Intensive Ambulance-Delivered Blood-Pressure Reduction in Hyperacute Stroke.

BACKGROUND: Treatment of acute stroke, before a distinction can be made between ischemic and hemorrhagic types, is challenging. Whether very early blood-pressure control in the ambulance improves outcomes among patients with undifferentiated acute stroke is uncertain. METHODS: We randomly assigned patients with suspected acute stroke that caused a motor deficit and with elevated systolic blood pressure (≥150 mm Hg), who were assessed in the ambulance within 2 hours after the onset of symptoms, to receive immediate treatment to lower the systolic blood pressure (target range, 130 to 140 mm Hg) (intervention group) or usual blood-pressure management (usual-care group). The primary efficacy outcome was functional status as assessed by the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days after randomization. The primary safety outcome was any serious adverse event. RESULTS: A total of 2404 patients (mean age, 70 years) in China underwent randomization and provided consent for the trial: 1205 in the intervention group and 1199 in the usual-care group. The median time between symptom onset and randomization was 61 minutes (interquartile range, 41 to 93), and the mean blood pressure at randomization was 178/98 mm Hg. Stroke was subsequently confirmed by imaging in 2240 patients, of whom 1041 (46.5%) had a hemorrhagic stroke. At the time of patients' arrival at the hospital, the mean systolic blood pressure in the intervention group was 159 mm Hg, as compared with 170 mm Hg in the usual-care group. Overall, there was no difference in functional outcome between the two groups (common odds ratio, 1.00; 95% confidence interval [CI], 0.87 to 1.15), and the incidence of serious adverse events was similar in the two groups. Prehospital reduction of blood pressure was associated with a decrease in the odds of a poor functional outcome among patients with hemorrhagic stroke (common odds ratio, 0.75; 95% CI, 0.60 to 0.92) but an increase among patients with cerebral ischemia (common odds ratio, 1.30; 95% CI, 1.06 to 1.60). CONCLUSIONS: In this trial, prehospital blood-pressure reduction did not improve functional outcomes in a cohort of patients with undifferentiated acute stroke, of whom 46.5% subsequently received a diagnosis of hemorrhagic stroke. (Funded by the National Health and Medical Research Council of Australia and others; INTERACT4 ClinicalTrials.gov number, NCT03790800; Chinese Trial Registry number, ChiCTR1900020534.).

Island-Like Heterogeneous Interface Generating Tandem Toroidal Built-In Electric Field for Efficient Potassium Ions Diffusion.

For large-size potassium accommodation, heterostructure usually suffers severe delamination and exfoliation at the interfaces due to different volume expansion of two-phase during charge/discharge process, resulting in the deconstruction of heterostructures and shortened lifespan of batteries. Here, an innovative strategy is proposed through constructing a microscopic heterostructure system containing copper quantum dots (Cu QDs) highly dispersed in the triphenyl-substituted triazine graphdiyne (TPTG) substrates (TPTG@CuQDs) to solve this problem. The copper quantum dots are uniformly anchored on TPTG substrates, generating a myriad of island-like heterogeneous structures, together with tandem toroidal built-in electric field (BIEF) between every micro heterointerface. The island-like heterostructure endows both benefits of exposed contact interface and robust architecture. Generated tandem toroidal BIEF provides efficient transport pathways with lower energy barriers, reducing the diffusion resistance and facilitating the reaction kinetics of potassium ions. When used as anode, the TPTG@CuQDs exhibit highly reversible capacity and low-capacity degradation (≈0.01% over 5560 cycles at 1 A g-1). Moreover, the TPTG@CuQDs-based full cell delivers an outstanding reversible capacity of ≈110 mAh g-1 over 800 cycles at 1 A g-1. This quantum-scale heterointerface construction strategy offers a new approach toward stable heterostructure design for the application of metal ion batteries.

3D Covalent Organic Framework Membranes for Molecular Separations.

