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Liver failure is a lethal condition with hepatocellular dysfunction, and liver transplantation is presently the only effective treatment. However, due to the limited availability of donors and the potential immune rejection, novel therapeutic strategies are actively sought to restore the normal hepatic architectures and functions, especially for livers with inherited metabolic dysfunctions or chronic diseases. Although the conventional cell therapy has shown promising results, the direct infusion of hepatocytes is hampered by limited hepatocyte sources, poor cell viability, and engraftment. Hence, this review mainly highlights the role of stem cells and progenitors as the alternative cell source and summarizes the potential approaches based on tissue engineering to improve the delivery efficiency of cells. Particularly, the underlying mechanisms for cell therapy using stem cells and progenitors are discussed in two main aspects: paracrine effect and cell differentiation. Moreover, tissue-engineering approaches using cell aggregates and decellularized liver scaffolds for bioengineering of functional hepatic constructs are discussed and compared in terms of the potential to replicate liver physiological structures. In the end, a potentially effective strategy combining the premium advantages of stem cell aggregates and decellularized liver scaffolds is proposed as the future direction of liver tissue engineering and regeneration. [ABSTRACT FROM AUTHOR]

Targeting the activated epidermal growth factor receptor (EGFR) via clustered regularly interspaced short palindromic repeat (CRISPR) technology is appealing to overcome the drug resistance of hepatocellular carcinoma (HCC) towards tyrosine kinase inhibitor (TKI) therapy. However, combining these two distinct drugs using traditional liposomes results in a suboptimal synergistic anti-HCC effect due to the limited CRISPR/Cas9 delivery efficiency caused by lysosomal entrapment after endocytosis. Herein, we developed a liver-targeting gene-hybridizing-TKI fusogenic liposome (LIGHTFUL) that can achieve high CRISPR/Cas9 expression to reverse the EGFR-mediated drug resistance for enhanced TKI-based HCC therapy efficiently. Coated with a galactose-modified membrane-fusogenic lipid layer, LIGHTFUL reached the targeting liver site to fuse with HCC tumor cells, directly and efficiently transporting interior CDK5- and PLK1-targeting CRISPR/Cas9 plasmids (pXG333-CPs) into the HCC cell cytoplasm and then the cell nucleus for efficient expression. Such membrane-fusion-mediated pXG333-CP delivery resulted in effective downregulation of both CDK5 and PLK1, sufficiently inactivating EGFR to improve the anti-HCC effects of the co-delivered TKI, lenvatinib. This membrane-fusion-participant codelivery strategy optimized the synergetic effect of CRISPR/Cas9 and TKI combinational therapy as indicated by the 0.35 combination index in vitro and the dramatic reduction of subcutaneous and orthotopic TKI-insensitive HCC tumor growth in mice. Therefore, the established LIGHTFUL provides a unique co-delivery platform to combine gene editing and TKI therapies for enhanced synergetic therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Highlights: This review focuses on the therapeutic mechanisms, targeting strategies of various nanomaterials in acute liver failure, and recent advances of diverse nanomaterials for acute liver failure therapy, diagnosis, and imaging. This review provides an outlook on the applications of nanomaterials, especially on the new horizons in acute liver failure therapy, and inspires broader interests across various disciplines. Acute liver failure (ALF), a fatal clinical disease featured with overwhelming hepatocyte necrosis, is a grand challenge in global health. However, a satisfactory therapeutic option for curing ALF is still absent, other than liver transplantation. Nanobiomaterials are currently being developed for the diagnosis and treatment of ALF. The liver can sequester most of nanoparticles from blood circulation, which becomes an intrinsic superiority for nanobiomaterials targeting hepatic diseases. Nanobiomaterials can enhance the bioavailability of free drugs, thereby significantly improving the therapeutic effects in ALF. Nanobiomaterials can also increase the liver accumulation of therapeutic agents and enable more effective targeting of the liver or specific liver cells. In addition, stimuli-responsive, optical, or magnetic nanomaterials exhibit great potential in the therapeutical, diagnostic, and imaging applications in ALF. Therefore, therapeutic agents in combination with nanobiomaterials increase the specificity of ALF therapy, diminish adverse systemic effects, and offer a multifunctional theranostic platform. Nanobiomaterial holds excellent significance and prospects in ALF theranostics. In this review, we summarize the therapeutic mechanisms and targeting strategies of various nanobiomaterials in ALF. We highlight recent developments of diverse nanomedicines for ALF therapy, diagnosis, and imaging. Furthermore, the challenges and future perspectives in the theranostics of ALF are also discussed. [ABSTRACT FROM AUTHOR]

