Measurement of an Analyte Concentration in Test Solution by Using Helmholtz Resonator for Biosensor Applications.

In this paper, an indirect method of measuring an analyte concentration in a test solution using the resonant frequency change of a Helmholtz resonator is proposed, using a novel architecture of Helmholtz resonator filled with two kinds of fluids (fixed fluid and test solution). Since the analyte concentration yields changes of density and sound speed of the test solution, the resonant frequency of the proposed Helmholtz resonator is affected by the analyte concentration of the test solution. From this effect, the analyte concentration of the test solution can be measured by the spectrum of acoustic resonance of the Helmholtz resonator. The experiment was done using a 3D-printed Helmholtz resonator system with an acoustic power source and detectors, which is consistent with analytical results and showed that the analyte concentration can be measured with higher sensitivity compared to conventional cantilever-type sensors. As an example application, the possibility of measuring glucose concentration of human blood was demonstrated, showing higher sensitivity and relatively low frequency range compared to previous resonance based methods.

How to simulate future scenarios of urban stormwater management? A novel framework coupling climate change, urbanization, and green stormwater infrastructure development.

Climate change, urbanization, and green stormwater infrastructure (GSI) planning policies lead to uncertainties in future urban sustainability. Coupling multiple influencing factors such as climate change, urbanization, and GSI development, this study proposes a novel framework for simulating future scenarios of urban stormwater. Subsequently, the changes in annual surface runoff and runoff pollutants in Shanghai's new and old urban areas were compared and analyzed based on 35 typical future and seven baseline scenarios. The following results were obtained: 1) The runoff control rate of the new urban area was significantly higher than that of the old urban area before GSI construction. After GSI construction, both areas could control stormwater runoff and pollutants, while the decline in efficiency in GSI facilities enormously impacted the old area. 2) Surface runoff in the new urban area was mainly affected by urbanization, while climate change was a major factor in the old urban area; runoff pollutants in new and old urban areas were mainly affected by urbanization, and the change in pollutants in new areas was more pronounced. 3) GSI facilities were unlikely to guarantee the quantity and quality of water resources, especially in scenarios where the efficiency of GSI facilities decreases. In old urban areas, the more extreme climate change and urbanization were, the more significant the effect of improving stormwater management facilities. Our findings showed that future studies on stormwater management should specifically consider the different characteristics of new and old urban regions, pay attention to the maintenance and management of GSI facilities, and build adaptive strategies to cope with climate change, urbanization, and GSI facility destruction.

MRNA Profiling Involved in Triggering of STAT1 with Regulatory Involvement of IRF7, PTPRF, and miR-145p in Patients Suffering from Gall Bladder Carcinoma.

BACKGROUND: Gall Bladder Cancer (GBC) is a type of extremely malignant tumor, which has high incidences of mortality. There is rare information about its mechanisms of invasion and gene expression regulations. microRNA-155 (miR-155) has mostly been reported to be over expressed in cases of solid tumors and hematopoietic malignancies. In this study, we have investigated the role and clinical significance of miR-155 in a Chinese population suffering from GBC and compared the results with nonneoplastic inflammation. METHODS: Tissue specimens were collected on 50 patients of Gall Bladder Carcinoma and 10 patients suffering from nonneoplastic inflammation who have undergone surgeries at the Department of Pathology, Renji Hospital, Shanghai, from January 2019 to January 2020. We performed profiling of miR-155 expression in both nonneoplastic and gall bladder carcinoma tissues by QRT-PCR. RESULTS: Expression levels of miR-155 were found to be extremely high in GBC patients in comparison to the nonneoplastic tissues ( ∗ P < 0.05), as high miRNA is correlated with TNM stages. Further results noted were that miR-145-5p expressed genes mimic the gene expression of STAT1, a downregulation of IRF7 was noted in the GBC, and an activation of STAT1 was significantly noted in carcinoma cells of the gallbladder. Downregulation of PTPRF was also noted during the expression of miR-145. CONCLUSIONS: As downregulation of IRF7 is linked with low rates of survival, it was found that gall bladder carcinoma patients may face high mortality. The STAT-1 expression of unregulated in GBC patients was also noted.