Membrane separation has become an indispensable separation technology in social production, playing an important role in drug production, water purification, etc. The key core of membranes lies in achieving efficient and precise sieving between substances. As a result, a typical trade-off arises: highly permeable membranes usually sacrifice selectivity and vice versa. To address this dilemma, long-term research has focused on comprehensive understanding and modelling of synthetic membranes at various scales. A significant advancement in this arena is the advent of three-dimensional covalent organic framework (3D COF) membranes, a novel category of long-range ordered porous organic polymer materials. Characterized by an abundance of interconnected channels, diverse pore wall properties, tunable structures, and robust thermal and chemical resilience, 3D COF membranes offer a promising approach for efficient substance separation. This review undertakes a meticulous investigation of the synthesis and physicochemical properties of 3D COF membranes, accentuating the underlying design principles, fabrication methods, and application attempts. A comprehensive assessment of their research trajectory and current standing in the field of membrane processes is provided. The review culminates in a forward-looking outlook, summarizing future research directions and highlighting the substantial potential of this innovative work to shape the future of efficient membrane separation processes.

A new mode for the diagnosis of angioimmunoblastic T-cell lymphoma.

In order to explore a new mode for the diagnosis of angioimmunoblastic T-cell lymphoma (AITL), 31 cases of AITL and 28 cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) were used as the study subjects. Identifying T follicular helper (TFH) cells with CD4, CD10, Bcl-6, and PD-1, identifying proliferative B cells with CD20 and EZH2, identifying proliferative follicular dendritic cells (FDCs) with CD21 and CD23, and analyzing the value of TFH/B/FDC proliferation and immunolocalization in the diagnosis of AITL. (1) Outside the inherent lymphoid follicles, simultaneous proliferation of TFH/B/FDC (a new diagnostic mode) were observed in AITL [83.87%; 26/31], with their immunolocalizations in the same site [83.87%; 26/31], while this phenomenon was not observed in 28 cases of PTCL-NOS (P<0.05). (2) The sensitivity and specificity of using this new mode to diagnose AITL were both high (83.87%, 100%), which was superior to CD2 (100%, 0%), CD3 (100%, 0%), CD4 (100%, 32.14%), CD5 (100%, 25%), CD10 (61.9%, 100%), Bcl-6 (42.86%, 100%), PD-1 (83.87%, 96.43%), and its Youden Index (0.84) was the highest. The areas under the curve (AUC) of CD10, Bcl-6, PD-1, and new mode to diagnosis AITL were 0.81, 0.71, 0.90, and 0.92, respectively, while the new mode had the highest AUC. The simultaneous proliferation of TFH/B/FDC cells outside the inherent lymphoid follicles can be used to assist in the diagnosis of AITL, and the simultaneous spatiotemporal proliferation of TFH/B/FDC cells is a specific immunomorphology of AITL.

Scalable Preparation of Ultraselective and Highly Permeable Fully Aromatic Polyamide Nanofiltration Membranes for Antibiotic Desalination.

Membranes are important in the pharmaceutical industry for the separation of antibiotics and salts. However, its widespread adoption has been hindered by limited control of the membrane microstructure (pore architecture and free-volume elements), separation threshold, scalability, and operational stability. In this study, 4,4',4'',4'''-methanetetrayltetrakis(benzene-1,2-diamine) (MTLB) as prepared as a molecular building block for fabricating thin-film composite membranes (TFCMs) via interfacial polymerization. The relatively large molecular size and rigid molecular structure of MTLB, along with its non-coplanar and distorted conformation, produced thin and defect-free selective layers (~27 nm) with ideal microporosities for antibiotic desalination. These structural advantages yielded an unprecedented high performance with a water permeance of 45.2 L m-2 h-1 bar-1 and efficient antibiotic desalination (NaCl/adriamycin selectivity of 422). We demonstrated the feasibility of the industrial scaling of the membrane into a spiral-wound module (with an effective area of 2.0 m2). This module exhibited long-term stability and performance that surpassed those of state-of-the-art membranes used for antibiotic desalination. This study provides a scientific reference for the development of high-performance TFCMs for water purification and desalination in the pharmaceutical industry.

One-Pot Stereoselective Synthesis of Furantetrahydroquinoline Derivatives Using d/l-Ribose with a 2,3-O-Isopropylidene Group.

