ABCB1 attenuates brain exposure to the KRASG12C inhibitor opnurasib whereas binding to mouse carboxylesterase 1c influences its plasma exposure.

Opnurasib (JDQ443) is a newly developed oral KRASG12C inhibitor, with a binding mechanism distinct from the registered KRASG12C inhibitors sotorasib and adagrasib. Phase I and II clinical trials for opnurasib in NSCLC are ongoing. We evaluated the pharmacokinetic roles of the ABCB1 (P-gp/MDR1) and ABCG2 (BCRP) efflux and OATP1 influx transporters, and of the metabolizing enzymes CYP3A and CES1 in plasma and tissue disposition of oral opnurasib, using genetically modified cell lines and mouse models. In vitro, opnurasib was potently transported by human (h)ABCB1 and slightly by mouse (m)Abcg2. In Abcb1a/b- and Abcb1a/b;Abcg2-deficient mice, a significant ∼100-fold increase in brain-to-plasma ratios was observed. Brain penetration was unchanged in Abcg2-/- mice. ABCB1 activity in the blood-brain barrier may therefore potentially limit the efficacy of opnurasib against brain metastases. The Abcb1a/b transporter activity could be almost completely reversed by co-administration of elacridar, a dual ABCB1/ABCG2 inhibitor, increasing the brain penetration without any behavioral or postural signs of acute CNS-related toxicity. No significant pharmacokinetic roles of the OATP1 transporters were observed. Transgenic human CYP3A4 did not substantially affect the plasma exposure of opnurasib, indicating that opnurasib is likely not a sensitive CYP3A4 substrate. Interestingly, Ces1-/- mice showed a 4-fold lower opnurasib plasma exposure compared to wild-type mice, whereas no strong effect was seen on the tissue distribution. Plasma Ces1c therefore likely binds opnurasib, increasing its retention in plasma. The obtained pharmacokinetic insights may be useful for further optimization of the clinical efficacy and safety of opnurasib, and might reveal potential drug-drug interaction risks.

Impact of loperamide on the pharmacokinetics and tissue disposition of ritonavir-boosted oral docetaxel therapy; a preclinical assessment.

PURPOSE: An oral docetaxel formulation boosted by the Cytochrome P450 (CYP) 3 A inhibitor ritonavir, ModraDoc006/r, is currently under clinical investigation. Based on clinical data, the incidence of grade 1-2 diarrhea is increased with this oral docetaxel formulation compared to the conventional intravenous administration. Loperamide, a frequently used diarrhea inhibitor, could be added to the regimen as symptomatic treatment. However, loperamide is also a substrate of the CYP3A enzyme, which could result in competition between ritonavir and loperamide for this protein. Therefore, we were interested in the impact of coadministered loperamide on the pharmacokinetics of ritonavir-boosted oral docetaxel. METHODS: We administered loperamide simultaneously or with an 8-hour delay to humanized CYP3A4 mice (with expression in liver and intestine) receiving oral ritonavir and docetaxel. Concentrations of docetaxel, ritonavir, loperamide and two of its active metabolites were measured. RESULTS: The plasma exposure (AUC and Cmax) of docetaxel was not altered during loperamide treatment, nor were the ritonavir plasma pharmacokinetics. However, the hepatic and intestinal dispositions of ritonavir were somewhat changed in the simultaneous, but not 8-hour loperamide treatment groups, possibly due to loperamide-induced delayed drug absorption. The pharmacokinetics of loperamide itself did not seem to be influenced by ritonavir. CONCLUSION: These results suggest that delayed loperamide administration can be added to ritonavir-boosted oral docetaxel treatment, without affecting the overall systemic exposure of docetaxel.

The ABCB1 and ABCG2 efflux transporters limit brain disposition of the SYK inhibitors entospletinib and lanraplenib.