Liver failure is a lethal condition with hepatocellular dysfunction, and liver transplantation is presently the only effective treatment. However, due to the limited availability of donors and the potential immune rejection, novel therapeutic strategies are actively sought to restore the normal hepatic architectures and functions, especially for livers with inherited metabolic dysfunctions or chronic diseases. Although the conventional cell therapy has shown promising results, the direct infusion of hepatocytes is hampered by limited hepatocyte sources, poor cell viability, and engraftment. Hence, this review mainly highlights the role of stem cells and progenitors as the alternative cell source and summarizes the potential approaches based on tissue engineering to improve the delivery efficiency of cells. Particularly, the underlying mechanisms for cell therapy using stem cells and progenitors are discussed in two main aspects: paracrine effect and cell differentiation. Moreover, tissue-engineering approaches using cell aggregates and decellularized liver scaffolds for bioengineering of functional hepatic constructs are discussed and compared in terms of the potential to replicate liver physiological structures. In the end, a potentially effective strategy combining the premium advantages of stem cell aggregates and decellularized liver scaffolds is proposed as the future direction of liver tissue engineering and regeneration. [ABSTRACT FROM AUTHOR]

Light is a particularly appealing tool for on‐demand drug delivery due to its noninvasive nature, ease of application, and exquisite temporal and spatial control. Great progress is achieved in the development of novel light‐driven drug delivery strategies with both breadth and depth. Light‐controlled drug delivery platforms can be generally categorized into three groups: photochemical, photothermal, and photoisomerization‐mediated therapies. Various advanced materials, such as metal nanoparticles, metal sulfides and oxides, metal–organic frameworks, carbon nanomaterials, upconversion nanoparticles, semiconductor nanoparticles, stimuli‐responsive micelles, polymer‐ and liposome‐based nanoparticles are applied for light‐stimulated drug delivery. In view of the increasing interest in on‐demand targeted drug delivery, the development of light‐responsive systems with a focus on recent advances, key limitations, and future directions is reviewed. [ABSTRACT FROM AUTHOR]

The human gut is important for food digestion and absorption, as well as a venue for a large number of microorganisms that coexist with the host. Although numerous in vitro models have been proposed to study intestinal pathology or interactions between intestinal microbes and host, they are far from recapitulating the real intestinal microenvironment in vivo. To assist researchers in further understanding gut physiology, the intestinal microbiome, and disease processes, a novel technology primarily based on microfluidics and cell biology, called "gut-on-chip," was developed to simulate the structure, function, and microenvironment of the human gut. In this review, we first introduce various types of gut-on-chip systems, then highlight their applications in drug pharmacokinetics, host–gut microbiota crosstalk, and nutrition metabolism. Finally, we discuss challenges in this field and prospects for better understanding interactions between intestinal flora and human hosts, and then provide guidance for clinical treatment of related diseases. [ABSTRACT FROM AUTHOR]

Bacterial therapy, which presents a smart platform for delivering and producing therapeutic agents, as monotherapy or in combination with other therapeutic modes, has provided a breakthrough for the treatment of a range of diseases. The integration of synthetic biology technology with bacteria enables their characteristics like chemotaxis and biomolecule secretion to outperform conventional diagnostics and therapeutics, thereby facilitating their clinical applications in a range of diseases. Compared to injection-administered bacteria, orally-delivered bacteria improve patient compliance while avoiding the risk of systemic infections. However, oral administration of microbes always leads to a substantial loss of viability due to the highly acidic environment in the stomach and bile salt in the intestine. Thus, the formulation of these bacteria into microcapsules using appropriate biomaterials is a promising approach for reducing cell death during gastrointestinal passage and controlling the release of these therapeutic cells across the intestinal tract. In this review, we reveal the basic principles of oral bacterial delivery, from internal genetic engineering approaches to external encapsulation and modification, and summarize the most recent biomedical applications. Finally, we discuss future trends in oral bacterial therapy as well as current challenges that need to be resolved to advance their clinical applications. Oral administration of bacterial therapeutics has gained attractive attention recently for the treatment of a variety of diseases according to the close associations between bacteria and the hosts. This review provides an overview of orally-administrated bacterial therapy, summarizes their most recent biomedical applications, and discusses potential future applications as well as existing challenges. Unlabelled Image • Oral administration of bacterial therapeutics is limited by their biocompatibility, stability, and efficiency in vivo. • How genetic circuits and genetic engineering technologies to enable bacterial characteristics to outperform conventional diagnostics and therapeutics will be introduced. • The choice of biomaterials and technologies for therapeutic bacteria encapsulation is closely related to the improved efficiency of oral bacterial delivery. [ABSTRACT FROM AUTHOR]