An efficient and convenient strategy has been successfully developed for the preparation of novel furantetrahydroquinoline derivatives using d/l-ribose with a 2,3-O-isopropylidene group through the aza-Diels-Alder mechanism. This method has high atom and step economy, high stereoselectivity, and gram-scale synthesis (yield 67%).

Marine Dehalogenator and Its Chaperones: Microbial Duties and Responses in 2,4,6-Trichlorophenol Dechlorination.

Marine environments contain diverse halogenated organic compounds (HOCs), both anthropogenic and natural, nourishing a group of versatile organohalide-respiring bacteria (OHRB). Here, we identified a novel OHRB (Peptococcaceae DCH) with conserved motifs but phylogenetically diverse reductive dehalogenase catalytic subunit (RdhAs) from marine enrichment culture. Further analyses clearly demonstrate the horizontal gene transfer of rdhAs among marine OHRB. Moreover, 2,4,6-trichlorophenol (TCP) was dechlorinated to 2,4-dichlorophenol and terminated at 4-chlorophenol in culture. Dendrosporobacter and Methanosarcina were the two dominant genera, and the constructed and verified metabolic pathways clearly demonstrated that the former provided various substrates for other microbes, while the latter drew nutrients, but might provide little benefit to microbial dehalogenation. Furthermore, Dendrosporobacter could readily adapt to TCP, and sporulation-related proteins of Dendrosporobacter were significantly upregulated in TCP-free controls, whereas other microbes (e.g., Methanosarcina and Aminivibrio) became more active, providing insights into how HOCs shape microbial communities. Additionally, sulfate could affect the dechlorination of Peptococcaceae DCH, but not debromination. Considering their electron accessibility and energy generation, the results clearly demonstrate that bromophenols are more suitable than chlorophenols for the enrichment of OHRB in marine environments. This study will greatly enhance our understanding of marine OHRB (rdhAs), auxiliary microbes, and microbial HOC adaptive mechanisms.

Synergistic Modulation by Halogens and Pyridine Crossing the Blood-Brain Barrier for In Situ Visualization of Thiol Flux in the Epileptic Brain.

Epilepsy is a nervous system disease, and seizures are closely related to oxidative stress. Thiols, as the main antioxidant in an organism, play a key role in regulating the redox balance and defending from oxidative stress. As a result of the complexity of the brain structure, there is still a lack of suitable in situ detection methods of thiols to reveal the relationship between epilepsy and thiol level fluctuations. Therefore, by combining picolinate as the new recognition site for thiols, parallel synthesis, and the fluorescence rapid screening method, DCI-Br-3 was developed as a rapid, highly sensitive, and selective probe to monitor thiols in vitro and in vivo. It is worth noting that DCI-Br-3 effectively crossed the blood-brain barrier (BBB) to reveal the negative relationship between the level of thiols and the occurrence of epilepsy and may further provide important information for the prevention and treatment of thiol-related neurological diseases.

Plasma tRNA-derived small RNAs signature as a predictive and prognostic biomarker in lung adenocarcinoma.

BACKGROUND: The prevalence of lung adenocarcinoma (LUAD) has increased, thus novel biomarkers for its early diagnosis is becoming more important than ever. tRNA-derived small RNA (tsRNA) is a new class of non-coding RNA which has important regulatory roles in cancer biology. This study was designed to identify novel predictive and prognostic tsRNA biomarkers. METHODS: tsRNAs were identified and performed differential expression analysis from 10 plasma samples (6 LUAD and 4 normal, SRP266333) and 96 tissue samples (48 LUAD and 48 normal, SRP133217). Then a tsRNA-mRNA regulatory network was constructed to find hub tsRNAs. Functional enrichment analysis was performed to infer the potential pathways associated with tsRNAs. Afterwards, a Support Vector Machine (SVM) algorithm was used to explore the potential biomarkers for diagnosing LUAD. Lastly, the function of tRF-21-RK9P4P9L0 was explored in A549 and H1299 cell lines. RESULTS: A significant difference of read distribution was observed between normal people and LUAD patients whether in plasma or tissue. A tsRNA-mRNA regulatory network consisting of 155 DEtsRNAs (differential expression tsRNAs) and 406 DEmRNAs (differential expression mRNAs) was established. Three tsRNAs (tRF-16-L85J3KE, tRF-21-RK9P4P9L0 and tRF-16-PSQP4PE) were identified as hub genes with degree > 100. We found Co-DEmRNAs (intersection of DEtsRNAs target mRNAs and differentially expressed mRNAs in LUAD) were engaged in a number of cancer pathways. The AUC of the three hub tsRNAs' expression for diagnosing LUAD reached 0.92. Furthermore, the qPCR validation of the three hub tsRNAs in 37 paired normal and LUAD tissues was consistent with the RNA-Seq results. In addition, tRF-21-RK9P4P9L0 was negatively associated with LUAD prognosis. Inhibition of tRF-21-RK9P4P9L0 expression reduced the proliferation, migration and invasion ability of A549 and H1299 cell lines. CONCLUSION: These findings will help us further understand the molecular mechanisms of LUAD and contribute to novel diagnostic biomarkers and therapeutic target discovery.

