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The erosion of surface pipelines induced by proppant flowback during shale gas production is significant. The surface pipelines in a shale gas field in the Sichuan Basin experienced perforation failures after only five months of service. To investigate the erosion features of L360N, coatings, and ceramics and optimize the selection of two protective materials, a gas-solid two-phase flow jet erosion experimental device was used to explore the erosion resistance of L360N, coatings, and ceramics under different impact velocities (15 m/s, 20 m/s, and 30 m/s). An energy dispersive spectroscope, a scanning electron microscope, and a laser confocal microscope were employed to analyze erosion morphologies. With the increase in flow velocity, the erosion depth and erosion rate of L360N, coating, and ceramic increased and peaked under an impact velocity of 30 m/s. The maximum erosion rate and maximum erosion depth of L360N were, respectively, 0.0350 mg/g and 37.5365 µm. Its primary material removal mechanism was the plowing of solid particles, and microcracks were distributed on the material surface under high flow velocities. The maximum erosion rate and maximum erosion depth of the coating were, respectively, 0.0217 mg/g and 18.9964 µm. The detachment of matrix caused by plowing is the main material removal mechanism. The maximum erosion rate and maximum erosion depth of ceramics were, respectively, 0.0108 mg/g and 12.4856 µm. The erosion mechanisms were micro-cutting and plowing. Under different particle impact velocities, different erosion morphologies were observed, but the primary erosion mechanism was the same. The erosion resistance of the ceramics was higher than that of the coatings. Therefore, ceramic lining materials could be used to protect the easily eroded parts, such as pipeline bends and tees, and reduce the failure rate by more than 93%. The study provided the data and theoretical basis for the theoretical study on oil and gas pipeline erosion and pipeline material selection.

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Adding corrosion inhibitors is considered to be a cost-effective way to inhibit metal corrosion. In this study, we report the synthesis of a bi-mannich base corrosion inhibitor (BMT) with an impressive inhibition efficiency on carbon steel in H2S and HCl co-existing solution. At the BMT concentration of 9 ppm, the inhibition efficiency (η) of 96.9%, 97.6% and 98.0% were determined by weight loss, potentiodynamic polarization and electrochemical impedance spectroscopy, respectively. The adsorption of BMT on the carbon steel surface follows the Langmuir adsorption isotherm, and the calculated free energy indicates that the adsorption is a spontaneous process. This research also delves into understanding the adsorption behavior and corrosion inhibition mechanism of BMT on carbon steel surfaces through quantum chemistry calculations. The results of this study provide guidance for the application of BMT as a corrosion inhibitor in sour and acid environments.

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BACKGROUND: To provide reference for clinical development of ADCs in the industry, we analyzed the landscape and characteristics of clinical trials about antibody-drug conjugates (ADCs). METHOD: Clinical trials to study ADCs used for the pharmacotherapy of cancers initiated by the sponsor were searched in the Cite line Pharma Intelligence (Trialtrove database), and the landscape and characteristics of these clinical trials were analyzed from multiple perspectives, such as the number, phases, status, indications, and targets of the clinical trials. RESULT: As of December 31, 2022, a total of 431 clinical trials have been initiated to study ADCs used for the pharmacotherapy of cancers, and the number of the last 10 years was 5.5 times as large as the first 11 years. These clinical trials involved 47 indications, including breast cancer, lymphoma (lymphoma, non-Hodgkin's and lymphoma, Hodgkin's), unspecified solid tumor, bladder cancer and lung cancer (lung, non-small cell cancer and lung, small cell cancer). As for each of these five indications, 50 + clinical trials have been carried out, accounting for as high as 48.50% (454/936). ADCs involve 38 targets, which are relatively concentrated. Among them, ERBB2 (HER2) and TNFRSF8 (CD30) involve in 100 + registered clinical trials, and TNFRSF17 (BCMA), NECTIN4 and CD19 in 10 + trials. The clinical trials for these five targets account for 79.02% (354/448) of the total number. Up to 93.97% (405/431) of these clinical trials explored the correlation between biomarkers and efficacy. Up to 45.91% (292/636) of Lots (lines of treatment) applied in the clinical trials were the second line. Until December 31, 2022, 54.52% (235/431) of the clinical trials have been completed or terminated. CONCLUSION: ADCs are a hotspot of research and development in oncology clinical trials, but the indications, targets, phases, and Lot that have been registered are seemingly relatively concentrated at present. This study provides a comprehensive analysis which can assist researchers/developer quickly grasp relevant knowledge to assess a product and also providing new clues and ideas for future research.