Benzothiazines in organic synthesis. An approach to floresolide B.

The intramolecular conjugate addition of a sulfoximine carbanion to an α,ß-unsaturated ester results in the formation of a benzothiaine bearing a benzylic stereocenter with extremely high fidelity. We have used this methodology to complete a formal total synthesis of the antitumor agent (+)-floresolide B.

Oxidation of 4-methoxyanilines to 1,4-benzoquinones using ceric ammonium nitrate (CAN).

Treatment of substituted 4-methoxyanilines with ceric ammonium nitrate in a 1:1 mixture of water and acetonitrile resulted in formation of 1,4-benzoquinones in acceptable yields.

Study on the Mechanism of Capillary Leakage Caused by Hypoxia-Inducible Factor-1α through Inducing High Expression of Matrix Metalloproteinase-9.

PURPOSES: This study mainly explored the mechanism of capillary leakage caused by hypoxia-inducible factor-1α through inducing high expression of matrix metalloproteinase-9. Method. We established a monolayer endothelial cell model by culturing human umbilical vein endothelial cells (HUVEC) in vitro, used tumor necrosis factor (TNFα) and HIF-1α inhibitor 2-methoxyestradiol (2ME2) to act on HUVEC, and at the same time constructed siRNA-transfected HUVEC to interfere with the expression of HIF-1α. The permeability of monolayer endothelial cells was measured by transwell chamber method, the concentration of MMP-9 in the supernatant was measured by ELISA method, the expression of key molecules related to permeability (HIF- 1α, MMP-9, claudin-5, and ZO-1) was measured by RT-PCR and Western blot method, and the localization and expression of claudin-5 and ZO-1 were measured by immunofluorescence method. We searched for 7 HIF-1α hypoxia response elements within 4000 bp before the transcription start site in the MMP-9 promoter region, constructed the MMP-9 promoter-luciferase reporter gene recombinant plasmid, transfected and stimulated HUVEC with TNFα, and detected the effect of 7 hypoxia response element plasmids on the transcription activity of MMP-9 promoter. RESULTS: Under the action of TNFα, the permeability of monolayer endothelial cells increased, and the concentration of MMP-9 in the cell supernatant increased. 2ME2 and HIF-1α-siRNA transfection can improve the above situation (P < 0.05). 2ME2 and HIF-1α-siRNA transfection can inhibit the high expression of HIF-1α and MMP-9 caused by TNFα, thereby increasing the expression of claudin-5 and ZO-1 (P < 0.05). 2ME2 and HIF-1α-siRNA transfection can reduce the inhibition of TNFα on the expression of cell membrane protein claudin-5 and tight junction protein ZO-1. Element 1, element 5, and element 7 are the sites where HIF-1α interacts with MMP-9 at the transcription level. CONCLUSION: This study shows that HIF-1α can increase the permeability of monolayer epithelial cells by inducing the high expression of MMP-9, leading to capillary leakage. Its target is at the -3798 bp, -1878 bp, and -1489 bp points of the transcription initiation site in the MMP-9 promoter region.

A Helmholtz resonator on elastic foundation for measurement of the elastic coefficient of human skin.

A new sensing mechanism is proposed for the measurement of elasticity of human skin by utilizing Helmholtz resonator with a flexible membrane mounted at the bottom and putting on an elastic foundation. Elastic coefficient of human skin is modeled as the elastic foundation modulus, based on the assumption that human skin is equivalent to the Winkler foundation. For the Helmholtz resonator, the acoustic transmission loss (by which resonant frequency can be acquired) was derived by using the receptance coupling method, based on the theories of conventional Helmholtz resonator and fixed-edge membrane on elastic foundation. The fundamental resonant frequency of the proposed Helmholtz resonator was proved to be related with the elastic foundation modulus, and was used as the indicator of elastic foundation modulus to be measured. Theoretical derivation for measuring elastic foundation modulus and analytical example were presented. Experiments measuring the elastic foundation modulus of the phantoms were carried out by utilizing phantoms with different stiffness using gelatin with corresponding different concentrations. The analytical and experimental results verified the effectiveness of the proposed method. Nanoindentation test was conducted for comparison, and relative errors ranged from 9.24% to 20.06% were obtained, which tends to be higher with the increasing concentration of gelatin.