To improve the clinical diagnosis of neural autoimmune diseases, we developed an in-house muscle-specific kinase (MuSK) antibody cell-based assay (CBA) and compared its performance with RIA, ELISA, and other CBAs. Sera from patients with myasthenia gravis (MG) and other autoimmune diseases were analyzed. We found 46 (18.3%) MuSK-CBA Ab positive cases among 251 AChR-Ab negative cases [patients] and 4 (0.6%) MuSK-CBA Ab positive cases [among] the 624 AChR-Ab positive samples. Comparing these with available clinic assays, our highly specific CBA method is more sensitive than commercial ELISA and IFA(indirect immunofluorescence assay). Unlabelled Image • MuSK-CBA better represents the conformation-dependent epitope of MuSK. • The in-house MuSK-CBA is more sensitive than commercial ELISA and IFA. • CBA could be masked by the presence of antinuclear antibodies. [ABSTRACT FROM AUTHOR]

α-In2Se3 has attracted increasing attention in recent years due to its excellent electrical and optical properties. Especially, attention has been paid to its peculiar ferroelectric and piezoelectric properties which most other two-dimensional (2D) materials do not possess. This paper presents the first measurement of the thickness-dependent band gaps of few-layer α-In2Se3 by electron energy loss spectroscopy (EELS). The band gap increases with decreasing film thickness which varies from 1.44 eV in a 48 nm thick area to 1.64 eV in an 8 nm thick area of the samples. Further, by combining the improved exchange-correlation potential and proper screening of the internal electric field in an advanced 2D electronic structure technique, we have been able to obtain the structural dependence of the band gap within density functional theory up to hundreds of atoms. This is also the first calculation of a similar type for 2D ferroelectric materials. Both experiment and theory suggest that the variation of the band gap of α-In2Se3 fits well with the quantum confinement model for 2D materials. [ABSTRACT FROM AUTHOR]

In this work, 2D-layered Ti 3 C 2 /TiO 2 hybrids derived from Ti 3 C 2 MXenes were calcined at different temperature for 2 h with a ramping rate of 5 °C/min to adjust the electromagnetic wave absorption performance, and the static dielectric properties of the Ti 3 C 2 and anatase TiO 2 were studied by density functional theory calculations to illustrate the contribution to dielectric loss of TiO 2 and Ti 3 C 2 MXenes. The 2D-layered Ti 3 C 2 /TiO 2 Hybrids exhibit a minimum reflection loss of −40.07 dB at 19.2 GHz with a relative thin thickness of 1.1 mm, and the effective bandwidth with reflection loss less than −10 dB reaches more than 3.6 GHz. The calculated results display higher ε ' and ε ' ' of Ti 3 C 2 MXenes than that of anatase TiO 2 in the measured range of frequency, which is in accordance with the experiments. The 2D-layered Ti 3 C 2 /TiO 2 hybrids are expected to exhibit the enhanced electromagnetic wave absorption performance thanks to the appropriate complex permittivity, matching impendence and high dielectric loss. [ABSTRACT FROM AUTHOR]

The room-temperature coercivity of the hot-deformed magnet increased from 1.21 to 1.86 T and the coercivity at 180°C increased from 0.33 to 0.70 T by adding 8 wt.% Nd 60 Fe 15 Ga 20 Cu 5 alloy powders. The temperature coefficient of coercivity increased from −0.469 to −0.402%/°C and is superior to that of most magnets. The microstructure revealed that the Nd 2 Fe 14 B grains were isolated by Nd-Ga-Cu-rich intergranular phases. Statistical analysis indicated that the average grain size was reduced by approximately 25%. Both the exchange decoupling between grains and the ultrafine grains were responsible for the improved thermal stability of the magnets without using heavy rare-earth elements. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Background Human papillomavirus (HPV) causes anogenital warts and cancers in men and women. However, little is known about sex differences regarding the natural history of anogenital HPV infection. Methods Starting in May 2014, an observational cohort study including 2309 men and 2378 women aged 18–55 years was conducted in Liuzhou, China. Samples from anogenital sites were tested for HPV genotypes by multicolor real-time polymerase chain reaction and melting curve analysis biannually for ~1 year. Results The incidence of oncogenic HPV infection was similar in men and women (10.3 and 11.5/1000 person-months; P =.275), whereas the incidence of HPV-6/11 infection was higher in men than in women (2.0 vs 1.1; P =.018). The incidence of both oncogenic HPV and HPV-6/11 infections was significantly higher in women in the 18- to 25-year age group than in the older age groups (P =.006 and.011, respectively), whereas it did not vary by age among men (P =.552 and.425, respectively). Additionally, men were more likely than women to clear oncogenic infections (101.5 vs 58.6/1000 person-months; P <.001), but no significant difference was found in the clearance of HPV-6/11 by sex (111.7 vs 84.8; P =.266). The median time to clearance of oncogenic type and type 6/11 infections was not age dependent for either sex (all P >.05). Conclusions The natural history of oncogenic and nononcogenic HPV infection differs by sex, which implies that sex-specific vaccination strategies should be considered for oncogenic and nononcogenic HPV. Clinical Trials Registration NCT02188004. [ABSTRACT FROM AUTHOR]