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Introduction: Cadonilimab (AK104) is an innovative human programmed cell death-1 (PD-1)/cytotoxic T lymphocyte antigen-4 (CTLA-4) bispecific antibody. Compared with the combination therapy of PD-1 and CTLA-4 blockers, less cellular toxicity of cadonilimab was significantly manifested. As one of the characteristic adverse effects of cadonilimab, infusion-related reactions (IRRs) represent fever, chills, rash, decreased blood pressure, and other symptoms. Case Presentation: Here, we documented seven cases of IRRs after the administration of cadonilimab. The symptoms of IRRs were relieved after the discontinuation of cadonilimab and the administration of diphenhydramine, dexamethasone, and cimetidine. Notably, 3 patients were able to tolerate the subsequent cadonilimab therapy under the pretreatment. Conclusion: In this study, we discovered that cadonilimab-related IRRs might be lessened or prevented by administering medication and the proper pretreatment and lowering the infusion rate.

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Angiogenesis is hijacked by cancer to support tumor growth. RNA modifications such as N6-methyladenosine (m6A) can regulate several aspects of cancer, including angiogenesis. Here, we find that m6A triggers angiogenesis in lung cancer by upregulating VEGFA, a central regulator of neovasculature and blood vessel growth. m6A-sequencing and functional studies confirmed that m6A modification of the 5'UTR (untranslated region) of VEGFA positively regulates its translation. Specifically, methylation of a 5'UTR internal ribosome entry site (IRES) recruited the YTHDC2/eIF4GI complex to trigger cap-independent translation initiation. Intriguingly, the m6A methylation site A856 of the 5'UTR was located within the conserved upstream open reading frame (uORF) of VEGFA IRES-A, which overcomes uORF-mediated translation suppression while facilitating G-quadruplex-induced translation of VEGFA. Targeted specific demethylation of VEGFA m6A significantly decreased expression of VEGFA and reduced lung cancer cell-driven angiogenesis. In vivo and clinical data confirmed the positive effects of m6A modification of VEGFA on angiogenesis and tumor growth of lung cancer. This study not only reveals that the m6A/VEGFA axis is a potential target for lung cancer therapy but also expands our understanding of the impact of m6A modification of IRES in the 5'UTR of mRNA on translation regulation. SIGNIFICANCE: Methylation of the 5'UTR IRES of VEGFA mRNA increases cap-independent translation via recruitment of the YTHDC2/eIF4GI complex, which stimulates angiogenesis to promote lung tumor growth.

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Surgery plays an irreplaceable role in the prevention, diagnosis, staging, reconstruction, and rehabilitation in the overall management of cancer. Nevertheless, it is difficult for surgeons and nurses to take into account the details of medication management, considering the impact of  surgery on the patient's physical function and the complexity of anti-tumor  treatment with comorbidity. The pharmaceutical care services previously  provided by pharmacists in oncology focus more on the internal medicine  system, not widely the surgical field. At present, the pharmaceutical working  mode in oncology surgery has not well been formed around China, and the  whole process medication management needs to be improved. In 2015, the  GuangDong Pharmaceutical Association came up with the concept of  surgical pharmacist in China and subsequently created its position. In 2021, the GuangDong Pharmaceutical Association established a new discipline  termed "surgical pharmacy", which is the knowledge system of surgical pharmacists, and also tried to differentiate surgical pharmacy into  diverse areas, such as oncology surgical pharmacy. This article introduced a  working mode of surgical pharmacists in China that providing pharmaceutical  care services in perioperative period around anti-tumor, anti- infection, anesthesia, anticoagulation, blood pressure, blood glucose, nutrition, and pain management, to improve quality of life for patients.

