Endosomal Trafficking Bypassed by the RAB5B-CD109 Interplay Promotes Axonogenesis in KRAS-Mutant Pancreatic Cancer.

Perineural invasion (PNI) represents a unique biological feature associated with poor prognosis in pancreatic ductal adenocarcinoma (PDAC), especially in the presence of KRAS mutations. Extracellular vesicle (EV)-packaged circular RNAs (circRNAs) function as essential mediators of tumor microenvironment communication, triggering PDAC cell invasion and distant metastasis. However, the regulatory mechanisms of EV-packaged circRNAs in the PNI of KRAS-mutant PDAC have not yet been elucidated. Herein, a KRASG12D mutation-responsive EV-packaged circRNA, circPNIT, which positively correlated with PNI in PDAC patients is identified. Functionally, KRASG12D PDAC-derived EV-packaged circPNIT promoted axonogenesis and PNI both in vitro and in vivo. Mechanistically, the circPNIT-mediated Rab5B-CD109 interplay bypassed traditional endosomal trafficking to anchor Rab5B to the lipid rafts of multivesicular bodies and packaged circPNIT into CD109+ EVs. Subsequently, CD109+ EVs delivered circPNIT to neurons by binding to TRPV1 and facilitating DSCAML1 transcription-induced axonogenesis, which in turn enhanced the PNI by activating the GFRα1/RET pathway. Importantly, circPNIT-loaded CD109+ EVs are established to dramatically promote PNI in a KRASG12D/+ Trp53R172H/+ Pdx-1-Cre mouse model. Collectively, the findings highlight the mechanism underlying how EV-packaged circRNAs mediate the PNI of KRAS-mutant PDAC cells through the Rab5B endosomal bypass, identifying circPNIT as an effective target for the treatment of neuro-metastatic PDAC.

Bifunctional Ligand Passivation Enables Stable Blue Mixed-Halide CsPb(Br/Cl)3 Perovskite Quantum Dots toward Light-Emitting Diodes.

Mixed-halide CsPb(Br/Cl)3 perovskite quantum dots (PeQDs) have attracted extensive attention in light-emitting diodes (LEDs), but their low photoluminescent efficiency and especially poor stability impede their practical applications. Here, we employ bifunctional didodecyldimethylammonium thiocyanide (DDASCN) with a pseudohalogen SCN- and branched DDA+ to obtain blue-emitting CsPbBr2Cl PeQDs. DDASCN significantly boosts the photoluminescence quantum yield to 92% by inhibiting nonradiative recombination. Importantly, DDASCN PeQDs show excellent stabilities against air, UV light, heat, and polar solvents. These improved performances were explained by density functional theory calculation, which shows that SCN- fills the Cl- vacancy by simultaneously binding with undercoordinated Pb2+ and Cs+, while DDA+ connects undercoordinated Br- and lies parallel to the PeQD core, leading to efficient passivation and a strong binding capacity. Finally, we achieved high-performance white LEDs by integrating our PeQDs, resulting in a color-rendering index of 92.9, a color gamut of 119.61%, and chromaticity coordinates of (0.33, 0.33). This provides an effective method to obtain efficient and stable CsPb(Br/Cl)3 PeQDs for practical applications.

High-Entropy MXene as Bifunctional Mediator toward Advanced Li-S Full Batteries.

The development of high-energy-density Li-S batteries (LSBs) is still hindered by the disturbing polysulfide shuttle effect. Herein, with clever combination between "high entropy" and MXene, an HE-MXene doped graphene composite containing multiple element quasi-atoms as bifunctional mediator for separator modification (HE-MXene/G@PP) in LSBs is proposed. The HE-MXene/G@PP offers high electrical conductivity for fast lithium polysulfide (LiPS) redox conversion kinetics, abundant metal active sites for efficient chemisorption with LiPSs, and strong lipophilic characteristics for uniform Li+ deposition on lithium metal surface. As demonstrated by DFT theoretical calculations, in situ Raman, and DRT results successively, HE-MXene/G@PP efficiently captures LiPSs through synergistic modulation of the cocktail effect and accelerates the LiPSs redox reaction, and the lattice distortion effect effectively induces the homogeneous deposition of dendritic-free lithium. Therefore, this work achieves excellent long-term cycling performance with a decay rate of 0.026%/0.031% per cycle after 1200 cycles at 1 C/2 C. The Li||Li symmetric cell still maintains a stable overpotential after 6000 h under 40 mA cm-2/40 mAh cm-2. Furthermore, it delivers favorable cycling stability under 7.8 mg cm-2 and a low E/S ratio of 5.6 µL mg-1. This strategy provides a rational approach to resolve the sulfur cathode and lithium anode problems simultaneously.