Benzothiazines in synthesis. A formal total synthesis of pseudopteroxazole.

A formal total synthesis of the antitubercular natural product was accomplished. This work was undertaken to address certain stereochemical problems in our initial synthesis. By using an ester group as a surrogate for a methyl group, we were able to intercept a key intermediate in our first synthesis with better selectivity and greater convergence than had previously been the case.

Arseniasis prevalence and mortality in a multiethnic, endemic township in Guizhou, China.

OBJECTIVE: Farmers in Southwest Guizhou Autonomous Prefecture, China, represent a unique case of arseniasis, which is related to indoor combustion of high arsenic-containing coal instead of to arsenic-contaminated drinking water. A significant difference in the prevalence of arseniasis was observed in two neighboring ethnic clans in one village. The question arose whether the ethnicity-dependent difference observed in this village was more widely spread throughout the whole township. An epidemiologic investigation was designed to explore arseniasis distribution and mortality among all four ethnic groups in a multiethnic township. METHODS: The cohort of arseniasis patients, diagnosed and registered in the overall field survey of 1991 as well as all the asymptomatic residents of the township, were enrolled in the present investigation. Indirect standardization was used for calculating the age-adjusted standardized incidence ratio (SIR) of arseniasis, the standardized mortality ratio (SMR) of various death causes (including some cancers), and their corresponding intervals of 95% confidence in both genders and in each local ethnic group. RESULTS: The descending rank of arseniasis SIRs among local ethnic groups was found as: Hui>Han>Bouyei>Hmong. The descending rank of SMRs of malignancies was displayed as: Han>Hui>Bouyei>Hmong in males and both genders together as well. Concerning deaths of non-malignant causes the rank was observed as: Hui>Han>Bouyei>Hmong in males. The arseniasis SIR for ethnic Hmong residents (both genders combined) was found to be significantly less profound than the overall level in the township. No death cases in diagnosed ethnic Hmong patients and no cases of death from malignant causes in asymptomatic Hmong residents were recorded. The significant increase of arseniasis prevalence was observed in all males, compared with the overall prevalence of all residents. However, a significantly lower prevalence was seen in all females. CONCLUSION: Significant ethnicity-dependent difference in arseniasis prevalence and mortality from all causes was found in a multiethnic rural township where farmers have been exposed to the indoor combustion of high arsenic coal for decades. The ethnic Hmong residents seemed to be the least susceptible to arseniasis among the four local ethnic groups.

The simplest construction of single-site catalysts by the synergism of micropore trapping and nitrogen anchoring.

Single-site catalysts feature high catalytic activity but their facile construction and durable utilization are highly challenging. Herein, we report a simple impregnation-adsorption method to construct platinum single-site catalysts by synergic micropore trapping and nitrogen anchoring on hierarchical nitrogen-doped carbon nanocages. The optimal catalyst exhibits a record-high electrocatalytic hydrogen evolution performance with low overpotential, high mass activity and long stability, much superior to the platinum-based catalysts to date. Theoretical simulations and experiments reveal that the micropores with edge-nitrogen-dopants favor the formation of isolated platinum atoms by the micropore trapping and nitrogen anchoring of [PtCl6]2-, followed by the spontaneous dechlorination. The platinum-nitrogen bonds are more stable than the platinum-carbon ones in the presence of adsorbed hydrogen atoms, leading to the superior hydrogen evolution stability of platinum single-atoms on nitrogen-doped carbon. This method has been successfully applied to construct the single-site catalysts of other precious metals such as palladium, gold and iridium.

Benzothiazines in organic synthesis. Stereoselectivity in the intermolecular Michael addition reactions of benzothiazines.

A study of the intermolecular Michael addition of certain benzothiazine anions demonstrated that stereoselectivity could be extremely high, though achieving control over the direction of relative stereoselectivity was in general not straightforward.

