed larger proportions of the TC load for most drinking water sources than sewage outlets. The contribution ratio of the TC load from tributaries (74.5%) was approximately three times higher than that from sewage discharges (25.5%). The study demonstrated that the control of load from tributaries is the key to mitigating TC pollution of the drinking water sources in the LYR. An effective source tracking method for evaluating the contribution of antibiotic load from multiple diffuse pollution origins and identifying the high-risk contamination sources was established for antibiotic management and control.

Variations in concentrations and bioavailability of heavy metals in rivers caused by water conservancy projects: Insights from water regulation of the Xiaolangdi Reservoir in the Yellow River.

Water regulation of the Xiaolangdi Reservoir of the Yellow River was chosen as a case to investigate variations in concentrations and bioavailability of heavy metals caused by water conservancy projects in rivers. Water and suspended sediment (SPS) samples were collected at downstream sampling sites along the river during this period. Concentrations and speciation of Zn, Cr, Cu, Ni, and Pb in water and SPS samples were analyzed, and their bioaccumulation was studied with Daphnia magna. This study indicated that the exchangeable and carbonate-bound fractions of heavy metals in SPS decreased along the studied stretch, and the dissolved heavy metal concentrations increased along the river with 1.6-15 folds. This is because sediment resuspension increased along the river during water regulation, giving rise to the increase of heavy metal release from SPS. The dissolved Zn, Cu, Ni, and Pb concentrations were significantly positively correlated with SPS concentrations, and their increase along the river was greater than Cr. The body burdens of heavy metals in D. magna exposed into samples collected from the reservoir outlet were 1.3-3.0 times lower than those from downstream stations, suggesting that the heavy metal bioavailability increased during water regulation. This should be considered in the reservoir operation.

PTENp1, a natural sponge of miR-21, mediates PTEN expression to inhibit the proliferation of oral squamous cell carcinoma.

PTENp1, non-coding RNA (ncRNA) pseudogene, is involved in oral squamous cell carcinoma (OSCC). The precise effects mediated by PTENp1 transcripts within intricate regulatory networks involving molecular interactions with ancestral gene PTEN and tumorigenicity in OSCC remain unclear. Here, we found that PTENp1 was aberrantly expressed in OSCC. There was a positive correlation between the expression levels of PTENp1 and PTEN. Further, we showed that PTENp1 acted as a competing endogenous RNA that protects PTEN transcripts from being inhibited by miR-21, and consequently inhibited proliferation and colony formation and triggered S-G2/M cell cycle arrest through the AKT pathway. Also, the homogeneous relationship between expression of PTENp1 and PTEN was confirmed in OSCC tumor xenografts. Finally, low expression of PTENp1 and PTEN was negatively associated with histological differentiation and OSCC prognosis. The present work provided the first evidence for the extraordinary crosstalk among PTENp1, PTEN, and miR-21, and rendered a new light on the treatment of OSCC. © 2016 Wiley Periodicals, Inc.

A comparison of surgical outcomes and complications between hemostatic devices for thyroid surgery: a network meta-analysis.

This meta-analysis compared harmonic scalpel and LigaSure® systems with the conventional clamp-and-tie technique in thyroidectomy. Medline, Cochrane, EMBASE, and Google Scholar databases were searched until December 30, 2015. Randomized controlled studies (RCTs) or two-arm prospective studies were included. The primary outcome was operation time. The data were evaluated both by pair-wise meta-analyses and network meta-analysis within a Bayesian framework using Markov chain Monte Carlo methods. Compared with the conventional hemostasis, there was a significant reduction in operation time with harmonic scalpel (HS) and LigaSure (LS) (difference in means = -24.27 min, 95 % CI -28.11 to -20.44 min, P < 0.001; and difference in means = -13.08 min, 95 % CI -16.88 to -9.27 min, P < 0.001, respectively). For total thyroidectomy and hemi-thyroidectomy, subgroup pair-wise meta-analyses found a reduction of 26.31 and 21.90 min in operation time for harmonic scalpel, and a reduction of 12.77 and 17.48 min for LigaSure, respectively. Among studies with mixed total and hemi-thyroidectomy, no significant difference in operation time was seen between harmonic scalpel and the conventional hemostasis (P = 0.313). Network meta-analysis also found harmonic scalpel and LigaSure to have less operation time than the conventional hemostasis, and that harmonic scalpel was associated with a significant 9.78 min reduction in operation time than LigaSure which was not seen in pair-wise comparison. Harmonic scalpel had significantly less risk of definitive recurrent laryngeal nerve palsy, intra-operation blood loss, and post-operation bleeding than the conventional hemostasis. LigaSure was associated with significantly less intra-operative blood loss than the conventional hemostasis (P = 0.023). There was no significant difference among three different procedures in rates of transient recurrent laryngeal nerve palsy. This study found that harmonic scalpel and LigaSure decreased operation time compared with the conventional hemostasis and that harmonic scalpels was associated with the lowest operation time.