Role of Selective Histone Deacetylase 6 Inhibitor ACY-1215 in Cancer and Other Human Diseases

The deacetylation process regulated by histone deacetylases (HDACs) plays an important role in human health and diseases. HDAC6 belongs to the Class IIb of HDACs family, which mainly modifies non-histone proteins located in the cytoplasm. HDAC6 plays a key role in tumors, neurological diseases, and inflammatory diseases. Therefore, targeting HDAC6 has become a promising treatment strategy in recent years. ACY-1215 is the first orally available highly selective HDAC6 inhibitor, and its efficacy and therapeutic effects are being continuously verified. This review summarizes the research progress of ACY-1215 in cancer and other human diseases, as well as the underlying mechanism, in order to guide the future clinical trials of ACY-1215 and more in-depth mechanism researches

Key problems in in-situ pyrolysis of tar-rich coal drilling for extraction of coal-based oil and gas resources

Tar-rich coal is a special coal resource with the property of oil and gas resources. Developing the oil and gas resources contained in the tar-rich coal is of great significance for ensuring energy security and realizing the goal of "dual carbon". In-situ pyrolysis of tar-rich coal is a new coal resource development technology. Through some artificial cracks in coal seams, multiple wells can be connected. The coal seam is then heated using some technologies such as electric heating or fluid heating to generate oil and gas resources from the pyrolysis of tar-rich coal. At present, some problems such as coal seam heating mode, optimal pyrolysis temperature, reservoir reconstruction technology and efficient extraction of pyrolysis oil and gas need to be urgently solved. ① There are some defects in the application of reaction heating, conduction heating, and radiation heating in the underground in-situ heating of tar-rich coal. Convection heating based on injection fluid heating is more suitable for the in-situ heating of tar-rich coal. According to different geological conditions, it is still necessary to carry out targeted research work for optimizing the economical and safe heat carrying fluid and creating an efficient pyrolysis atmosphere. The combination of various heating methods is expected to be the breakthrough direction of the underground in-situ heating method of tar-rich coal. ② At present, 350−450 ℃ is generally recognized as the efficient pyrolysis temperature. With different coal characteristics and different pyrolysis atmospheres, the corresponding dominant pyrolysis temperature range is slightly different. The methods of chemical thermodynamics and kinetics for the pyrolysis of tar-rich coal are effective means to predict pyrolysis temperature scientifically. ③ Hydraulic fracturing, supercritical CO2 fracturing, and liquid nitrogen fracturing have some limitations for the in-situ pyrolysis of tar-rich coal. For different geological conditions, it is necessary to select the appropriate reservoir reconstruction scheme through specific objective evaluation. Controllable shock wave technology has the advantage of high efficiency and control in rock fracturing and is expected to be widely used in the in-situ pyrolysis process in the future. ④ The combustible gases produced by the pyrolysis of tar-rich coal are mainly CH4, H2, and CO, accompanied by a high content of CO2, which is easy to be directly extracted. The oil produced by pyrolysis is coal tar with high density and high viscosity, which will condense in large quantities below 180 ℃. There is a risk of wellbore clogging and the key to improving the extraction efficiency of pyrolysis products is to formulate the temperature and pressure maintenance scheme of the extraction well. In addition, the systematic issues such as integrated geological engineering evaluation, in-situ pyrolysis reaction process monitoring, and the whole-process numerical simulation of tar-rich coal should also be focused on in the future research work

Clinical value analysis of simple resection of pancreatic solid pseudopapillary tumor

Objective To explore the clinical application value of simple resection in the treatment of pancreatic solid pseudopapillary tumor(SPT). Methods Retrospective analysis of clinical and follow-up data of pancreatic SPT patients who underwent simple pancreatectomy and conventional pancreatectomy from January 2015 to December 2022 in the pancreatic cystic tumor database of Huashan Hospital, Fudan University. A total of 87 patients with pancreatic SPT, including 14 cases underwent simple resection and 73 cases underwent conventional resection, were included. The average age was (36.2±11.7) years old, and females accounting for 87.4%. Results The accuracy of preoperative imaging diagnosis reached 88.5%. Simple resection had a significant advantage over conventional resection in terms of surgical time [(138.3±56.4) min vs. (241.2±89.2) min, P<0.05]. Simple resection was not inferior to conventional resection in terms of common postoperative complications. Out of 87 cases, only 3 patients in conventional resection group experienced postoperative recurrence and metastasis, and all recurrent patients were still alive. There was no statistically significant difference in postoperative pancreatic endocrine and exocrine dysfunction, and quality of life between simple resection group and conventional resection group. Conclusions Simple resection of pancreatic SPT is reasonable and feasible, but the risks in actual clinical work cannot be ignored. Therefore, selective simple resection of SPT has certain clinical application value