In situ and General Multidentate Ligand Passivation Achieves Efficient and Ultra-Stable CsPbX3 Perovskite Quantum Dots for White Light-Emitting Diodes.

Inorganic CsPbX3 perovskite quantum dots (PeQDs) show great potential in white light-emitting diodes (WLEDs) due to excellent optoelectronic properties, but their practical application is hampered by low photoluminescence quantum yield (PLQY) and especially poor stability. Herein,  we developed an in-situ and general multidentate ligand passivation strategy that allows for CsPbX3 PeQDs not only near-unit PLQY, but significantly improved stability against storage, heat, and polar solvent. The enhanced optical property arises from high effectiveness of the multidentate ligand, diethylenetriaminepentaacetic acid (DTPA) with five carboxyl groups, in passivating uncoordinated Pb2+ defects and suppressing nonradiative recombination. First-principles calculations reveal that the excellent stability is attributed to tridentate binding mode of DTPA that remarkably boosts the adsorption capacity to PeQD core. Finally, combining the green and red PeQDs with blue chip,  we demonstrated highly luminous WLEDs with distinctly enhanced operation stability, a wide color gamut of 121.3% of national television system committee, standard white light of (0.33,0.33) in CIE 1931, and tunable color temperatures from warm to cold white light readily by emitters' ratio. This study provides an operando yet general approach to achieve efficient and stable PeQDs for WLEDs and accelerates their progress to commercialization.

Insight into Accelerating Polysulfides Redox Kinetics by BN@MXene Heterostructure for Li-S Batteries.

Sluggish redox kinetics and shuttle effect of polysulfides hinder the extensive application of the lithium-sulfur batteries (LSBs). Herein a functional heterostructure of boron nitride (BN) and MXene with an alternately layered structure (BN@MXene) is designed as separator interlayer. High efficiency Li+ transmission, uniform lithium deposition, strong adsorption, and efficient catalytic conversion activities of lithium polysulfides (LiPSs) realized by this heterostructure are confirmed by experiments and theoretical calculations. The alternately layered structure provides unblocked ion transmission channels and abundant active sites to accelerate the polysulfides redox kinetics with reduced energy barriers of oxidation and reduction reactions. As a result, the LSBs deliver an initial discharge capacity of up to 1273.9 mAh g-1 at 0.2 °C and a low decay of 0.058% per cycle in long-term cycling up to 700 cycles at 1 °C. This work provides an effective designing strategy to accelerate the polysulfides redox kinetics for advanced Li-S electrochemical system.

Capping Ligand Engineering Enables Stable CsPbBr3 Perovskite Quantum Dots toward White-Light-Emitting Diodes.

All-inorganic perovskite quantum dots (PeQDs) have sparked extensive research focus on white-light-emitting diodes (WLEDs), but stability and photoluminescence efficiency issues are still remain obstacles impeding their practical application. Here, we reported a facile one-step method to synthesize CsPbBr3 PeQDs at room temperature using branched didodecyldimethylammonium fluoride (DDAF) and short-chain-length octanoic acid as capping ligands. The obtained CsPbBr3 PeQDs have a near-unity photoluminescence quantum yield of 97% due to the effective passivation of DDAF. More importantly, they exhibit much improved stability against air, heat, and polar solvents, maintaining >70% of initial PL intensity. Making use of these excellent optoelectronic properties, WLEDs based on CsPbBr3 PeQDs, CsPbBr1.2I1.8 PeQDs, and blue LEDs were fabricated, which show a color gamut of 122.7% of the National Television System Committee standard, a luminous efficacy of 17.1 lm/W, with a color temperature of 5890 K, and CIE coordinates of (0.32, 0.35). These results indicate that the CsPbBr3 PeQDs have great practical potential in wide-color-gamut displays.

Aberrant expression of circular RNA DHPR facilitates tumor growth and metastasis by regulating the RASGEF1B/RAS/MAPK axis in hepatocellular carcinoma.