The highly selective Spleen Tyrosine Kinase (SYK) inhibitors entospletinib and lanraplenib disrupt kinase activity and inhibit immune cell functions. They are developed for treatment of B-cell malignancies and autoimmunity diseases. The impact of P-gp/ABCB1 and BCRP/ABCG2 efflux transporters, OATP1a/1b uptake transporters and CYP3A drug-metabolizing enzymes on the oral pharmacokinetics of these drugs was assessed using mouse models. Entospletinib and lanraplenib were orally administered simultaneously at moderate dosages (10 mg/kg each) to female mice to assess the possibility of examining two structurally and mechanistically similar drugs at the same time, while reducing the number of experimental animals and sample-processing workload. The plasma pharmacokinetics of both drugs were not substantially restricted by Abcb1 or Abcg2. The brain-to-plasma ratios of entospletinib in Abcb1a/b-/-, Abcg2-/- and Abcb1a/b;Abcg2-/- mice were 1.7-, 1.8- and 2.9-fold higher, respectively, compared to those in wild-type mice. For lanraplenib these brain-to-plasma ratios were 3.0-, 1.3- and 10.4-fold higher, respectively. This transporter-mediated restriction of brain penetration for both drugs could be almost fully inhibited by coadministration of the dual ABCB1/ABCG2 inhibitor elacridar, without signs of acute toxicity. Oatp1a/b and human CYP3A4 did not seem to affect the pharmacokinetics of entospletinib and lanraplenib, but mouse Cyp3a may limit lanraplenib plasma exposure. Unexpectedly, entospletinib and lanraplenib increased each other's plasma exposure by 2.6- to 2.9-fold, indicating a significant drug-drug interaction. This interaction was, however, unlikely to be mediated through any of the studied transporters or CYP3A. The obtained insights may perhaps help to further improve the safety and efficacy of entospletinib and lanraplenib.

Outcomes of cell infusion for the treatment of neurological sequelae induced by spinal anesthesia-associated subdural hematoma: A case report.

Background: Subdural hematoma following spinal anesthesia for cesarean delivery is a rare complication. Surgical removal of the hematoma is the standard treatment. However, there are still many patients who suffer permanent nerve damage of varying degrees after surgery. Cell therapy has recently shown great potential for treating nerve damage. Case presentation: This report described a case of paraplegia due to an epidural hematoma occurring after spinal anesthesia for cesarean section. The patient underwent surgery to remove the hematoma and rehabilitation afterward. However, no improvement was noted. Paralysis of the lower extremities associated with urinary retention and constipation persisted. The patient received three administrations of cell infusion: the first time with autologous bone marrow-derived mononuclear cells and the following two with autologous adipose mesenchymal/stromal cells. After three cell infusions, the patient was able to walk and could urinate and defecate voluntarily. Sensory and motor function were improved and MRI showed a decrease in adherence of the nerve roots and spinal cord. Conclusions: Our results demonstrated that cell therapy may ameliorate paralysis of the lower extremities as well as fecal and urinary function following spinal hematoma associated with spinal anesthesia.

Impact of tissue factor expression and administration routes on thrombosis development induced by mesenchymal stem/stromal cell infusions: re-evaluating the dogma.

BACKGROUND: Hyperactive coagulation might cause dangerous complications such as portal vein thrombosis and pulmonary embolism after mesenchymal stem/stromal cell (MSC) therapy. Tissue factor (TF), an initiator of the extrinsic coagulation pathway, has been suggested as a predictor of this process. METHODS: The expression of TF and other pro- and anticoagulant genes was analyzed in xeno- and serum-free manufactured MSCs. Furthermore, culture factors affecting its expression in MSCs were investigated. Finally, coagulation tests of fibrinogen, D-dimer, aPPTs, PTs, and TTs were measured in patient serum after umbilical cord (UC)-MSC infusions to challenge a potential connection between TF expression and MSC-induced coagulant activity.  RESULTS: Xeno- and serum-free cultured adipose tissue and UC-derived MSCs expressed the highest level of TF, followed by those from dental pulp, and the lowest expression was observed in MSCs of bone marrow origin. Environmental factors such as cell density, hypoxia, and inflammation impact TF expression, so in vitro analysis might fail to reflect their in vivo behaviors. MSCs also expressed heterogeneous levels of the coagulant factor COL1A1 and surface phosphatidylserine and anticoagulant factors TFPI and PTGIR. MSCs of diverse origins induced fibrin clots in healthy plasma that were partially suppressed by an anti-TF inhibitory monoclonal antibody. Furthermore, human umbilical vein endothelial cells exhibited coagulant activity in vitro despite their negative expression of TF and COL1A1. Patients receiving intravenous UC-MSC infusion exhibited a transient increase in D-dimer serum concentration, while this remained stable in the group with intrathecal infusion. There was no correlation between TF expression and D-dimer or other coagulation indicators. CONCLUSIONS: The study suggests that TF cannot be used as a solid biomarker to predict MSC-induced hypercoagulation. Local administration, prophylactic intervention with anticoagulation drugs, and monitoring of coagulation indicators are useful to prevent thrombogenic events in patients receiving MSCs. Trial registration NCT05292625. Registered March 23, 2022, retrospectively registered, https://www. CLINICALTRIALS: gov/ct2/show/NCT05292625?term=NCT05292625&draw=2&rank=1 . NCT04919135. Registered June 9, 2021, https://www. CLINICALTRIALS: gov/ct2/show/NCT04919135?term=NCT04919135&draw=2&rank=1 .