Standby extracorporeal membrane oxygenation: a better strategy for high-risk percutaneous coronary intervention

BackgroundThe incidence of cardiac arrest (CA) during percutaneous coronary intervention (PCI) is relatively rare. However, when it does occur, the mortality rate is extremely high. Extracorporeal cardiopulmonary resuscitation (ECPR) has shown promising survival rates for in-hospital cardiac arrests (IHCA), with low-flow time being an independent prognostic factor for CA. However, there is no definitive answer on how to reduce low-flow time.MethodsThis retrospective study, conducted at a single center, included 39 patients who underwent ECPR during PCI between January 2016 and December 2022. The patients were divided into two cohorts based on whether standby extracorporeal membrane oxygenation (ECMO) was utilized during PCI: standby ECPR (SBE) (n = 13) and extemporaneous ECPR (EE) (n = 26). We compared the 30-day mortality rates between these two cohorts and investigated factors associated with survival.ResultsCompared to the EE cohort, the SBE cohort showed significantly lower low-flow time (P < 0.01), ECMO operation time (P < 0.01), and a lower incidence of acute kidney injury (AKI) (P = 0.017), as well as peak lactate (P < 0.01). Stand-by ECMO was associated with improved 30-day survival (p = 0.036), while prolonged low-flow time (p = 0.004) and a higher SYNTAX II score (p = 0.062) predicted death at 30 days.ConclusionsStandby ECMO can provide significant benefits for patients who undergo ECPR for CA during PCI. It is a viable option for high-risk PCI cases and may enhance the overall prognosis. The low-flow time remains a critical determinant of survival

Disentangling the effects of vapor pressure deficit on northern terrestrial vegetation productivity

The impact of atmospheric vapor pressure deficit (VPD) on plant photosynthesis has long been acknowledged, but large interactions with air temperature (T) and soil moisture (SM) still hinder a complete understanding of the influence of VPD on vegetation production across various climate zones. Here, we found a diverging response of productivity to VPD in the Northern Hemisphere by excluding interactive effects of VPD with T and SM. The interactions between VPD and T/SM not only offset the potential positive impact of warming on vegetation productivity but also amplifies the negative effect of soil drying. Notably, for high-latitude ecosystems, there occurs a pronounced shift in vegetation productivity\u27s response to VPD during the growing season when VPD surpasses a threshold of 3.5 to 4.0 hectopascals. These results yield previously unknown insights into the role of VPD in terrestrial ecosystems and enhance our comprehension of the terrestrial carbon cycle\u27s response to global warming

Proteomic analysis of differential proteins in pancreatic carcinomas: Effects of MBD1 knock-down by stable RNA interference

<p>Abstract</p> <p>Background</p> <p>Methyl-CpG binding domain protein 1 (MBD1), a suppressor of gene transcription, may be involved in inactivation of tumor suppressor genes during tumorigenesis. Over-expression of MBD1 has been reported in human pancreatic carcinomas.</p> <p>Methods</p> <p>In this study, we established a MBD1-knock-down pancreatic cancer cell line (BxPC-3) using stable RNA interference, to compare the proteomic changes between control and MBD1-knock-down cells using two-dimensional gel electrophoresis and mass spectrometry.</p> <p>Results</p> <p>We identified five proteins that were up-regulated and nine proteins that were down-regulated. Most of the identified proteins are involved in tumorigenesis, some are prognostic biomarkers for human malignant tumors.</p> <p>Conclusion</p> <p>Our data suggest that these differential proteins may be associated with the function of MBD1, and provide some insight into the functional mechanism of MBD1 in the development of pancreatic cancer.</p

Association of inpatient use of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers with mortality among patients with hypertension hospitalized with COVID-19

Rationale: Use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension. Objective: To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in COVID-19 patients with hypertension. Methods and Results: This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [IQR 55-68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [IQR 57-69]; 53.5% men), who were admitted to nine hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020. Unadjusted mortality rate was lower in the ACEI/ARB group versus the non-ACEI/ARB group (3.7% vs. 9.8%; P = 0.01). In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted HR, 0.42; 95% CI, 0.19-0.92; P =0.03). In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted HR, 0.37; 95% CI, 0.15-0.89; P = 0.03). Further subgroup propensity score-matched analysis indicated that, compared to use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted HR, 0.30; 95%CI, 0.12-0.70; P = 0.01) in COVID-19 patients with hypertension. Conclusions: Among hospitalized COVID-19 patients with hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB non-users. While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk