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"Zhuang, Yan-Yan"
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حلم قرية دينغ : رواية
استنادا إلى فاعليات حقيقية وقعت بداية التسعينيات ؛ إذ أهلك مصيبة الإيدز قرى بأكملها، قرى سعى سكانها، بتحفيز من المسؤولين المحليين، الفرار من الفقر المدقع من خلال بيع الدم. وقائع قد تظهر من \"ديستوبيا\" متخيلة ؛ من فساد المسؤولين وصمت الحكام إلى تهديد الإنس وتسليعهم، ومن خبث التجار وانحطاط الأخلاق إلى جهل القرويين الحالمين بالثراء العاجل. تلك حكاية عن الوفاة والتنصل من المسؤوليات، عن جرائم بدون قصاص، عن جشع يمسخ علاقات الأسرة وأحلام كالنبوءات. بنثر آسر الحسن، ونبرة ولد بريء، نقرأ رواية \"يان ليانكه\"، وهو يؤسطر الزمان الماضي المطموس رسميا.
Book
Acute pancreatitis in intraductal papillary mucinous neoplasm: a single-center retrospective cohort study with systematic review and meta-analysis
Background
Intraductal papillary mucinous neoplasm (IPMN) is a cystic tumor of the pancreas arising from abnormal papillary proliferation of ductal epithelial cells, and is a precancerous lesion of pancreatic malignancy. This study aimed to evaluate associations between acute pancreatitis (AP) and histologic subtypes of IPMN.
Methods
In the clinical study, patients with IPMN confirmed by surgical resection specimens at our institute between 2009 and 2021 were eligible for inclusion. Associations and predictive accuracy of AP on the presence of HGD were determined by logistic regressions. In addition, a systematic review and meta-analysis was conducted through literatures upon search in PubMed, Embase, CENTRAL, China National Knowledge Infrastructure (CKNI), and Wanfang database, up to June, 2023. Pooled effects of the associations between AP and HGD and intestinal epithelial subtype subtype, shown as odds ratios (ORs) with 95% confidence intervals (CIs), were calculated using random effects model.
Results
The retrospective cohort study included 47 patients (32 males, 15 females) diagnosed with IPMN at our center between 2009 and 2021, including 11 cases with AP (median 62 years) and 36 cases (median 64.5 years) without. Accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of AP in predicting HGD were 78.7%, 57.1%, 82.5%, 36.4%, and 91.7%, respectively. Univariate logistic regression analysis showed that AP group had greater odds of presence of HGD (OR: 6.29,95% CI: 1.14–34.57) than non-AP group. Meta-analysis of five case-control studies in the literature included 930 patients and showed that AP-IPMN patients had higher odds for HGD (OR: 2.13, 95% CI 1.38–3.29) and intestinal epithelial subtype (OR: 5.38, 95% CI: 3.50–8.27) compared to non-AP IPMN.
Conclusions
AP is predictive of malignancy in patients with IPMN.
Journal Article
Mitapivat: A Review in Pyruvate Kinase Deficiency in Adults
Mitapivat (Pyrukynd
®
), an oral, allosteric activator of pyruvate kinase (PK), is approved in the USA for the treatment of haemolytic anaemia in adults with PK deficiency and in the EU and UK for the treatment of PK deficiency in adults. Mitapivat acts by restoring activity of the red blood cell (RBC) PK enzyme, which is dysfunctional due to genetic mutations in the
PKLR
gene in patients with PK deficiency. In the double-blind placebo-controlled phase III ACTIVATE trial in adults with PK deficiency who were not regularly RBC transfused, mitapivat was superior to placebo in improving haemoglobin levels. In the single-arm phase III ACTIVATE-T trial in adults with PK deficiency who were regularly RBC transfused, a reduction in RBC transfusion burden was observed with mitapivat. In both trials, mitapivat improved other clinical parameters of haemolysis and patient-reported health-related quality of life. At the approved twice-daily dosage range, mitapivat was generally well tolerated, with adverse events generally being mild to moderate in severity. Results from an ongoing extension study in previously enrolled phase III trial patients will be of interest. Currently available data indicate that mitapivat, the first approved disease-modifying drug for PK deficiency in adults, is a valuable treatment option for this rare disease.
Plain Language Summary
Pyruvate kinase (PK) deficiency is a rare hereditary disease caused by mutations affecting the function of the PK enzyme in red blood cells (RBCs) and is characterized by chronic haemolytic anaemia. Treatment options for adults with PK deficiency have historically been limited to supportive care and are themselves associated with potentially serious complications. Oral mitapivat (Pyrukynd
®
) is the first disease-modifying drug to be approved for use in adults with PK deficiency and acts by restoring activity of the dysfunctional RBC PK enzyme. Based on findings from two phase III clinical trials, twice-daily oral mitapivat provided clinical benefit in adults with PK deficiency, both in patients not requiring, and requiring, regular RBC transfusions. Improvements in disease-specific health-related quality of life were observed in adults with PK deficiency treated with mitapivat. Mitapivat was generally well tolerated, with most adverse events being mild to moderate in severity. In conclusion, current evidence indicates that mitapivat is a valuable treatment option for adults with PK deficiency.