Reference Values for Inward Displacement in the Normal Left Ventricle: A Novel Method of Regional Left Ventricular Function Assessment.

BACKGROUND: Regional functional left ventricular (LV) assessment using current imaging techniques remains limited. Inward displacement (InD) has been developed as a novel technique to assess regional LV function via measurement of the regional displacement of the LV endocardial border across each of the 17 LV segments. Currently, normal ranges for InD are not available for clinical use. The aim of this study was to validate the normal reference limits of InD in healthy adults across all LV segments. METHODS: InD was analyzed in 120 healthy subjects with a normal LV ejection fraction, using the three standard long-axis views obtained during cardiac MRI that quantified the degree of inward endocardial wall motion towards the true LV center of contraction. For all LV segments, InD was measured in mm and expressed as a percentage of the theoretical degree of maximal segment contraction towards the true LV centerline. The arithmetic average InD was obtained for each of the 17 segments. The LV was divided into three regions, obtaining average InD at the LV base (segments 1-6), mid-cavity (segments 7-12) and apex (segments 13-17). RESULTS: Average InD was 33.4 ± 4.3%. InD was higher in basal and mid-cavity LV segments (32.8 ± 4.1% and 38.1 ± 5.8%) compared to apical LV segments (28.6 ± 7.7%). Interobserver variability correlations for InD were strong (R = 0.80, p < 0.0001). CONCLUSIONS: We provide clinically meaningful reference ranges for InD in subjects with normal LV function, which will emerge as an important screening and assessment imaging tool for a range of HFrEF therapies.

Unleashing the power of boron: enhancing nitrogen reduction reaction through defective ReS2 monolayers.

Density functional theory (DFT) calculations were utilized to investigate the electrocatalytic potential of single boron (B) atom doping in defective ReS2 monolayers as an active site. Our investigation revealed that B-doped defective ReS2, containing S and S-Re-S defects, demonstrated remarkable conductivity, and emerged as an exceptionally active catalyst for nitrogen reduction reactions (NRR), exhibiting limiting potentials of 0.63 and 0.53 V, respectively. For both cases, we determined the potential by examining the hydrogenation of adsorbed N2* to N2H*. Although the competing hydrogen evolution reaction (HER) process appeared dominant in the S-Re-S defect case, its impact was minimal. The outstanding NRR performance can be ascribed to the robust chemical interactions between B and N atoms. The adsorption of N2 on B weakens the N-N bond, thereby facilitating the formation of NH3. Moreover, we verified the selectivity and stability of the catalysts for NRR. Our findings indicate that B-doped defective ReS2 monolayers hold considerable promise for electrocatalysis in a variety of applications.

Simulation of GHz ultrasonic wave piezoelectric instrumentation for Fourier transform computation.