The human gut is important for food digestion and absorption, as well as a venue for a large number of microorganisms that coexist with the host. Although numerous in vitro models have been proposed to study intestinal pathology or interactions between intestinal microbes and host, they are far from recapitulating the real intestinal microenvironment in vivo. To assist researchers in further understanding gut physiology, the intestinal microbiome, and disease processes, a novel technology primarily based on microfluidics and cell biology, called "gut-on-chip," was developed to simulate the structure, function, and microenvironment of the human gut. In this review, we first introduce various types of gut-on-chip systems, then highlight their applications in drug pharmacokinetics, host–gut microbiota crosstalk, and nutrition metabolism. Finally, we discuss challenges in this field and prospects for better understanding interactions between intestinal flora and human hosts, and then provide guidance for clinical treatment of related diseases. [ABSTRACT FROM AUTHOR]

Aim: Myeloid differentiation factor 88 (MyD88) plays a key role in tumor proliferation and metastasis. Targeting MyD88 is a potent strategy in tumor therapy. TJ‐M2010‐5 is a small molecule derivative of aminothiazole and could inhibit dimer formation of MyD88. To explore the potential of TJ‐M2010‐5 in tumor therapy, we determined its antitumor effect and correlate mechanisms of TJ‐M2010‐5 in hepatocellular carcinoma (HCC). Methods: The antitumor effect of intratumoral injection of TJ‐M2010‐5 to H22 tumor‐bearing BALB/c mice was observed. Tumor growth was monitored. The expression of MyD88 and Ki‐67 were detected by immunofluorescence. In vitro, the impacts of TJ‐M2010‐5 on proliferation, cell cycle, necrosis, and apoptosis of H22 cells were evaluated. The direct and indirect effects of TJ‐M2010‐5 on macrophages were evaluated using flow cytometry. Results: TJ‐M2010‐5 induced both G0/G1 and G1/S phase arrests in HCC cells. Mechanically, downstream activation of MyD88 was suppressed by TJ‐M2010‐5 through the extracellular regulated protein kinase‐1/2/p90 ribosomal S6 kinase/glycogen synthase kinase‐3β signaling pathway. In turn, cyclin‐dependent kinase (CDK)6/cyclin D1 and CDK2/cyclin E complexes were downregulated. More importantly, TJ‐M2010‐5 significantly inhibited tumor growth in mice. Additionally, the portion of antitumor M1 macrophages (F4/80+CD11c+) in the tumor microenvironment were increased after TJ‐M2010‐5 treatment. Together, these data indicate that TJ‐M2010‐5 is a promising therapeutic drug for HCC. Conclusions: These results indicate that MyD88 is a feasible target for antitumor treatment and TJ‐M2010‐5 is a qualified candidate for HCC therapy. [ABSTRACT FROM AUTHOR]

Background: Knowledge of human papillomavirus (HPV) transmission dynamics, which have important public health implications for designing HPV vaccination strategies, is scarce in undeveloped areas.Methods: From May to July 2014, 390 couples were enrolled from the general population in Liuzhou, China. Exfoliated cells from male penis shaft/glans penis/coronary sulcus (PGC) and perianal/anal canal (PA) sites and from female vaginal, vulvar, and PA sites were collected biannually for 1 year.Results: The HPV type-specific concordance rate between couples was 15.5% (95% confidence interval [CI], 8.5%-25.0%). For anogenital HPV transmission, the male-to-female transmission rate (11.5 [95% CI, 4.3-30.7] per 1000 person-months) was similar to the female-to-male transmission rate (11.3 [95% CI, 5.9-21.7] per 1000 person-months). The concordance rates between male PGC site and female vaginal, vulvar, and PA sites were 20.0%, 21.8%, and 14.9%, respectively, which were significantly higher than expected by chance. Infections transmitted from males to females seemed mainly originated from male genital sites, whereas for female-to-male transmission, the vaginal, vulvar, and PA sites might be all involved.Conclusions: Among the heterosexual couples with relatively conservative sexual behavior, the anogenital HPV transmission rate for females to males is similar to that of males to females. In addition to the vagina and vulva, the female PA site is also an important reservoir for HPV transmission. [ABSTRACT FROM AUTHOR]