Offshore Marine Sediment Microbiota Respire Structurally Distinct Organohalide Pollutants.

Marine sediments are a major sink of organohalide pollutants, but the potential for offshore marine microbiota to transform these pollutants remains underexplored. Here, we report dehalogenation of diverse organohalide pollutants by offshore marine microbiota. Dechlorination of polychlorinated biphenyls (PCBs) was observed in four marine sediment microcosms, which was positively correlated with in situ PCB contamination. Three distinct enrichment cultures were enriched from these PCB-dechlorinating microcosms using tetrachloroethene (PCE) as the sole organohalide. All enrichment cultures also dehalogenated polybrominated diphenyl ethers (PBDEs), tetrabromobisphenol A (TBBPA), and 2,4,6-trichlorophenol (2,4,6-TCP). Particularly, two enrichments completely debrominated penta-BDEs, the first observation of complete debromination of penta-BDEs in marine cultures. Multiple Dehalococcoides and uncultivated Dehalococcoidia were identified in the initial sediment microcosms, but only Dehalococcoides was dominant in all enrichments. Transcription of a gene encoding a PcbA5-like reductive dehalogenase (RDase) was observed during dehalogenation of different organohalides in each enrichment culture. When induced by a single organohalide substrate, the PcbA5-like RDase dehalogenated all tested organohalides (PCE, PCBs, PBDEs, TBBPA, and 2,4,6-TCP) in in vitro tests, suggesting its involvement in dehalogenation of structurally distinct organohalides. Our results demonstrate the versatile dehalogenation capacity of marine Dehalococcoidia and contribute to a better understanding of the fate of these pollutants in marine systems.

GRP78 facilitates M2 macrophage polarization and tumour progression.

This study investigated the regulation of GRP78 in tumour-associated macrophage polarization in lung cancer. First, our results showed that GRP78 was upregulated in macrophages during M2 polarization and in a conditioned medium derived from lung cancer cells. Next, we found that knocking down GRP78 in macrophages promoted M1 differentiation and suppressed M2 polarization via the Janus kinase/signal transducer and activator of transcription signalling. Moreover, conditioned medium from GRP78- or insulin-like growth factor 1-knockdown macrophages attenuated the survival, proliferation, and migration of lung cancer cells, while conditioned medium from GRP78-overexpressing macrophages had the opposite effects. Additionally, GRP78 knockdown reduced both the secretion of insulin-like growth factor 1 and the phosphorylation of the insulin-like growth factor 1 receptor. Interestingly, insulin-like growth factor 1 neutralization downregulated GRP78 and suppressed GRP78 overexpression-induced M2 polarization. Mechanistically, insulin-like growth factor 1 treatment induced the translocation of GRP78 to the plasma membrane and promoted its association with the insulin-like growth factor 1 receptor. Finally, IGF-1 blockade and knockdown as well as GRP78 knockdown in macrophages inhibited M2 macrophage-induced survival, proliferation, and migration of lung cancer cells both in vitro and in vivo.

Investigation of Factors Influencing the Fear of Cancer Recurrence in Breast Cancer Patients Using Structural Equation Modeling: A Cross-Sectional Study.