The recent emerging alternative to classic numerical Fast Fourier transform (FFT) computation, based on GHz ultrasonic waves generated from and detected by piezoelectric transducers for wavefront computing (WFC), is more efficient and energy-saving. In this paper, we present comprehensive studies on the modeling and simulation methods for ultrasonic WFC computation. We validate the design of the WFC system using ray-tracing, Fresnel diffraction (FD), and the full-wave finite element method (FEM). To effectively simulate the WFC system for inputs of 1-D signals and 2-D images, we verified the design parameters and focal length of an ideal plano-concave lens using the ray-tracing method. We also compared the analytical FFT solution with our Fourier transform (FT) results from 3-D and 2-D FD and novel 2-D full wave FEM simulations of a multi-level Fresnel lens with 1-D signals and 2-D images as inputs. Unlike the previously reported WFC system which catered only for 2-D images, our proposed method also can solve the 1-D FFT effectively. We validate our proposed 2-D full wave FEM simulation method by comparing our results with the theoretical FFT and Fresnel diffraction method. The FFT results from FD and FEM agree well with the digitally computed FFT, with computational complexity reduced from [Formula: see text] to O(N) for 2-D FFT, and from O(NlogN) to O(N) for 1-D FFT with a large number of signal sampling points N.

Solving ordinary and partial differential equations using an analog computing system based on ultrasonic metasurfaces.

Wave-based analog computing has recently emerged as a promising computing paradigm due to its potential for high computational efficiency and minimal crosstalk. Although low-frequency acoustic analog computing systems exist, their bulky size makes it difficult to integrate them into chips that are compatible with complementary metal-oxide semiconductors (CMOS). This research paper addresses this issue by introducing a compact analog computing system (ACS) that leverages the interactions between ultrasonic waves and metasurfaces to solve ordinary and partial differential equations. The results of our wave propagation simulations, conducted using MATLAB, demonstrate the high accuracy of the ACS in solving such differential equations. Our proposed device has the potential to enhance the prospects of wave-based analog computing systems as the supercomputers of tomorrow.

Highly Efficient Van Der Waals Heterojunction on Graphdiyne toward the High-Performance Photodetector.

Graphdiyne (GDY), a new 2D material, has recently proven excellent performance in photodetector applications due to its direct bandgap and high mobility. Different from the zero-gap of graphene, these preeminent properties made GDY emerge as a rising star for solving the bottleneck of graphene-based inefficient heterojunction. Herein, a highly effective graphdiyne/molybdenum (GDY/MoS2 ) type-II heterojunction in a charge separation is reported toward a high-performance photodetector. Characterized by robust electron repulsion of alkyne-rich skeleton, the GDY based junction facilitates the effective electron-hole pairs separation and transfer. This results in significant suppression of Auger recombination up to six times at the GDY/MoS2 interface compared with the pristine materials owing to an ultrafast hot hole transfer from MoS2 to GDY. GDY/MoS2 device demonstrates notable photovoltaic behavior with a short-circuit current of -1.3 × 10-5 A and a large open-circuit voltage of 0.23 V under visible irradiation. As a positive-charge-attracting magnet, under illumination, alkyne-rich framework induces positive photogating effect on the neighboring MoS2 , further enhancing photocurrent. Consequently, the device exhibits broadband detection (453-1064 nm) with a maximum responsivity of 78.5 A W-1 and a high speed of 50 µs. Results open up a new promising strategy using GDY toward effective junction for future optoelectronic applications.

The Correlation between Peripheral Blood Index and Immune Cell Expansion in Vietnamese Elderly Lung Cancer Patients.

(1) Background: The dysfunction and reduced proliferation of peripheral CD8+ T cells and natural killer (NK) cells have been observed in both aging and cancer patients, thereby challenging the adoption of immune cell therapy in these subjects. In this study, we evaluated the growth of these lymphocytes in elderly cancer patients and the correlation of peripheral blood (PB) indices to their expansion. (2) Method: This retrospective study included 15 lung cancer patients who underwent autologous NK cell and CD8+ T cell therapy between January 2016 and December 2019 and 10 healthy individuals. (3) Results: On average, CD8+ T lymphocytes and NK cells were able to be expanded about 500 times from the PB of elderly lung cancer subjects. Particularly, 95% of the expanded NK cells highly expressed the CD56 marker. The expansion of CD8+ T cells was inversely associated with the CD4+:CD8+ ratio and the frequency of PB-CD4+ T cells in PB. Likewise, the expansion of NK cells was inversely correlated with the frequency of PB-lymphocytes and the number of PB-CD8+ T cells. The growth of CD8+ T cells and NK cells was also inversely correlated with the percentage and number of PB-NK cells. (4) Conclusion: PB indices are intrinsically tied to immune cell health and could be leveraged to determine CD8 T and NK cell proliferation capacity for immune therapies in lung cancer patients.