Photochemical cyclization with release of carboxylic acids and phenol from pyrrolidino-substituted 1,4-benzoquinones using visible light.

Visible light irradiation of 5-acyloxymethyl- and 5-phenoxymethyl-2-pyrrolidino-1,4-benzoquinones effects photoisomerization to labile oxazolidines, which undergo elimination of carboxylate or phenolate leaving groups in high yields to generate trappable o-quinone methide intermediates. [reaction: see text]

The monoacylglycerol lipase inhibitor JZL184 suppresses inflammatory pain in the mouse carrageenan model.

AIM: The present study tested whether the selective monoacylglycerol lipase (MAGL) inhibitor JZL184 would reduce allodynia and paw edema in the carrageenan test. MAIN METHODS: The anti-edematous and anti-allodynic effects of JZL184 were compared to those of PF-3845, an inhibitor of fatty acid amide hydrolase (FAAH), and diclofenac, a non-selective cyclooxygenase inhibitor. Cannabinoid receptor involvement in the anti-edematous and anti-allodynic effects of JZL184 was evaluated by administration of the respective CB1 and CB2 receptor antagonists rimonabant and SR144528 as well as with CB1(-/-) and CB2(-/-) mice. JZL184 (1.6, 4, 16, or 40mg/kg) was administered for six days to assess tolerance. KEY FINDINGS: JZL184 administered before or after carrageenan significantly attenuated carrageenan-induced paw edema and mechanical allodynia. Complementary genetic and pharmacological approaches revealed that the anti-allodynic effects of JZL184 required both CB1 and CB2 receptors, but only CB2 receptors mediated its anti-edematous actions. Importantly, both the anti-edematous and anti-allodynic effects underwent tolerance following repeated injections of high dose JZL184 (16 or 40mg/kg), but repeated administration of low dose JZL184 (4mg/kg) retained efficacy. SIGNIFICANCE: These results suggest that the MAGL inhibitor JZL184 reduces inflammatory nociception through the activation of both CB1 and CB2 receptors, with no evidence of tolerance following repeated administration of low doses.

A novel fluorophosphonate inhibitor of the biosynthesis of the endocannabinoid 2-arachidonoylglycerol with potential anti-obesity effects.

BACKGROUND AND PURPOSE: The development of potent and selective inhibitors of the biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG) via DAG lipases (DAGL) α and ß is just starting to be considered as a novel and promising source of pharmaceuticals for the treatment of disorders that might benefit from a reduction in endocannabinoid tone, such as hyperphagia in obese subjects. EXPERIMENTAL APPROACH: Three new fluorophosphonate compounds O-7458, O-7459 and O-7460 were synthesized and characterized in various enzymatic assays. The effects of O-7460 on high-fat diet intake were tested in mice. KEY RESULTS: Of the new compounds, O-7460 exhibited the highest potency (IC50 = 690 nM) against the human recombinant DAGLα, and selectivity (IC50 > 10 µM) towards COS-7 cell and human monoacylglycerol lipase (MAGL), and rat brain fatty acid amide hydrolase. Competitive activity-based protein profiling confirmed that O-7460 inhibits mouse brain MAGL only at concentrations ≥ 10 µM, and showed that this compound has only one major 'off-target', that is, the serine hydrolase KIAA1363. O-7460 did not exhibit measurable affinity for human recombinant CB1 or CB2 cannabinoid receptors (Ki > 10 µM). In mouse neuroblastoma N18TG2 cells stimulated with ionomycin, O-7460 (10 µM) reduced 2-AG levels. When administered to mice, O-7460 dose-dependently (0-12 mg·kg⁻¹, i.p.) inhibited the intake of a high-fat diet over a 14 h observation period, and, subsequently, slightly but significantly reduced body weight. CONCLUSIONS AND IMPLICATIONS: O-7460 might be considered a useful pharmacological tool to investigate further the role played by 2-AG both in vitro and in vivo under physiological as well as pathological conditions.

[Clinical application of the scapular free flap extended to the upper arm].