BACKGROUND: Circular RNAs (circRNAs) are noncoding RNAs. Accumulating evidence suggests that circRNAs play a critical role in human biological processes, especially tumorigenesis, and development. However, the exact mechanisms of action of circRNAs in hepatocellular carcinoma (HCC) remain unclear. METHODS: Bioinformatic tools and RT-qPCR were used to identify the role of circDHPR, a circRNA derived from the dihydropteridine reductase (DHPR) locus, in HCC and para-carcinoma tissues. Kaplan-Meier analysis and the Cox proportional hazard model were used to analyze the correlation between circDHPR expression and patient prognosis. Lentiviral vectors were used to establish stable circDHPR-overexpressing cells. In vitro and in vivo studies have shown that tumor proliferation and metastasis are affected by circDHPR. Mechanistic assays, including Western blotting, immunohistochemistry, dual-luciferase reporter assays, fluorescence in situ hybridization, and RNA immunoprecipitation, have demonstrated the molecular mechanism underlying circDHPR. RESULTS: CircDHPR was downregulated in HCC, and low circDHPR expression was associated with poor overall survival and disease-free survival rates. CircDHPR overexpression inhibits tumor growth and metastasis in vitro and in vivo. Further systematic studies revealed that circDHPR binds to miR-3194-5p, an upstream regulator of RASGEF1B. This endogenous competition suppresses the silencing effect of miR-3194-5p. We confirmed that circDHPR overexpression inhibited HCC growth and metastasis by sponging miR-3194-5p to upregulate the expression of RASGEF1B, which is regarded as a suppressor of the Ras/MAPK signaling pathway. CONCLUSIONS: Aberrant circDHPR expression leads to uncontrolled cell proliferation, tumorigenesis, and metastasis. CircDHPR may serve as a biomarker and therapeutic target for HCC.

[Priority ranking of Chinese patent medicine prescriptions for type 2 diabetes mellitus (syndrome of deficiency of both Qi and Yin): based on analytic hierarchy process (AHP)].

Clinical expertise, patient preference, and the best evidence are the three elements of evidence-based medicine. Based on high-level and high-quality evidence, qualitative and quantitative analysis of the prescribing decisions of physicians is beneficial to improving clinical efficacy. A mature methodological system is available for the retrieval, analysis, summary, evaluation, and recommendation of the evidence, but there are still few studies on physicians' prescribing decisions. How to analyze the trend of physicians' prescribing decisions based on the priority ranking in addition and subtraction of prescriptions? Analytic hierarchy process(AHP) is a method for decision making, which arranges the elements of the decision problem into overall goal, criteria, and operational sub-criteria, and uses the matrix eigenvector method to solve the problem. This study aims to analyze the priority of physicians' prescribing decisions for diabetes mellitus with deficiency of both Qi and Yin based on AHP. To be specific, a database of diabetes mellitus cases with deficiency of both Qi and Yin was established and AHP was used to yield the priority ranking of Chinese patent medicine prescriptions in specific clinical scenarios. In the selected cases of diabetes mellitus with deficiency of both Qi and Yin, Xiaoke Pills was the best prescription for the treatment of type 2 diabetes mellitus(deficiency of both Qi and Yin)(normalized=0.388), followed by Liuwei Dihuang Pills(normalized=0.269), Qishen Capsules(normalized=0.230), and Shengmai Injection(normalized=0.113). According to the analysis the available data, for type 2 diabetes mellitus(deficiency of both Qi and Yin), Xiaoke Pills was the most effective prescription in specific scenarios. When the physicians' prescribing decisions are consistent with the evidence, quantitative analysis of physicians' cognition will boost the evidence-based medical decision-making. However, the research results are also affected by the quality of literature, evidence level and priority, which are thus have some limitations. It is recommended that further small data research based on individual cases be carried out to lay a evidence-based basis for the clinical decision-making of type 2 diabetes mellitus.

Monolayer SnI2: An Excellent p-Type Thermoelectric Material with Ultralow Lattice Thermal Conductivity.

Using density functional theory and semiclassical Boltzmann transport equation, the lattice thermal conductivity and electronic transport performance of monolayer SnI2 were systematically investigated. The results show that its room temperature lattice thermal conductivities along the zigzag and armchair directions are as low as 0.33 and 0.19 W/mK, respectively. This is attributed to the strong anharmonicity, softened acoustic modes, and weak bonding interactions. Such values of the lattice thermal conductivity are lower than those of other famous two-dimensional thermoelectric materials such as MoO3, SnSe, and KAgSe. The two quasi-degenerate band valleys for the valence band maximum make it a p-type thermoelectric material. Due to its ultralow lattice thermal conductivities, coupled with an ultrahigh Seebeck coefficient, monolayer SnI2 possesses an ultrahigh figure of merits at 800 K, approaching 4.01 and 3.34 along the armchair and zigzag directions, respectively. The results indicate that monolayer SnI2 is a promising low-dimensional thermoelectric system, and would stimulate further theoretical and experimental investigations of metal halides as thermoelectric materials.