Modular structures and the delivery of inpatient care in hospitals: a Network Science perspective on healthcare function and dysfunction.

BACKGROUND: Reinforced by the COVID-19 pandemic, the capacity of health systems to cope with increasing healthcare demands has been an abiding concern of both governments and the public. Health systems are made up from non-identical human and physical components interacting in diverse ways in varying locations. It is challenging to represent the function and dysfunction of such systems in a scientific manner. We describe a Network Science approach to that dilemma. General hospitals with large emergency caseloads are the resource intensive components of health systems. We propose that the care-delivery services in such entities are modular, and that their structure and function can be usefully analysed by contemporary Network Science. We explore that possibility in a study of Australian hospitals during 2019 and 2020. METHODS: We accessed monthly snapshots of whole of hospital administrative patient level data in two general hospitals during 2019 and 2020. We represented the organisations inpatient services as network graphs and explored their graph structural characteristics using the Louvain algorithm and other methods. We related graph topological features to aspects of observable function and dysfunction in the delivery of care. RESULTS: We constructed a series of whole of institution bipartite hospital graphs with clinical unit and labelled wards as nodes, and patients treated by units in particular wards as edges. Examples of the graphs are provided. Algorithmic identification of community structures confirmed the modular structure of the graphs. Their functional implications were readily identified by domain experts. Topological graph features could be related to functional and dysfunctional issues such as COVID-19 related service changes and levels of hospital congestion. DISCUSSION AND CONCLUSIONS: Contemporary Network Science is one of the fastest growing areas of current scientific and technical advance. Network Science confirms the modular nature of healthcare service structures. It holds considerable promise for understanding function and dysfunction in healthcare systems, and for reconceptualising issues such as hospital capacity in new and interesting ways.

Synthesis and Characterization of Novel Core-Shell ZnO@SiO2 Nanoparticles and Application in Antibiotic and Bacteria Removal.

A novel core-shell nanomaterial, ZnO@SiO2, based on rice husk for antibiotic and bacteria removal, was successfully fabricated. The ZnO@SiO2 nanoparticles were characterized by X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDX), Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), photoluminescence spectroscopy (PL), Brunauer-Emmett-Teller (BET) method, diffuse reflectance ultraviolet-vis (DR-UV-vis) spectroscopy, X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and ζ-potential measurements. ß-Lactam antibiotic amoxicillin (AMX) was removed using ZnO@SiO2 nanoparticles with an efficiency greater than 90%, while Escherichia coli removal was higher than 91%. The optimum effective conditions for AMX removal using ZnO@SiO2, including solution pH, adsorption time, and ZnO@SiO2 dosage, were 8, 90 min, and 25 mg/mL, respectively. The maximum adsorption capacity reached 52.1 mg/g, much higher than those for other adsorbents. Adsorption isotherms of AMX on ZnO@SiO2 were more in accordance with the Freundlich model than the Langmuir model. The electrostatic attraction between negative species of AMX and the positively charged ZnO@SiO2 surface induced adsorption, while the removal of E. coli was governed by both electrostatic and hydrophobic interactions. Our study demonstrates that ZnO@SiO2 based on rice husk is a useful core-shell nanomaterial for antibiotic and bacteria removal from water.

A new mode of luminescence in lanthanide oxalates metal-organic frameworks.