Objective: This study aimed to investigate the fear of cancer recurrence (FCR) in breast cancer patients and develop a structural equation model of influencing factors to help formulate clinical intervention strategies. Methods: A convenience sample of 325 patients was surveyed using a general and disease-related data questionnaire, which combined the Fear of Progression Questionnaire-Short Form, Mishel Uncertainty in Illness Scale, Perceived Social Support Scale, and Medical Coping Modes Questionnaire. Results: The total score of FCR in breast cancer patients was 35.06 ± 10.83, and 53.8% of patients reached the clinical level. The structural equation model demonstrated that illness uncertainty had a direct positive impact on FCR (ß = 0.275, p < 0.05), and it could have an indirect impact through social support and resignation coping methods (ß = 0.254, p < 0.05). Conclusion: The fear of cancer recurrence in breast cancer patients needs further understanding. Medical staff can reduce or buffer FCR in breast cancer patients by strengthening positive influences, such as social support, or weakening negative influences, such as illness uncertainty and resignation coping.

A biosurfactant-producing yeast Rhodotorula sp.CC01 utilizing landfill leachate as nitrogen source and its broad degradation spectra of petroleum hydrocarbons.

Biosurfactants (BSs) are known for their remarkable properties, however, their commercial applications are hampered partly by the high production cost. To overcome this issue, a biosurfactant producing strain, Rhodotorula sp.CC01 was isolated using landfill leachate as nitrogen source, while olive oil was determined as the best sole carbon source. The BS produced by Rhodotorula sp.CC01 had oil displacement diameter of 19.90 ± 0.10 cm and could reduce the surface tension of water to 34.77 ± 0.63 mN/m. It was characterized as glycolipids by thin layer chromatography, FTIR spectra, and GC-MS analysis, with the critical micelle concentration of 70 mg/L. Meanwhile, the BS showed stability over a wide range of pH (2-12), salinity (0-100 g/L), and temperature (20-100 °C). During the cultivation process, BS was produced with a maximum rate of 163.33 mg L-1 h-1 and a maximum yield of 1360 mg/L at 50 h. In addition, the removal efficiency of NH4+-N reached 84.2% after 75 h cultivation with a maximum NH4+-N removal rate of 3.92 mg L-1 h-1. Moreover, Rhodotorula sp.CC01 has proven to be of great potential in remediating petroleum hydrocarbons, as revealed by chromogenic assays. Furthermore, genes related to nitrogen metabolism and glycolipid metabolism were found in this strain CC01 after annotating the genome data with KEGG database, such as narB, glycoprotein glucosyltransferase, acetyl-CoA C-acetyltransferase, LRA1, LRA3, and LRA4. The findings of this study prove a cost-effective strategy for the production of BS by yeast through the utilization of landfill leachate.

[Safety and feasibility of robotic-assisted thoracoscopic day surgery for pulmonary nodules: a retrospective analysis based on propensity score matching].

Objective: To evaluate the safety and feasibility of robotic-assisted thoracoscopic day surgery for pulmonary nodules. Methods: Clinical data of 523 patients with pulmonary nodule underwent robotic-assisted thoracoscopic surgery in the Department of Thoracic Surgery, Xiangya Hospital, Central South University from January 2021 to June 2022 were retrospectively analyzed, which including 223 males and 300 females, aged from 19 to 72 (54.0±11.7) years. Those patients were divided into the day surgery group (DSG) and inpatient surgery group (ISG) according to perioperative management methods. Propensity score matching (PSM) (1∶2) was performed according to the general baseline information, T stage of the tumor, surgery approach, and tumor position, and a total of 178 patients were finally included. Clinical outcomes of DSG were observed. The differences in incidence of postoperative complications, treatment-related costs and resource consumption between DSG and ISG were compared. Subgroup analysis was performed according to surgery method to evaluate the difference between DSG and ISG in lobectomy and sublobectomy. Results: In 81 cases DSG, eight patients were transferred to thoracic surgery ward, and the day surgery discharge rate was 90% (73/81). There was no statistically significant difference in incidence of postoperative complications between DSG and ISG (P=0.612). The length of stay after surgery, period of chest draining, average hospital cost, and drug cost of DSG were statistically significant lower than ISG, ((2.19±0.84) vs (4.74±1.81) days, (1.70±0.65) vs (3.45±1.85) days, (6.64±0.74) vs (8.29±0.97)×104 CNY, (0.35±0.07) vs (0.69±0.18)×104 CNY), respectively(all P<0.05). The drainage volume and VAS score at discharge in DSG and ISG group were(220.47±120.02) ml and(242.21±129.96) ml, 1.68±0.79 and 1.64±0.91, respectively, with no statistically significant difference (P>0.05). In subgroup analysis, there was no statistically significant difference in incidence of postoperative complications, drainage volume after surgery and VAS score at discharge between DSG and ISG both for lobectomy and sublobectomy patients. And the results of the length of stay after surgery, period of chest draining, and drug cost in DSG were also significantly lower than ISG (P<0.05). Conclusions: Robotic-assisted thoracoscopic day surgery for pulmonary nodule is safe and feasible, with the advantage of short length of stay after surgery, short period of chest draining, less average hospital cost and drug cost. There is no difference in incidence of postoperative complications between DSG and ISG.