Sandwich-Structured Implants to Obstruct Multipath Energy Supply and Trigger Self-Enhanced Hypoxia-Initiated Chemotherapy Against Postsurgical Tumor Recurrence and Metastasis (Adv. Sci. 22/2023) The postsurgical adjuvant treatment with combretastatin A4 phosphate and tirapazamineloaded implants efficiently inhibits tumor recurrence and metastasis, showing great potential for clinical applications. B Postsurgical Tumor Therapy with In Situ Implantation b In article number 2300899, Yanteng Xu, Zhaohui Tang, Yu Tao, Mingqiang Li, and co-workers report an implantable sandwich-structured dual-drug depot to achieve self-enhanced postsurgical tumor treatment through starvation therapy and hypoxia-induced chemotherapy that are triggered in sequence. [Extracted from the article]

Novel pH responsive copolymers with tertiary amine groups were prepared by free radical polymerization with 2-(dialkylamino)ethyl methacrylate monomers. These polymers were pH sensitive with the ability to be responsively fine-tuned in aqueous solution, which was proven through titration, transmittance measurements, and proton nuclear magnetic resonance spectroscopy. The polymers were soluble in water at low pH values, induced by electrostatic repulsion between amine groups, and aggregated above their pKa value due to the hydrophobic effect of the alkyls. The pH responsive values were precisely tuned from 7.4 to 4.8 by increasing the hydrophobic monomer ratio. Our work provides a novel approach for the development of ultrasensitive pH-responsive polymers for application in biomedical materials. [ABSTRACT FROM AUTHOR]

Abstract Non-alcoholic fatty liver disease (NAFLD) is always characterized by hepatic steatosis and insulin resistance. Dysregulated long noncoding RNAs regulate pathogenesis of NAFLD. However, the role of Mirt2 (long noncoding RNA myocardial infraction associated transcript 2) in NAFLD remains unclear. This original study aims to investigate the role of Mirt2 in hepatic steatosis and insulin resistance. Mirt2 was decreased in the livers of high-fat diet (HFD) mice, Ob / Ob , Db / Db , and fasting mice. Hepatic Mirt2 restoration attenuated hyperglycemia, insulin resistance and steatosis in the livers of obese mice, and Mirt2 inhibition promoted fasting hyperglycemia and lipid droplets accumulation in normal mouse livers. Furthermore, overexpression of Mirt2 resulted in suppression of miR-34a-5p , whereas knockdown of Mirt2 exerted opposite effects in the livers. Then, miR-34a-5p was a positive regulator of NAFLD by targeting USP10 , which serves as a negative regulator of NAFLD. Overexpression of Mirt2 made miR-34a-5p mimic fail to reduce luciferase activity of USP10 3′-UTR, and this regulation was also demonstrated by Western blot. Similarly, overexpression of miR-34a-5p significantly let Mirt2 lost the ability to elevate USP10 protein level. Thus, Mirt2 can function as the sponge of miR-34a-5p. Moreover, Mirt2 -mediated upregulation of USP10 protein expression can be reversed by silencing USP10. USP10 inhibition could abolish Mirt2 overexpression-induced suppression of glucose production and lipogenesis in hepatocytes. In conclusion, the decrease of Mirt2 expression contributed to hepatic insulin resistance and steatosis in obese mice, and Mirt2 / miR-34a-5p / USP10 was involved in NAFLD development. Overexpression of Mirt 2 might be a promising strategy for treatment of NAFLD. Highlights • Mirt2 was decreased in livers of obese mice and fasting mice. • Mirt2 overexpression improved and knockdown of Mirt2 promoted insulin sensitivity, fatty liver in HFD mice. • Mirt2 increased USP10 expression by regulating miR-34a-5p/USP10 axis during gluconeogenesis/lipogenesis. [ABSTRACT FROM AUTHOR]

Local anesthetics are a class of drugs, which have wide applications in the treatment of acute and chronic pain. However, their analgesic effects only last for a few hours because of their short half-life, which is insufficient for clinical application, especially for long-term surgery or postoperative analgesia. Herein, an injectable hydrogel/microsphere (GEL/MS) composite co-encapsulating bupivacaine (BUP) and dexmedetomidine (DEX) was developed for effective sustained analgesia. The GEL/MS composite appeared as a three-dimensional porous network microstructure and displayed sustained sequential release of DEX and BUP over several days in vitro , without obvious burst release. In this composite, DEX was released from the GEL matrix preferentially, exhibited long-term vasoconstriction effect and improved the local anesthetic concentration at injection site by preventing BUP from diffusing into the blood circulation. BUP was released subsequently from the MS for blockage of the Na + channel on nerve cell membranes and provided long-term analgesia. In vivo analgesic effect demonstrated that DEX significantly prolonged the effect of analgesia when synergistically administered with BUP in the GEL/MS composite. Moreover, the GEL/MS composite exhibited good biodegradability and biocompatibility in histological analyses. Taken together, the administration of BUP and DEX in the GEL/MS composite achieved a synergistic effect in prolonging analgesia without causing toxicity, and thus represented a potential strategy for long-acting analgesia therapy. [ABSTRACT FROM AUTHOR]