Two lanthanide metal-organic frameworks [Ln-MOFs, Ln = Eu(III), Tb(III)] composed of oxalic acid and Ln building units were hydrothermally synthesized and fully characterized by powder X-ray diffraction, Fourier-transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscope, and energy-dispersive X-ray spectroscopy. Furthermore, their magnetic susceptibility measurements were obtained using SQUID based vibrating sample magnetometer (MPMS 3, Quantum Design). Both Ln-MOFs exhibited highly efficient luminescent property. Solid-state photoluminescence (PL) measurements revealed phosphorescence emission bands of Eu-MOF and Tb-MOF centered at 618 nm (red emission) and 550 nm (green emission) upon excitation at 396 nm and 285 nm, respectively. Eu-MOF and Tb-MOF displayed a phosphorescence quantum yield of 53% and 40%, respectively. Time-resolved PL analyses showed very long lifetime values, at 600 and 1065 ± 1 µs for Eu-MOF and Tb-MOF, respectively. Calculations performed by density functional theory indicated a charge transfer form metal centres to the ligand which was in good agreement with the experimental studies. Therefore, this new mode of highly photoluminescent MOF materials is studied for the first time which paves the way for better understanding of these systems for potential applications.

A metalens-based analog computing system for ultrasonic Fourier transform calculations.

Wave-based analog computing is a new computing paradigm heralded as a potentially superior alternative to existing digital computers. Currently, there are optical and low-frequency acoustic analog Fourier transformers. However, the former suffers from phase retrieval issues, and the latter is too physically bulky for integration into CMOS-compatible chips. This paper presents a solution to these problems: the Ultrasonic Fourier Transform Analog Computing System (UFT-ACS), a metalens-based analog computer that utilizes ultrasonic waves to perform Fourier transform calculations. Through wave propagation simulations on MATLAB, the UFT-ACS has been shown to calculate the Fourier transform of various input functions with a high degree of accuracy. Moreover, the optimal selection of parameters through sufficient zero padding and appropriate truncation and bandlimiting to minimize errors is also discussed.

Evaluating the Safety and Quality of Life of Colorectal Cancer Patients Treated by Autologous Immune Enhancement Therapy (AIET) in Vinmec International Hospitals.

(1) Colorectal cancer (CRC) is an increasingly prevalent disease with a high mortality rate in recent years. Immune cell-based therapies have received massive attention among scientists, as they have been proven effective as low-toxicity treatments. This study evaluated the safety and effectiveness of autologous immune enhancement therapy (AIET) for CRC. (2) An open-label, single-group study, including twelve patients diagnosed with stages III and IV CRC, was conducted from January 2016 to December 2021. Twelve CRC patients received one to seven infusions of natural killer (NK)-cell and cytotoxic T-lymphocyte (CTL). Multivariate modelling was used to identify factors associated with health-related quality-of-life (HRQoL) scores. (3) After 20−21 days of culture, the NK cells increased 3535-fold, accounting for 85% of the cultured cell population. Likewise, CTLs accounted for 62.4% of the cultured cell population, which was a 1220-fold increase. Furthermore, the QoL improved with increased EORTC QLQ-C30 scores, decreased symptom severity, and reduced impairment in daily living caused by these symptoms (MDASI-GI report). Finally, a 14.3 ± 14.1-month increase in mean survival time was observed at study completion. (4) AIET demonstrated safety and improved survival time and HRQoL for CRC patients in Vietnam.

Unveiling the Protonation Kinetics-Dependent Selectivity in Nitrogen Electroreduction: Achieving 75.05 % Selectivity.

While higher selectivity of nitrogen reduction reaction (NRR) to ammonia (NH3 ) is always achieved in alkali, the selectivity dependence on nitrogen (N2 ) protonation and mechanisms therein are unrevealed. Herein, we profile how the NRR selectivity theoretically relies upon the first protonation that is collectively regulated by proton (H) abundance and adsorption-desorption, along with intermediate-*NNH formation. By incorporating electronic metal modulators (M=Co, Ni, Cu, Zn) in nitrogenase-imitated model-iron polysulfide (FeSx), a series of FeMSx catalysts with tailorable protonation kinetics are obtained. The key intermediates behaviors traced by in situ FT-IR and Raman spectroscopy and operando electrochemical impedance spectroscopy demonstrate the strong protonation kinetics-dependent selectivity that mathematically follows a log-linear Bradley curve. Strikingly, FeCuSx exhibits a record-high selectivity of 75.05 % at -0.1 V (vs. RHE) for NH3 production in 0.1 M KOH electrolyte.