Journal Article
Effect of electroosmosis flow and electrolyte circulation on electrokinetic remediation of Pb-contaminated kaolin
Adding acetic acid to specific kaolin induces reverse electroosmotic flow (EOF). The experimental results indicate that the pH of the kaolin after experimentation ranged from 3.78 to 10.48, which did not reach the point of zero charge (pH
PZC
) identified by previous studies as the critical factor causing the reverse EOF. This reverse EOF was attributed to the differential water-binding capabilities of ions, with hydration numbers of CH
3
COO
−
and Na
+
being 6 and 5, respectively, and the distinct migration mechanisms of various ions, notably the unique chain migration of H
+
. EDTA was utilized to complex Pb into PbEDTA
2−
, thereby altering its ionic charge and facilitating its application in the electrokinetic remediation (EKR) of acetic acid-acidified, Pb-contaminated kaolin. This intervention was crucial as it induced the migration of anionic Pb towards the anode. To mitigate polarization near the electrodes, the electrolytes of the anode and cathode were linked and circulated. The results demonstrated a successful Pb removal rate of up to 97.44% while retaining the kaolin's inherent elements, indicating that electrolyte circulation helps maintain soil fertility during EKR by preserving ionic components essential for plant growth.
Graphical abstract
Journal Article
Cell-Free DNA: Hope and Potential Application in Cancer
Cell-free DNA (cfDNA) is easily accessible in peripheral blood and can be used as biomarkers for cancer diagnostics, prognostics, and therapeutics. The applications of cfDNA in various areas of cancer management are attracting attention. In this review article, we discuss the potential relevance of using cfDNA analysis in clinical oncology, particularly in cancer screening, early diagnosis, therapeutic evaluation, monitoring disease progression; and determining disease prognosis.
Journal Article
Advancing osmotic power generation by covalent organic framework monolayer
Osmotic power, also known as ‘blue energy’, is produced by mixing solutions of different salt concentrations, and represents a vast, sustainable and clean energy source. The efficiency of harvesting osmotic power is primarily determined by the transmembrane performance, which is in turn dependent on ion conductivity and selectivity towards positive or negative ions. Atomically or molecularly thin membranes with a uniform pore environment and high pore density are expected to possess an outstanding ion permeability and selectivity, but remain unexplored. Here we demonstrate that covalent organic framework monolayer membranes that feature a well-ordered pore arrangement can achieve an extremely low membrane resistivity and ultrahigh ion conductivity. When used as osmotic power generators, these membranes produce an unprecedented output power density over 200 W m−2 on mixing the artificial seawater and river water. This work opens up the application of porous monolayer membranes with an atomically precise structure in osmotic power generation.The ultrathin thickness, high pore density and short interpore distance of a COF monolayer endow an extremely low membrane resistance and strong pore–pore coupling, which greatly improves the membrane-based osmotic power generation.
Journal Article
Perfluorohexyloctane Ophthalmic Solution: A Review in Dry Eye Disease
Perfluorohexyloctane ophthalmic solution (Miebo
®
) is a single-entity, water-, steroid- and preservative-free, first-in-class semifluorinated alkane that is approved in the USA for the treatment of the signs and symptoms of dry eye disease (DED). DED is often linked with meibomian gland dysfunction (MGD), which causes an excessive evaporation of tears. Perfluorohexyloctane ophthalmic solution stabilizes the lipid layer of the tear film and inhibits tear evaporation by forming a monolayer at the air-liquid interface. In the phase III GOBI and MOJAVE trials in adults with DED associated with MGD, one drop of perfluorohexyloctane ophthalmic solution instilled in each eye four times daily over 8 weeks resulted in statistically significant and clinically meaningful improvements in the signs and symptoms of DED compared with hypotonic saline (0.6%). The agent was generally well tolerated, with most ocular adverse events being mild or moderate in severity. The efficacy and tolerability of perfluorohexyloctane ophthalmic solution was sustained for up to 52 weeks in an extension study (KALAHARI). As the first and currently the only prescription treatment approved in the USA directly addressing the pathophysiology of excessive tear evaporation, perfluorohexyloctane ophthalmic solution is a valuable emerging option for the management of DED.
Plain Language Summary
Dry eye disease (DED) is a common eye disorder caused by many factors. In most cases, DED is linked with meibomian gland dysfunction (MGD), which causes an excessive evaporation of tears. Perfluorohexyloctane ophthalmic solution (Miebo
®
), a single-entity, water-, steroid- and preservative-free, first-in-class semifluorinated alkane, is approved in the USA for the treatment of the signs and symptoms of DED. The agent stabilizes the lipid layer of the tear film and prevents the evaporation of tears by forming a layer on the surface of the tear film. In two phase III clinical trials in adults with MGD-associated DED, one drop of perfluorohexyloctane ophthalmic solution instilled in each eye four times daily over 8 weeks led to significant improvements in the signs and symptoms of DED when compared with hypotonic saline (0.6%). Perfluorohexyloctane ophthalmic solution was generally well tolerated, with most ocular adverse events being mild or moderate in severity. Thus, as the first and currently the only prescription treatment approved in the USA directly addressing excessive tear evaporation, perfluorohexyloctane ophthalmic solution is a valuable emerging option for the management of DED.