Pentagon-Containing π-Expanded Systems: Synthesis and Photophysical Properties.

We have designed and synthesized three novel twistacene-modified enlarged pentagon-containing π-systems (6 and 9) with mismatched structures. The introduction of electron-withdrawing cyclopenta rings in the parent skeleton effectively stabilizes the electron-rich arenes. Their optoelectronic properties were studied via ultraviolet-visible (UV-vis) absorption spectra, fluorescence spectra, cyclic voltammetry, and density functional theory (DFT) calculation. In addition, chemical oxidation of the as-prepared compounds with nitrosonium hexafluoroantimonate could form the corresponding cationic radicals.

Double π-Extended Helicene Derivatives Containing Pentagonal Rings: Synthesis, Crystal Analyses, and Photophysics.

Two novel double π-extended [n]helicene (n = 5, 6) derivatives (7b and 9) including pentagonal rings have been synthesized and characterized. Both of them have three isomers containing two enantiomers (P6), (M6), and a diastereoisomer in a meso form (P,M). X-ray single crystal analyses suggest that molecules 7b and 9 exhibit offset packing models of (P6,P5)- and (M6,M5)-isomers. Optical resolution of the resultant compound 7b was finished, and their chiroptical properties, as well as the DFT calculations, were also examined.

The effect of metformin on homocysteine levels in patients with polycystic ovary syndrome: A systematic review and meta-analysis.

PURPOSE: Metformin is widely used as an insulin sensitizer in polycystic ovary syndrome (PCOS) patients. However, previous studies have found that the effect of metformin on the level of homocysteine were not consistent in PCOS patients. The aim of this review was to analyze the effect of metformin on homocysteine levels in patients with PCOS patients. METHODS: The Cochrane Library, Pubmed, and Web of Science were searched according to predefined search terms. There is no restriction for publication time and language. RESULTS: Eleven studies were included and the data were extracted. The homocysteine level in PCOS patients was significantly increased after taking metformin (mean difference [MD] -1.33; 95% confidence interval [CI] -2.16 to -0.49, p = 0.002). Subgroup analysis showed that the level of homocysteine was generally increased in PCOS patients with body mass index (BMI) ≥25 after taking metformin alone (MD -1.82; 95% CI -2.56 to -1.07, p < 0.00001). There was no significant change in homocysteine level in PCOS patients with BMI <25 (MD 0.69; 95% CI -0.41 to 1.79, p = 0.22). Subgroup analysis showed that there was no significant difference when taking metformin >3 months or taking metformin ≤3 months (p = 0.84). Taking metformin ≥1700 mg/days significantly increased homocysteine levels in PCOS patients (MD -2.05; 95% CI -2.40 to -1.70, p < 0.00001). When taking metformin <1700 mg/days, there was no significant difference in homocysteine level in PCOS patients (MD 0.15; 95% CI -1.06 to 1.37, p = 0.80). The difference between the two subgroups was significant (p = 0.0006). There was no significant difference in vitamin B12 level before and after metformin treatment (MD 24.70; 95% CI -22.54 to 71.93, p = 0.31). There was a decrease in serum folic acid level after metformin administration (MD 1.03; 95% CI 0.80 to 1.26, p < 0.00001). CONCLUSION: Taking metformin alone increased homocysteine levels and decreased folic acid levels in nonpregnant PCOS patients. And, it was suggested that the dosage of metformin should be less than 1700 mg/days. The supplement of folic acid and B vitamins during metformin administration may be essential in nonpregnant PCOS patients. We should pay much attention to the potential effect of metformin in PCOS patients.