OBJECTIVE: To apply the scapular free flap extended to the upper arm for resurfacing the face and neck, as well as the upper lip in one stage. METHODS: The scapular free flap was designed with extended portion to the posterior and interior part of the upper arm. Then the free flap was transferred to resurface the face and neck with the routine portion and to resurface the upper lip with the extended portion. RESULTS: 6 cases with extensive upper lip, facial and cervical burn scar were treated with the extended scapular free flaps. The flap size ranged from 22 cm x 11 cm to 40 cm x 9.5 cm (36.57 cm x 10.20 cm in average) for the routine portion and from 7 cm x 4 cm to 12 cm x 4 cm (10.32 cm x 3.67 cm in average) for the extended portion. All flaps survived completely. CONCLUSIONS: There are direct communicating branches ("choke vessel") between the circumflex scapular artery (CSA) and the posterior humeral circumflex artery (PHCA). When the blood supply of PHCA is cut off, the CSA can provide blood supply through the communicating branches to the upper arm skin area previously nourished by PHCA. So the blood supply of the extended portion of the scapular free flap is not only from the branches of CSA, but also from the direct communicating branches between the CSA and PHCA. The extended scapular free flap has a reliable blood supply and can be applied to construct the facial and cervical scar contraction with the extended portion to resurface the upper lip. The satisfactory result can be expected.

[Repair of the facial defects using the expanded induced prefabricated skin flap of the retroauricular and mastoid process region based on the superficial temporal vascular bundle].

OBJECTIVE: To provide an ideal method for flap prefabrication. METHODS: The superficial temporal fascial flap has been elevated based on the superficial temporal vessels during the first-stage procedure. A subcutaneous tissue pocket with appropriate site was formed in the retroauricular and mastoid process region. The fascial flap was transferred into the pocket and fixed properly. The tissue expander was placed under the fascial flap. When the expanding process has been finished, the expander was removed and the expanded induced prefabricated skin flap of the retroauricular and mastoid process region pedicled on the superficial temporal vascular bundle was elevated and transferred to repair the facial skin defect. RESULTS: There were nine cases in the group. Facial defects after resection of the melanotic nevus was repaired in 2 cases and facial defects after resection of the facial haemangioma and scar were repaired in 2 and 5 cases respectively. Pedicle length of the superficial temporal fascial flap was ranged from 5.5 cm to 7 cm (mean length 6.2 cm). The size of the fascial flaps was ranged from 4 cm x 3 cm to 7 cm x 7 cm (mean size 5.7 cm x 4.9 cm). The size of the prefabricated skin flaps was ranged from 5 cm x 5 cm to 8.0 cm x 7.5 cm (mean size 6.4 cm x 6.1 cm). The average time of the tissue expansion process is 16.1 weeks. All flaps survived postoperatively and the donor sites of the flaps were appropriated directly in 5 cases. The split-thickness skin grafting was used to recover the donor site defects in 4 cases. CONCLUSIONS: The superficial temporal fascial flap owns the following advantages: the vascular pedicle is much longer and vascular supply is plentiful, and it is convenient to transfer. Meanwhile, the skin of the retroauricular and mastoid process region is most similar to that of the face in texture, color and depth. For the patients selected strictly, the technique mentioned above is somewhat an ideal method for facial defect repair.

A follow-up study of mortality among the arseniasis patients exposed to indoor combustion of high arsenic coal in Southwest Guizhou Autonomous Prefecture, China.

OBJECTIVE: This study was directed to ascertain the mortality of a group of arseniasis patients in an endemic rural township in Southwest China, where the residents were exposed for decades to indoor combustion of high arsenic coal. METHODS: All the diagnosed arseniasis cases registered in 1991 were defined as the target population, which were assigned to three symptom subgroups by the severity of dermal lesions. The death cases were surveyed and checked. The follow-up period was 12.5 years. The standardized mortality ratio (SMR) of all death causes combined, all cancers combined, and the cancers at every site were analyzed. The age standardized mortality rates (ASMRs) were calculated in three subgroups using the procedure of standardization. RESULTS: One hundred and six death cases were recorded. Liver cirrhosis, non-melanotic skin cancer, lung and liver cancer were the four most prevalent death causes and referred to 70.8% (75/106) of the total death cases. The mortality of all death causes combined was not higher than that of the whole of China in 2001 (SMR = 0.76, 95% CI 0.63-0.93). The crude mortality rate of non-melanotic skin cancer in males reached up to 128.66/10(5). SMRs of lung cancer and larynx cancer in males (SMRs 2.84 and 27.27, 95% CIs 1.51-4.86 and 5.61-79.62, respectively) significantly exceeded the levels for all male Chinese. ASMRs of all death causes combined, all cancers combined and non-melanotic skin cancer in males of the severe dermal symptoms subgroup were significantly higher than those in medium and/or mild dermal symptom subgroups. CONCLUSIONS: A significantly increased mortality due to lung cancer and non-melanotic skin cancer was confirmed, alike the situation in other arseniasis endemic areas in the world. No significant elevation of mortality due to liver cancer and bladder cancer was observed. Male arseniasis patients diagnosed with severe skin lesions face higher risks of malignancies and of non-melanotic skin cancer in particular in the following years.

Photoactivation of amino-substituted 1,4-benzoquinones for release of carboxylate and phenolate leaving groups using visible light.

Upon exposure to visible light, 2-pyrrolidino-substituted 3,6-dimethyl-1,4-benzoquinones photocyclize to give benzoxazolines with quantum yields of 0.07-0.10 in CH2Cl2, 0.02-0.04 in CH3CN, and <0.01 in 30% aq CH3CN. With carboxylate or phenolate leaving groups incorporated via coupling to a 5-hydroxymethyl group of the quinones, the photocyclizations give benzoxazolines that eliminate the leaving groups in a dark reaction. Lifetimes for elimination of 4-YC6H4OH in 30% phosphate buffer in CD3CN (pD 7) at 17 degrees C are 13.1, 0.54, and 0.13 h for Y = H, CF3, and CN, respectively, and the linear equation log k (h(-1)) = 0.998(-pKa) + 8.80 gives a best fit to the data. Carboxylate leaving groups are rapidly eliminated upon photolysis of the quinones in aq CH3CN to produce an o-quinone methide intermediate that is trapped by 4 + 2 cycloaddition with unreacted starting material or with added 3-(dimethylamino)-5,5-dimethyl-2-cyclohexen-1-one. The ortho-quinone methide is observed at 339 and 455 nm by conventional absorption spectroscopy and gives a pseudo-first-order fit of the decay kinetics with tau1/2 = 34.9 min in 30% phosphate buffer in CH3CN at 20 degrees C.

Photochemical cleavage and release of para-substituted phenols from alpha-keto amides.

In aqueous media alpha-keto amides 4-YC6H4OCH2COCON(R)CH(R')CH3 (5a, R = Et, R' = H; 5b, R = iPr, R' = Me) with para-substituted phenolic substituents (Y = CN, CF3, H) undergo photocleavage and release of 4-YC6H4OH with formation of 5-methyleneoxazolidin-4-ones 7a,b. For both 5a,b quantum yields range from 0.2 to 0.3. The proposed mechanism involves transfer of hydrogen from an N-alkyl group to the keto oxygen to produce zwitterionic intermediates 8a-c that eliminate the para-substituted phenolate leaving groups. The resultant imminium ions H2C=C(OH)CON+(R)=C(R')CH3 9a,b cyclize intramolecularly to give 7a,b. The quantum yields for photoelimination decrease in CH3CN, CH2Cl2, or C6H6 due to competing cyclization of 8a,b to give oxazolidin-4-one products which retain the leaving group 4-YC6H4O- (Y = H, CN). A greater tendency to undergo cyclization in nonaqueous media is observed for the N,N-diethyl amides 5a than the N,N-diisopropyl amides 5b. With para electron releasing groups Y = CH3 and OCH3 quantum yields for photoelimination significantly decrease and 1,3-photorearrangment of the phenolic group is observed. The 1,3-rearrangement involves excited state ArO-C bond homolysis to give para-substituted phenoxyl radicals, which can be observed directly in laser flash photolysis experiments.