Journal Article
Enhanced antitumor efficacy in colon cancer using EGF functionalized PLGA nanoparticles loaded with 5-Fluorouracil and perfluorocarbon
Background
Tumor recurrence and metastasis occur at a high rate in patients with colon cancer. Identification of effective strategies for the treatment of colon cancer is critical. Recently, poly (lactic-co-glycolic acid) (PLGA) has been shown to have potential as a broad therapeutic drug delivery system. We designed a dual-loaded nanoparticle drug delivery system to overcome the limitations of chemotherapeutic drugs used to treat colon cancer.
Methods
We developed epidermal growth factor (EGF) functionalized PLGA nanoparticles (NPs) co-loaded with 5-fluorouracil (5Fu) and perfluorocarbon (PFC) (EGF-PLGA@5Fu/PFC) for targeted treatment of colon cancer. CCK-8 assay, Hoechst33342 staining and flow cytometry were performed to investigate the functions of EGF-PLGA@5Fu/PFC NPs in SW620 cells. Beside, animal experiment, histological analysis and immunofluorescence staining were adopted to further confirm the role of EGF-PLGA@5Fu/PFC NPs in vivo
.
Results
The findings showed that EGF-PLGA@5Fu /PFC NPs had an average size 200 nm and a 5Fu-loading efficiency of 7.29%. Furthermore, in vitro release was pH-sensitive. Targeted EGF-PLGA@5Fu/PFC NPs exhibited higher cellular uptake than non-targeted NPs into colon cancer cells. In addition, EGF-PLGA@5Fu/PFC NPs suppressed cell viability and induced apoptosis in SW620 cells to a greater extent than non-targeted NPs. In tumor xenografted mice, EGF-PLGA@5Fu/PFC NPs suppressed tumor growth more effectively than 5Fu, PLGA@5Fu or PLGA@5Fu/PFC NPs. Histopathological analysis further demonstrated that EGF-targeted NPs inhibited tumor growth to a greater extent than non-targeted or non-NP treatments. The improved therapeutic outcomes observed in this study were due to relief of tumor hypoxia by transport of oxygen by PFC to the tumors.
Conclusion
We constructed a biocompatible nanodrug delivery system based on functionalized nanoparticles that provided a novel strategy for selective delivery of chemotherapy drugs to tumors.
Journal Article
Dual-gated single-molecule field-effect transistors beyond Moore’s law
As conventional silicon-based transistors are fast approaching the physical limit, it is essential to seek alternative candidates, which should be compatible with or even replace microelectronics in the future. Here, we report a robust solid-state single-molecule field-effect transistor architecture using graphene source/drain electrodes and a metal back-gate electrode. The transistor is constructed by a single dinuclear ruthenium-diarylethene (Ru-DAE) complex, acting as the conducting channel, connecting covalently with nanogapped graphene electrodes, providing field-effect behaviors with a maximum on/off ratio exceeding three orders of magnitude. Use of ultrathin high-
k
metal oxides as the dielectric layers is key in successfully achieving such a high performance. Additionally, Ru-DAE preserves its intrinsic photoisomerisation property, which enables a reversible photoswitching function. Both experimental and theoretical results demonstrate these distinct dual-gated behaviors consistently at the single-molecule level, which helps to develop the different technology for creation of practical ultraminiaturised functional electrical circuits beyond Moore’s law.
Conventional silicon-based transistors, which sit at the heart of every computer, are fast approaching the limit of miniaturisation. Here, Meng et al demonstrate a field-effect transistor composed of a single rutheniumdiarylethene molecule with large on/off ratio.
Journal Article
The association between lipid accumulation products and bone mineral density in U.S. Adults, a nationally representative cross-sectional study
LAP (lipid accumulation products) is a new indicator that estimates lipid overaccumulation and central obesity in our bodies. Nevertheless, the relationship of LAP with bone mineral density (BMD) has not been well established. This study aims to assess the association of LAP with BMD in U.S. adults. Multivariate linear regression was employed to detect the relationship of LAP with lumbar BMD in adult Americans. Subgroup and interaction tests were employed to detect the robustness of our findings. Restricted cubic spline (RCS) and threshold effect analysis were used to assess the nonlinear correlation of LAP with lumbar BMD. A total of 3883 participants consisted of 2117 (54.52%) men and 1766 (45.48%) women. The mean age of participants was 39.33 ± 11.53 years. After adjusting all covariates, we found a negative association of ln-LAP with lumbar BMD (β= -0.011, 95% CI: -0.019, -0.004). Threshold effect analysis identified the inflection points of 2.846. The results showed no correlation to the left of the saturation point but a significant negative correlation to the right. Interaction analyses indicated that all subgroups have no effect on this association (P > 0.05). Our study reported a nonlinear negative association of LAP with lumbar BMD. A large LAP may be associated with reduced BMD in American adults. These findings support the clinical utility of LAP as a predictor of osteoporosis and provide valuable insights into developing early intervention strategies for osteoporosis populations.
Journal Article