The coalescence of a pair of sub-holes forms a V-type intersecting hole for pressure atomizer nozzles. This design makes use of the internal impact effect to promote the breakup of liquid jets, enhancing liquid-gas mixing. To clarify the physical structure of the in- and near nozzle flow field for the V-type intersecting hole atomizer nozzles, high speed photography was employed to visualize the in-orifice and near field flow behaviors of four atomizer nozzles, three of which were V-type intersecting hole nozzles with impact angle varied from 30° to 50°, and the other one was a cylindrical hole nozzle as a reference. In-nozzle flow and jet images in both the intersecting plane and its axial normal plane were captured. The results show that the use of V-type intersecting holes in an atomizer nozzle eliminates the generation of cavitation inside the nozzle orifices even under the conditions of strong hydraulic flip for the reference nozzle, leading to 15%–50% higher discharge coefficients than those of the reference nozzle, and yields fan-shaped jets, which least and most disperse at the intersecting plane and its axial normal plane, respectively. Furthermore, these fan-shaped jets demonstrate superior radial dispersion, in terms of 1–5 times larger normalized cross sectional areas than those of the reference nozzle. Moreover, increasing the impact angle enhances the internal impact effect, resulting in wider spreading angles and larger cross sectional areas of the jets, however, lower discharge coefficients. [ABSTRACT FROM AUTHOR]

Sb 2 S 3 has a unique one-dimensional structure-composed (Sb 4 S 6) n ribbons leads to strong anisotropic carrier transport characteristic: carrier transport along the (Sb 4 S 6) n ribbon is more efficient than other ribbons. Therefore, it's crucial to control the direction of grain growth along the (hk1) orientation. In this work, the close space sublimation method was utilized to fabricate Sb 2 S 3 thin films with a systematic al regulation of substrate temperature. The results demonstrate that optimized Sb 2 S 3 thin film presented preferred orientation at the direction of (hk1). The champion device based on Au and Ni electrodes achieved a power conversion efficiency (PCE) of 3.06% and 1.69%, respectively. Schematic diagram of the close space sublimation system. [Display omitted] • The (hk1)-oriented Sb 2 S 3 thin films were prepared by close space sublimation method. • Study of the effect of different substrate temperatures on the structure and morphology of Sb 2 S 3 thin films. • Solar cells with structure of FTO/TiO 2 /CdS/Sb 2 S 3 /Ni were fabricated. • Ni was firstly used as the electrode for Sb 2 S 3 solar cells. [ABSTRACT FROM AUTHOR]

Magnetic nanoparticles (NPs) have emerged as a promising tool for suicide gene therapy. However, the separate delivery of the suicide gene and prodrug in current systems limits their clinical translation. Therefore, improving magnetically mediated suicide gene therapy by exploring higher performance magnetic NP-based hybrid nanoplatforms is an important challenge. In the current study, shape-controlled magnetic mesoporous silica nanoparticles (M-MSNs) were prepared, and their performance in magnetic resonance imaging (MRI)-guided, magnetically targeted and hyperthermia-enhanced suicide gene therapy of hepatocellular carcinoma (HCC) was investigated. Compared with sphere-like MSNs, rod-like MSNs exhibited higher loading capacity, faster prodrug release behavior, stronger magnetically enhanced gene delivery and better magnetic hyperthermia properties. Utilizing the improved magnetic properties of the M-MSNs allowed us to demonstrate highly effective dual magnetically enhanced suicide gene therapy in vivo with decreased systematic toxicity and with the ability to monitor therapeutic outcome by MRI. Because of their magnetic targeting abilities, magnetic hyperthermia performance and MRI properties, these M-MSNs might prove to be a potentially superior candidate for suicide gene therapy of HCC. [ABSTRACT FROM AUTHOR]

With explosive growth in fingerprint databases, Automatic Fingerprint Identification System has become more challenging than ever. Consequently, it is necessary to develop a fast and exact fingerprint indexing to meet the efficiency and accuracy. In this paper, learning Compact Binary Minutia Cylinder Code (CBMCC) is proposed as an effective and discriminative feature representation and Multi-Index Hashing (MIH) is suitably adopted to accelerate the exact search in fingerprint indexing field for the first time. Firstly, we analyze Minutia Cylinder Code to find that it is strongly bit-correlated and awfully unbalanced. Accordingly, we propose an optimization model to learn CBMCC with the balanced independent property and the minimal binary quantization loss. Finally, MIH method further speeds up the exact search in Hamming space by building multiple hash tables on binary code substrings. The performance test shows that CBMCC is effective and discriminative as it has the maximum intra-bit variance while the minimum inter-bit correlation. Furthermore, numerous experiments on public databases demonstrate that CBMCC–MIH is quite outstanding for fingerprint indexing since it achieves an extremely small error rate with a fairly low penetration rate. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract A foundation of the modern technology that uses single-crystal silicon has been the growth of high-quality single-crystal Si ingots with diameters up to 12 inches or larger. For many applications of graphene, large-area high-quality (ideally of single-crystal) material will be enabling. Since the first growth on copper foil a decade ago, inch-sized single-crystal graphene has been achieved. We present here the growth, in 20 min, of a graphene film of (5 × 50) cm2 dimension with >99% ultra-highly oriented grains. This growth was achieved by: (1) synthesis of metre-sized single-crystal Cu(1 1 1) foil as substrate; (2) epitaxial growth of graphene islands on the Cu(1 1 1) surface; (3) seamless merging of such graphene islands into a graphene film with high single crystallinity and (4) the ultrafast growth of graphene film. These achievements were realized by a temperature-gradient-driven annealing technique to produce single-crystal Cu(1 1 1) from industrial polycrystalline Cu foil and the marvellous effects of a continuous oxygen supply from an adjacent oxide. The as-synthesized graphene film, with very few misoriented grains (if any), has a mobility up to ∼23,000 cm2 V−1 s−1 at 4 K and room temperature sheet resistance of ∼230 Ω/□. It is very likely that this approach can be scaled up to achieve exceptionally large and high-quality graphene films with single crystallinity, and thus realize various industrial-level applications at a low cost. [ABSTRACT FROM AUTHOR]

[Display omitted] Poly(L-glutamic acid)- g -methoxy poly(ethylene glycol)/Combretastatin A4 (CA4)/BLZ945 nanoparticles (CB-NPs) have shown great potential in synergistic cancer therapy. However, it is still unclear how the nanoparticles' formula, such as injection dose, active agent ratio, and drug loading content, affects the side effects and in vivo efficacy of CB-NPs. In this study, a series of CB-NPs with different BLZ945/CA4 (B/C) ratios and drug loading contents were synthesized and evaluated on a hepatoma (H22) tumor-bearing mice model. The injection dose and B/C ratio were found to have a significant influence on the in vivo anticancer efficacy. The CB-NPs 20 with B/C weight ratio of 0.45/1, and total drug loading content (B + C) of 20.7 wt%, showed the highest potential for clinical application. Systematic pharmacokinetics, biodistribution, and in vivo efficacy evaluation for CB-NPs 20 have been finished, which may provide significant instruction for medicine screening and clinical application. [ABSTRACT FROM AUTHOR]

Engineering hepatocytes as multicellular cell spheroids can improve their viability after implantation in vivo for effective rescue of the devastating acute liver failure (ALF). However, there is still a lack of straightforward methods for efficient generation of functional hepatocyte spheroids. In this study, a magnetic system, consisting of magnetic microwell arrays and magnet blocks, is developed to realize magnetically controlled 3D cell capture and spatial confinement-mediated cell aggregation. The cell spheroids with smaller size show superior hepatic functions than the larger-sized counterparts. Notably, the intrinsic magnetism of magnetic microwell arrays can regulate superoxide anions in hepatocyte spheroids and herein promote various biological processes, including antioxidation, hepatocyte-related functions, and pro-angiogenic potential. Ectopic implantation of the functional cell spheroids in ALF-challenged mice significantly prolongs the animal survival, ameliorates inflammation, and promotes liver regeneration. Hence, application of the magnetic system for generation of functionally enhanced hepatocyte spheroids holds great potential for clinical translation in the future. [ABSTRACT FROM AUTHOR]

Keywords: CRISPR/Cas9; gene editing; hepatitis B virus (HBV); liver-specific promoters; magnetic nanosystems EN CRISPR/Cas9 gene editing hepatitis B virus (HBV) liver-specific promoters magnetic nanosystems 1 1 1 02/13/23 20230209 NES 230209 B Spatiotemporal Liver Genome Editing b In article number 2210860, Mingqiang Li, Yu Tao, Yeh-Hsing Lao, and co-workers report spatiotemporally-controlled gene editing to inactivate hepatitis B infection based on magnetic nanoparticles and liver-specific promoter-driven CRISPR/Cas9 plasmid. CRISPR/Cas9, gene editing, hepatitis B virus (HBV), liver-specific promoters, magnetic nanosystems Magnetic-Activated Nanosystem with Liver-Specific CRISPR Nonviral Vector to Achieve Spatiotemporal Liver Genome Editing as Hepatitis B Therapeutics (Adv. Funct. [Extracted from the article]