La cirugía desempeña un papel insustituible en la prevención, diagnóstico, estadificación, reconstrucción y rehabilitación en el tratamiento  global del cáncer. Sin embargo, es difícil que cirujanos y personal de  enfermería tengan en cuenta todos los aspectos de la gestión de la medicación,  como el impacto de la cirugía en la función física del paciente y la  complejidad del tratamiento antitumoral con sus comorbilidades. Los servicios  de atención farmacéutica que anteriormente prestaban los farmacéuticos en  oncología se centraban más en aspectos de la medicina interna, y no  ampliamente en el ámbito quirúrgico. En la actualidad, el modo de trabajo  farmacéutico en la cirugía oncológica aún no está definido en China, y existe  una necesidad de mejorar la gestión de la medicación de todo el proceso  asistencial. En 2015, la Asociación Farmacéutica de GuangDong propuso la  creación del rol de farmacéutico quirúrgico en China y posteriormente creó su  puesto de trabajo. En 2021, la Asociación Farmacéutica de GuangDong  Estableció una nueva disciplina denominada "farmacia quirúrgica", que es el  área de conocimiento de los farmacéuticos quirúrgicos, y también intentó  diferenciar la farmacia quirúrgica en distintas subáreas, como la farmacia  quirúrgica oncológica. Este artículo presenta el modo de trabajo de los  farmacéuticos quirúrgicos en China, que proporciona servicios de atención  farmacéutica en el periodo perioperatorio de los pacientes incorporando los  distintos aspectos del tratamiento antitumoral, control de infecciones,  anestesia, anticoagulación, control de la presión arterial y la glucosa en  sangre, nutrición y tratamiento del dolor, con el objetivo de mejorar la calidad  de vida de los pacientes.

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A key factor for productive DNA-encoded libraries is the chemical diversity of the small molecule moiety attached to an encoding DNA oligomer. The library structure diversity is often limited to DNA-compatible chemical reactions in aqueous media. Herein, we describe a facile process for reducing aryl nitro groups to aryl amines by using sodium dithionite (Na2S2O4). The new protocol offers simple operation and circumvents the pyrophoric potential of the conventional method (Raney nickel). The utility of this method is demonstrated by the versatile synthesis of benzimidazoles on DNA.

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La cirugía desempeña un papel insustituible en la prevención, diagnóstico, estadificación, reconstrucción y rehabilitación en el tratamiento globaldel cáncer. Sin embargo, es difícil que cirujanos y personal de enfermeríatengan en cuenta todos los aspectos de la gestión de la medicación, comoel impacto de la cirugía en la función física del paciente y la complejidaddel tratamiento antitumoral con sus comorbilidades. Los servicios de atenciónfarmacéutica que anteriormente prestaban los farmacéuticos en oncología secentraban más en aspectos de la medicina interna, y no ampliamente en elámbito quirúrgico. En la actualidad, el modo de trabajo farmacéutico en lacirugía oncológica aún no está definido en China, y existe una necesidad demejorar la gestión de la medicación de todo el proceso asistencial. En 2015,la Asociación Farmacéutica de GuangDong propuso la creación del rol defarmacéutico quirúrgico en China y posteriormente creó su puesto de trabajo.En 2021, la Asociación Farmacéutica de GuangDong estableció una nuevadisciplina denominada “farmacia quirúrgica”, que es el área de conocimientode los farmacéuticos quirúrgicos, y también intentó diferenciar la farmaciaquirúrgica en distintas subáreas, como la farmacia quirúrgica oncológica.Este artículo presenta el modo de trabajo de los farmacéuticos quirúrgicosen China, que proporciona servicios de atención farmacéutica en el periodoperioperatorio de los pacientes incorporando los distintos aspectos del tratamiento antitumoral, control de infecciones, anestesia, anticoagulación, controlde la presión arterial y la glucosa en sangre, nutrición y tratamiento del dolor,con el objetivo de mejorar la calidad de vida de los pacientes. (AU)

Surgery plays an irreplaceable role in the prevention, diagnosis, staging, reconstruction, and rehabilitation in the overall management of cancer. Nevertheless, it is difficult for surgeons and nurses to take into accountthe details of medication management, considering the impact of surgeryon the patient’s physical function and the complexity of anti-tumor treatmentwith comorbidity. The pharmaceutical care services previously provided bypharmacists in oncology focus more on the internal medicine system, notwidely the surgical field. At present, the pharmaceutical working mode inoncology surgery has not well been formed around China, and the wholeprocess medication management needs to be improved. In 2015, theGuangDong Pharmaceutical Association came up with the concept of surgical pharmacist in China and subsequently created its position. In 2021,the GuangDong Pharmaceutical Association established a new disciplinetermed “surgical pharmacy”, which is the knowledge system of surgicalpharmacists, and also tried to differentiate surgical pharmacy into diverseareas, such as oncology surgical pharmacy. This article introduced a working mode of surgical pharmacists in China that providing pharmaceutical care services in perioperative period around anti-tumor, anti-infection,anesthesia, anticoagulation, blood pressure, blood glucose, nutrition, andpain management, to improve quality of life for patients. (AU)

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AIMS: A lot of medication risks related to high-dose methotrexate (HDMTX) therapy still remain to be identified and standardized. This study aims to establish an evidence-based practice guideline for individualized medication of HDMTX. METHODS: The practice guideline was launched by the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society. The guideline was developed following the WHO handbook for guideline development and the methodology of evidence-based medicine (EBM). The guideline was initially registered in the International Practice Guidelines Registry Platform (IPGRP-2017CN021). Systematic reviews were conducted to synthesize available evidence. A multicentre cross-sectional study was conducted using questionnaires to evaluate patients' perception and willingness concerning individualized medication of HDMTX. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the quality of evidence and to grade the strength of recommendations. RESULTS: Multidisciplinary working groups were included in this guideline, including clinicians, pharmacists, methodologists, pharmacologists and pharmacoeconomic specialists. A total of 124 patients were involved to integrate patient values and preferences. Finally, the guideline presents 28 recommendations, regarding evaluation prior to administration (renal function, liver function, pleural effusion, comedications, genetic testing), pre-treatment and routine dosing regimen, therapeutic drug monitoring (necessity, method, timing, target concentration), leucovorin rescue (initial timing, dosage regimen and optimization), and management of toxicities. Of these, 12 are strong recommendations. CONCLUSIONS: We developed an evidence-based practice guideline with respect to HDMTX medication using a rigorous and multidisciplinary approach. This guideline provides comprehensive and practical recommendations involving the whole process of HDMTX administration to health care providers.

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Previous exposure-response analyses for rituximab suggest that higher rituximab concentrations were associated with an improvement in efficacy, however, clinical studies investigating a higher rituximab dose had mixed results. To further explore the exposure-response relationship of rituximab, a prospective observational analysis was performed involving 121 newly diagnosed patients with diffuse large B-cell lymphoma treated with triweekly rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). The trough concentration in the first cycle (C1-trough ) was significantly higher in patients achieving complete response (CR) compared with patients that did not achieve CR (22.00 µg/ml vs. 16.62 µg/ml, p = 0.0016), however, this difference between the two groups disappeared in later cycles. The relationship between rituximab C1-trough and achieving a CR was confirmed by matched-pair logistic regression analysis (odds ratio, 0.79; p = 0.0020). In addition, a higher C1-trough (≥18.40 µg/ml) was associated with longer progression-free survival (p < 0.0001) and overall survival (p = 0.0038). The percentages of patients that did not achieve a CR and had recurrence after CR within 24 months were 35% and 22.50%, respectively, for patients with a C1-trough less than or equal to 18.40 µg/ml, compared with 12.35% and 6.17% for patients with C1-trough greater than 18.40 µg/ml. Disease stage was found to be the most significant influencing factor of C1-trough , with 51.02% of patients at stage IV with an observed C1-trough less than 18.40 µg/ml. For these advanced patients, population pharmacokinetic simulations using an established model suggest that a loading dose of 800 mg/m2  may help to improve clinical outcomes.