Current Trends in Clinical Characteristics, Diagnosis, and Treatment of Polypoidal Choroidal Vasculopathy: A Perspective from Vietnam.

Polypoidal choroidal vasculopathy (PCV) is a common choroidal disease in the Asian population including Vietnam and is characterized by subretinal red-orange nodules, pigmented epithelium detachment, and massive subretinal hemorrhage. The recent focus on PCV in Vietnam can be attributed to advancements in PCV diagnosis and treatment. However, there is a scarcity of published literature and clinical data on PCV in the Vietnamese population, highlighting a key knowledge gap in this region. In order to address this gap, we gathered the opinions of experienced clinicians and retinal experts in Vietnam and reviewed available medical literature with the aim of: (i) providing an overview of PCV in the Vietnamese population-in terms of epidemiology, clinical characteristics, and management; (ii) tailoring international/national guidelines for the diagnosis and management of PCV, in line with available resources and medical equipment in Vietnam; and (iii) identifying gaps in clinical data in order to guide future PCV research in Vietnam and other countries with similar clinical conditions. The present review will enable healthcare providers and researchers to gain insight into current clinical practices and the limitations of PCV management in Vietnam and provide optimal and effective solutions.

Synthesis of a Selectively Nb-Doped WS2-MoS2 Lateral Heterostructure for a High-Detectivity PN Photodiode.

In this study, selective Nb doping (P-type) at the WS2 layer in a WS2-MoS2 lateral heterostructure via a chemical vapor deposition (CVD) method using a solution-phase precursor containing W, Mo, and Nb atoms is proposed. The different chemical activity reactivity (MoO3 > WO3 > Nb2O5) enable the separation of the growth temperature of intrinsic MoS2 to 700 °C (first grown inner layer) and Nb-doped WS2 to 800 °C (second grown outer layer). By controlling the Nb/(W+Nb) molar ratio in the solution precursor, the hole carrier density in the p-type WS2 layer is selectively controlled from approximately 1.87 × 107/cm2 at 1.5 at.% Nb to approximately 1.16 × 1013/cm2 at 8.1 at.% Nb, while the electron carrier density in n-type MoS2 shows negligible change with variation of the Nb molar ratio. As a result, the electrical behavior of the WS2-MoS2 heterostructure transforms from the N-N junction (0 at.% Nb) to the P-N junction (4.5 at.% Nb) and the P-N tunnel junction (8.1 at.% Nb). The band-to-band tunneling at the P-N tunnel junction (8.1 at.% Nb) is eliminated by applying negative gate bias, resulting in a maximum rectification ratio (105) and a minimum channel resistance (108 Ω). With this optimized photodiode (8.1 at.% Nb at Vg = -30 V), an Iphoto/Idark ratio of 6000 and a detectivity of 1.1 × 1014 Jones are achieved, which are approximately 20 and 3 times higher, respectively, than the previously reported highest values for CVD-grown transition-metal dichalcogenide P-N junctions.

HIV-1 gp120 Impairs Spatial Memory Through Cyclic AMP Response Element-Binding Protein.

HIV-associated neurocognitive disorders (HAND) remain an unsolved problem that persists despite using antiretroviral therapy. We have obtained data showing that HIV-gp120 protein contributes to neurodegeneration through metabolic reprogramming. This led to decreased ATP levels, lower mitochondrial DNA copy numbers, and loss of mitochondria cristae, all-important for mitochondrial biogenesis. gp120 protein also disrupted mitochondrial movement and synaptic plasticity. Searching for the mechanisms involved, we found that gp120 alters the cyclic AMP response element-binding protein (CREB) phosphorylation on serine residue 133 necessary for its function as a transcription factor. Since CREB regulates the promoters of PGC1α and BDNF genes, we found that CREB dephosphorylation causes PGC1α and BDNF loss of functions. The data was validated in vitro and in vivo. The negative effect of gp120 was alleviated in cells and animals in the presence of rolipram, an inhibitor of phosphodiesterase protein 4 (PDE4), restoring CREB phosphorylation. We concluded that HIV-gp120 protein contributes to HAND via inhibition of CREB protein function.