Hydroxylation, Epoxidation, and Dehydrogenation of Capsaicin by a Microbial Promiscuous Cytochrome P450 105D7.

Cytochrome P450 enzymes (P450s) are versatile biocatalysts, which insert a molecular oxygen into inactivated C-H bonds under mild conditions. CYP105D7 from Streptomyces avermitilis has been reported as a bacterial substrate-promiscuous P450 which catalyzes the hydroxylation of 1-deoxypentalenic acid, diclofenac, naringenin, compactin and steroids. In this study, CYP105D7 catalyzes hydroxylation, epoxidation and dehydrogenation of capsaicin, a pharmaceutical agent, revealing its functional diversity. The kinetic parameters of the CYP105D7 oxidation of capsaicin were determined as Km =311.60±87.30 µM and kcat =2.01±0.33 min-1 . In addition, we conducted molecular docking, mutagenesis and substrate binding analysis, indicating that Arg81 plays crucial role in the capsaicin binding and catalysis. To our best knowledge, this study presents the first report to illustrate that capsaicin can be catalyzed by prokaryotic P450s.

Diagnostic and therapeutic ERß, HER2, BRCA biomakers in the histological subtypes of lung adenocarcinoma according to the IASLC/ATS/ERS classification.

Several studies revealed that non-small cell lung cancers (NSCLCs) frequently express ER, PR, HER2 and carry BRCA mutation. However, these markers in histological subtypes of lung adenocarcinoma have not been thoroughly investigated. We retrospectively evaluated a total of 640 lung adenocarcinoma samples for ERα, ERß, PR and HER2 expression by immunohistochemistry and western-blotting, for EGFR and BRCA mutation by real-time PCR and sequencing. Furthermore, HER2 amplification and mutation were explored in samples harboring immunopositivity HER2 using fluorescence in situ hybridization and real-time PCR, respectively. The micropapillary and invasive mucinous predominant adenocarcinoma were frequently detected the higher level of cytoplasmic ERß (64.9% and 56.6%), HER2 (68.1% and 60.1%) protein expression. But, amplification of HER2 was detected in only three cases (3/110, 2.7%) and 26 HER2 mutations in 110 cases were identified (23.6%) in the HER2 immunopositivity patients. Logistic regression analysis showed that cytoplasmic ERß (P = 0.032) and HER2 (P = 0.015) expression were independently associated with EGFR mutation. 8 patients (8/640, 1.25%) harbored pathogenic BRCA mutations, 6 with germline BRCA mutations and 2 with somatic BRCA1 mutations were detected with lacking ERß, PR and HER2 expression. Acinar predominant adenocarcinoma had the higher percentage of BRCA mutations than other subtypes. A systematic examination of ERß, HER2 and BRCA biomarkers could potentially be useful to diagnosis and identify patients with the histological subtypes of lung adenocarcinoma, who might benefit from the further individualized treatment of anti-hormone, anti-HER2 and/or PARP inhibitors therapeutics.

Hyperspectral Imaging as a Potential Online Detection Method of Microplastics.

Microplastic pollution in aquatic environment has raised concern and as a result a number of studies have recently been published to find solutions for its rapid increase. Different methods have been proposed for microplastic identification. Spectral imaging shows a lot of promise for polymer identification; however, the identification time needs to be improved. Hyperspectral imaging (HSI) combined with chemometric analysis can reduce the identification times. In this study, we provide a review of recent studies related to polymer identification using HSI with a focus on the adopted classification algorithm and its factors for the online implementation of HSI. Furthermore, we review the limit of detection by HSI and the effect of particle size on classification accuracy. Additionally, performance of this method for various types of samples is also discussed. We conclude that HSI is possible to be a fast alternative for online microplastic detection.