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Ceritinib and alectinib are recommended as the second-line therapies in the 2019 Chinese Society of Clinical Oncology (CSCO) guidelines for patients with anaplastic lymphoma kinase (ALK) positive non-small-cell lung cancer (NSCLC) in whom the first-line therapy has failed, but no optimal second-line treatment has been identified. Before 2018, the approved dose of ceritinib in the United States and many other countries was 750 mg/d fasted. In China, the approved dose was 450 mg/d fed although the dose of 750 mg/d fasted is still used in clinical practices. In our current case, a clinical pharmacist was involved in the selection and dose adjustment of a targeted drug for an ALK-positive NSCLC patient. The selection of second-line targeted drugs is based mainly on the results of clinical trials and real-world data of ceritinib and aletinib, along with the comprehensive analysis of health insurance policy, pharmacoeconomics, and drug accessibility. Alectinib may be more efficacious than ceritinib is in second-line settings. However, in our current case, the patient finally chose ceritinib after considering the drug prices and the health insurance policy. The clinical pharmacist optimized the dosage of ceritinib from 750 mg/d fasted to 450 mg/d fed, which not only improved the patient's medication compliance but also ensured the safety and efficacy of the drug; in addition, it lowered the financial burden of both the health insurance system and the patient, offering a good example for rational drug use and health insurance cost reduction. In conclusion, in choosing second-line targeted therapy for ALK-rearranged NSCLC, a variety of factors should be considered, including clinical efficacy, adverse effects, health insurance policy, drug price, and drug accessibility, and the dosage of ceritinib should be optimized to 450 mg/d fed in real-world settings.

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This study proposes an encryption scheme combining cellular automata (CA) and DNA encoding to improve security of a coherent optical orthogonal frequency division multiplexing (CO-OFDM) system, wherein key sequences are generated with good randomness and unpredictability by a 4-dimensional hyper-chaotic system. A base scrambling pseudo random binary sequence (PRBS) generated by the CA is introduced, which results in better scrambling effect and randomness in the conventional complex DNA encoding. The randomness, complexity and security of the system is enhanced due to 6 variable keys (key space of ∼10138). An experiment conducted in a 40 GHz 16QAM CO-OFDM system over an 80 km standard single mode fiber (SSMF) shows that the authorized user can successfully decrypt the received signal, while the eavesdroppers cannot derive useful information with bit error rate (BER) at approximately 0.5. An allowable optical signal to noise ratio (OSNR) penalty of 0.5 dB will be introduced to achieve same BER before and after encryption due to the error propagation of cellular automata.

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BACKGROUND: The COVID-19 outbreak has increased challenges associated with health management, especially cancer management. In an effort to provide continuous pharmaceutical care to cancer patients, Sun Yat-sen University Cancer Center (SYSUCC) implemented a remote pharmacy service platform based on its already existing web-based hospital app known as Cloud SYSUCC. OBJECTIVE: The aim of this study was to investigate the characteristics, acceptance, and initial impact of the Cloud SYSUCC app during a COVID-19 outbreak in a tertiary cancer hospital in China. METHODS: The total number of online prescriptions and detailed information on the service were obtained during the first 6 months after the remote service platform was successfully set up. The patients' gender, age, residence, primary diagnosis, drug classification, weekly number of prescriptions, and prescribed drugs were analyzed. In addition, a follow-up telephonic survey was conducted to evaluate patients' satisfaction in using the remote prescription service. RESULTS: A total of 1718 prescriptions, including 2022 drugs for 1212 patients, were delivered to 24 provinces and municipalities directly under the Central Government of China between February 12, 2020, and August 11, 2020. The majority of patients were female (841/1212, 69.39%), and 90.18% (1093/1212) of them were aged 31-70 years old. The top 3 primary diagnoses for which remote medical prescriptions were made included breast cancer (599/1212, 49.42%), liver cancer (249/1212, 20.54%), and thyroid cancer (125/1212, 10.31%). Of the 1718 prescriptions delivered, 1435 (83.5%) were sent to Guangdong Province and 283 (16.5%) were sent to other provinces in China. Of the 2022 drugs delivered, 1012 (50.05%) were hormonal drugs. The general trend in the use of the remote prescription service declined since the 10th week. A follow-up telephonic survey found that 88% (88/100) of the patients were very satisfied, and 12% (12/100) of the patients were somewhat satisfied with the remote pharmacy service platform. CONCLUSIONS: The remote pharmacy platform Cloud SYSUCC is efficient and convenient for providing continuous pharmaceutical care to patients with cancer during the COVID-19 crisis. The widespread use of this platform can help to reduce person-to-person transmission as well as infection risk for these patients. Further efforts are needed to improve the quality and acceptance of the Cloud SYSUCC platform, as well as to regulate and standardize the management of this novel service.