Low thermal conductivity and high performance anisotropic thermoelectric properties of XSe (X = Cu, Ag, Au) monolayers.

Combining density functional theory (DFT) and semi-classic Boltzmann transport theory, we report the thermoelectric (TE) performance of a family of two-dimensional (2D) group IB-selenides XSe (X = Cu, Ag, Au). The results show that these monolayers exhibit small and anisotropic phonon velocities (0.98-3.84 km s-1), large Grüneisen parameters (up to 100), and drastic phonon scattering between the optical and acoustic phonons. These intrinsic properties originate from strong phonon anharmonicity and suppress the heat transport capacity, resulting in low lattice thermal conductivities (12.54 and 1.22 W m-1 K-1) along the x- and y-directions for a CuSe monolayer. Among our studied monolayers, the 2D CuSe monolayer possesses the most remarkable TE performance with ultrahigh ZT (3.26) for n-type doping along the y-direction at 300 K. CuSe monolayer can achieve higher thermoelectric conversion efficiency at a lower synthetic preparation cost than the expensive AgSe and AuSe monolayers, and our work provides a theoretical basis for paving the way for further experimental studies.

DeepHBV: a deep learning model to predict hepatitis B virus (HBV) integration sites.

BACKGROUND: The hepatitis B virus (HBV) is one of the main causes of viral hepatitis and liver cancer. HBV integration is one of the key steps in the virus-promoted malignant transformation. RESULTS: An attention-based deep learning model, DeepHBV, was developed to predict HBV integration sites. By learning local genomic features automatically, DeepHBV was trained and tested using HBV integration site data from the dsVIS database. Initially, DeepHBV showed an AUROC of 0.6363 and an AUPR of 0.5471 for the dataset. The integration of genomic features of repeat peaks and TCGA Pan-Cancer peaks significantly improved model performance, with AUROCs of 0.8378 and 0.9430 and AUPRs of 0.7535 and 0.9310, respectively. The transcription factor binding sites (TFBS) were significantly enriched near the genomic positions that were considered. The binding sites of the AR-halfsite, Arnt, Atf1, bHLHE40, bHLHE41, BMAL1, CLOCK, c-Myc, COUP-TFII, E2A, EBF1, Erra, and Foxo3 were highlighted by DeepHBV in both the dsVIS and VISDB datasets, revealing a novel integration preference for HBV. CONCLUSIONS: DeepHBV is a useful tool for predicting HBV integration sites, revealing novel insights into HBV integration-related carcinogenesis.

Case Report: One-Year Delay in the Effect of Conversion Surgery Therapy for Advanced Hepatocellular Carcinoma After Systemic Therapy.

Hepatocellular carcinoma (HCC) is the sixth most commonly diagnosed malignancy and the third leading cause of cancer-related deaths worldwide. A 58-year-old man visited his local hospital due to abdominal discomfort and was diagnosed with lung metastasis. After admission to our hospital in April 2020, he received two cycles of transcatheter arterial embolization (TAE), hepatic arterial infusion chemotherapy (HAIC-Folfox), sorafenib, and camrelizumab every 3 weeks. Due to the end of HAIC treatment, he underwent drug-eluting transcatheter arterial chemoembolization (dTACE) once, sorafenib, and camrelizumab. However, because of worsening liver function, we interrupted TACE and only gave sorafenib and camrelizumab in August 2020. Although he received systemic therapy, the tumors still rapidly progressed and we considered the possibility of tumor resistance. Subsequently, regorafenib was given. In September, the patient underwent conventional TACE (cTACE) once, regorafenib, and camrelizumab. After half a year of comprehensive treatment, the treatment effect was not satisfactory, and he returned to the local hospital to received regorafenib every day and camrelizumab once every 3 weeks. The patient found that the tumor and lung metastasis had shrunk significantly after 1 year of the initial diagnosis, then he was admitted to our hospital and received surgery treatment, and now he has survived disease-free for 6 months.