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For follicular lymphoma (FL) with grade 1/2, the complete response (CR) rate of the first-line R-CHOP treatment was significantly low. In this study, we assessed the rationality of the administration of rituximab for FL patients with grade 1/2 based on concentration-response relationship analyses. Thus, we conducted a prospective pharmacokinetic (PK) study in 68 FL patients with grades 1-3 treated with R-CHOP at 21-day intervals. Plasma rituximab concentrations were quantified using ELISA and the population PK modeling was established with Phoenix® NLMETM. The first cycle trough concentration (C1-trough) of rituximab was a significant independent risk factor for achieving CR in matched-pair logistic regression analysis, rather than the concentrations in later cycles; the recommendatory minimum optimal C1-trough was 13.60 µg/mL. Patients with grade 1/2 had significantly lower C1-trough compared with grade 3 (12.21 µg/mL vs. 23.45 µg/mL, P < 0.001), only 30% patients with grade 1/2 could reach 13.60 µg/mL, compared with 91.67% in patients with grade 3, which was in accord with its unsatisfactory CR rates (43.33% vs. 76.32%). The stage indicating the tumor burden (the target) was a crucial influence factor for C1-trough, accounting for 40.70% of its variability, 70% patients with grade 1/2 were stage IV in this study, since the systemic therapy only started at the disseminated disease stage. The initial dose of 1800 mg was recommended by Monte Carlo simulation for patients with grade 1/2. In summary, low C1-trough accounted for low-grade FL's unsatisfactory CR rate, designing the first dosage of rituximab should be a very important component of individualized therapy for FL.

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BACKGROUND: Compared with the standard of care with sunitinib, avelumab plus axitinib can increase progression-free survival in the first-line of advanced renal cell carcinoma (RCC), but the economic effect of the treatment is unknown. The purpose of the research was to evaluate the cost-effectiveness of the avelumab plus axitinib versus sunitinib in first-line treatment for advanced RCC from the US payer perspective. METHODS: A Markov model was developed to evaluate the economic and health outcomes of avelumab plus axitinib vs sunitinib in the first-line setting for advanced RCC. The clinical data were obtained from the JAVELIN Renal 101 Clinical Trials. Deterministic and probabilistic sensitivity analyses were performed to assess uncertainty in the model. Health outcomes were measured in quality-adjusted life-years (QALYs). RESULTS: The incremental cost-effectiveness ratio (ICER) of avelumab plus axitinib compared with sunitinib was $565,232 per QALY, the costs were $884,626 and $669,838, QALYs were 3.67 and 3.29, respectively. Sensitivity analysis demonstrated that differences in utilities in PFS and after progression were the most influential factors within the model. When avelumab was at 30% of the full price or axitinib was at 40% of the full price, avelumab and axitinib were approved to be cost-effective if the WTP threshold was $150,000 per QALY. The subgroup analysis showed the ICER of avelumab plus axitinib compared with sunitinib for the patients with PD-L1-positive tumors was $588,105. CONCLUSION: Avelumab plus axitinib in the first-line treatment was not cost-effective in comparison with sunitinib when the threshold of willingness to pay (WTP) was $150,000 per QALY.

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Bacterial resistance to ß-lactam antibiotics is largely mediated by ß-lactamases, which catalyze the hydrolysis of these drugs and continue to emerge in response to antibiotic use. ß-Lactamases that hydrolyze the last resort carbapenem class of ß-lactam antibiotics (carbapenemases) are a growing global health threat. Inhibitors have been developed to prevent ß-lactamase-mediated hydrolysis and restore the efficacy of these antibiotics. However, there are few inhibitors available for problematic carbapenemases such as oxacillinase-48 (OXA-48). A DNA-encoded chemical library approach was used to rapidly screen for compounds that bind and potentially inhibit OXA-48. Using this approach, a hit compound, CDD-97, was identified with submicromolar potency (Ki = 0.53 ± 0.08 µM) against OXA-48. X-ray crystallography showed that CDD-97 binds noncovalently in the active site of OXA-48. Synthesis and testing of derivatives of CDD-97 revealed structure-activity relationships and informed the design of a compound with a 2-fold increase in potency. CDD-97, however, synergizes poorly with ß-lactam antibiotics to inhibit the growth of bacteria expressing OXA-48 due to poor accumulation into E. coli. Despite the low in vivo activity, CDD-97 provides new insights into OXA-48 inhibition and demonstrates the potential of using DNA-encoded chemistry technology to rapidly identify ß-lactamase binders and to study ß-lactamase inhibition, leading to clinically useful inhibitors.

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Heat stress is a broiler welfare issue and economic deficit to the broiler industry. Water atomizing with three-dimensional forced ventilation, a holding treatment after summer transport for broiler, has been proved to significantly improve water holding capacity of fresh meat. However, effectiveness of this treatment on water retention after freeze-thaw needs to be conducted. Therefore, the objective of this study was to assess whether water atomizing with forced ventilation could increase freeze-thaw meat quality after birds slaughtering. Arbor Acres broiler (n = 105), undergoing 32°C ambient temperature transport, was randomly categorized into 3 treatments: 1) T group, which underwent 45-min transport without rest; 2) TR group, which underwent 45-min transport with 1-h rest; and the 3) TWFR group, which underwent 45-min transport followed by 15-min water atomizing with three-dimensional forced ventilation and 45-min rest. All birds were hot-deboned within 30-min postmortem. A total of 105 breast fillets were collected and split into halves, which left part fillets were kept in 4°C and for meat analysis, the other part fillets, marked with T-F, TR-F, and TWFR-F, were frozen (-18°C) for 1 mo and then thawed overnight for meat quality analysis. Regardless of fresh or frozen treatment among 3 groups, TWFR has the highest pH which was more than 6.01 (P < 0.05). The L* value, drip loss, and cooking loss of TWFR were significantly lower compared to T and TR groups in both fresh and frozen breast fillets (P < 0.05). Compared with the T group, the TWFR meat shows closely microscopic structure which means less water loss channel. The impedance amplitude of the fresh meat was significantly higher than that of the frozen-thawing meat (P < 0.05). TWFR-treated meat has significantly higher impedance module than T and TR meat at 50 Hz frequency region, for both fresh or thawed meat. Among 6 treatments, TWFR fresh meat has significantly highest Q (modulus change ratio) value (P < 0.05). These results indicate that TWFR treatment for 15 min after transport can improve meat quality, which may be due to the improved welfare of broilers transported in hot summer months.

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BACKGROUND: Brain metastasis (BM) is one of the principal causes of mortality for lung cancer patients. While the molecular events that govern BM of lung cancer remain frustrating cloudy. METHODS: The miRNA expression profiles are checked in the paired human BM and primary lung cancer tissues. The effect of miR-143-3p on BM of lung cancer cells and its related mechanisms are investigated. RESULTS: miR-143-3p is upregulated in the paired BM tissues as compared with that in primary cancer tissues. It can increase the invasion capability of in vitro blood brain barrier (BBB) model and angiogenesis of lung cancer by targeting the three binding sites of 3'UTR of vasohibin-1 (VASH1) to inhibit its expression. Mechanistically, VASH1 can increase the ubiquitylation of VEGFA to trigger the proteasome mediated degradation, further, it can endow the tubulin depolymerization through detyrosination to increase the cell motility. m6A methyltransferase Mettl3 can increase the splicing of precursor miR-143-3p to facilitate its biogenesis. Moreover, miR-143-3p/VASH1 axis acts as adverse prognosis factors for in vivo progression and overall survival (OS) rate of lung cancer. CONCLUSIONS: Our work implicates a causal role of the miR-143-3p/VASH1 axis in BM of lung cancers and suggests their critical roles in lung cancer pathogenesis.

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