[Display omitted] • Excessive accumulation of reactive oxygen species (ROS) is involved in acute myocardial infarction (AMI)-related pathological processes and vascular reperfusion therapy injury. • Alpha lipoic acid (LA) exhibits excellent antioxidant properties, but cannot converge locally to scavenge ROS after oral or intravenous administration. • We used poly(lactic- co -glycolic) (PLGA) copolymers as carriers to form a thin film morphology (LA@PLGA) via electrospinning technology to achieve controlled release of LA. • The application of LA@PLGA showed anti-oxidative activity and anti-apoptosis effect in vitro, as well as improved heart functions and reduced cardiac fibrosis in vivo. Oxidative stress, characterized by excessive accumulation of reactive oxygen species (ROS), is involved in acute myocardial infarction (AMI)-related pathological processes and vascular reperfusion therapy injury. Alpha lipoic acid (LA) exhibits excellent antioxidant properties, however, its application is limited by inherent characteristics, including rapid clearance and extensive volume distribution. In this study, we hypothesized that scavenging cardiac ROS using adequately delivered LA could promote heart repair. Here, we report a new strategy for dynamic-release LA to treat AMI disease. In particular, this involves using poly(lactic- co -glycolic) (PLGA) copolymers as carriers to form a thin film (LA@PLGA) via electrospinning technology to achieve controlled release of LA, which essentially blocking local ROS production in damaged hearts. The drug-loading capacity and capsulation efficiency of this compound film could be regulated by determining the dose proportions of LA and PLGA. The incubation of LA@PLGA showed strong anti-oxidative activity and anti-apoptosis effect in hydrogen peroxide–administered primary cardiomyocytes. Patching LA@PLGA on the infarcted cardiac surfaces of AMI mice dramatically improved heart functions and reduced cardiac fibrosis throughout ventricular remodeling process. Importantly, the attenuation of detrimental pathologies was observed, including oxidative stress, senescence, DNA damage, cytokine-related processes, apoptosis, and ferroptosis. These results suggest that PLGA-carried LA can reduce ROS damage and restore heart function after myocardial damage, demonstrating a great potential for LA drugs in treating AMI disease. [ABSTRACT FROM AUTHOR]

Tumor-positive resection margins after surgery can result in tumor recurrence and metastasis. Although adjuvant postoperative radiotherapy and chemotherapy have been adopted in clinical practice, they lack efficacy and result in unavoidable side effects. Herein, a self-intensified in-situ therapy approach using electrospun fibers loaded with a biomimetic nanozyme and doxorubicin (DOX) is developed. The fabricated PEG-coated zeolite imidazole framework-67 (PZIF67) is demonstrated as a versatile nanozyme triggering reactions in cancer cells based on endogenous H 2 O 2 and •O 2 −. The PZIF67-generated •OH induces reactive oxygen species (ROS) overload, implementing chemodynamic therapy (CDT). The O 2 produced by PZIF67 inhibits the expression of hypoxia-up-regulated proteins, thereby suppressing tumor progression. PZIF67 also catalyzes the degradation of glutathione, further disturbing the intracellular redox homeostasis and enhancing CDT. Furthermore, the introduced DOX not only kills cancer cells individually, but also replenishes the continuously consumed substrates for PZIF67-catalyzed reactions. The PZIF67-weakened drug resistance strengthens the cytotoxicity of DOX. The combined application of PZIF67 and DOX also suppresses metastasis-associated genes. Both in vitro and in vivo results demonstrate that the self-intensified synergy of PZIF67 and DOX on electrospun fibers efficiently prevents postsurgical tumor recurrence and metastasis, offering a feasible therapeutic regimen for operable malignant tumors. [ABSTRACT FROM AUTHOR]

Berberine, an bioactive isoquinolin alkaloid from traditional Chinese herbs, is considered to be a promising agent based on its remarkable activity against hepatocellular carcinoma. However, the clinical application of this nature compound had been hampered owing to its properties such as poor aqueous solubility, low gastrointestinal absorption, and reduced bioavailability. Therefore, we developed Janus magnetic mesoporous silica nanoparticles (Fe3O4- mSiO2 NPs) consisting of a Fe3O4 head for magnetic targeting and a mesoporous SiO2 body for berberine delivery. A pH-sensitive group was introduced on the surface of mesoporous silica for berberine loading to develop a tumor microenvironment-responsive nanocarrier, which exhibited uniform morphology, good superparamagnetic properties, high drug-loading amounts, superior endocytic ability, and low cytotoxicity. Berberine-loaded Fe3O4- mSiO2 NPs exerted extraordinarily high specificity for hepatocellular carcinoma cells, which was due to the pH-responsive berberine release, as well as higher endocytosis capacity in hepatocellular carcinoma cells rather than normal liver cells. More importantly, an external magnetic field could significantly improve antitumor activity of Ber-loaded Fe3O4- mSiO2 NPs through enhancing berberine internalization. Taken together, our results suggest that Janus nanocarriers driven by the magnetic field may provide an effective and safe way to facilitate clinical use of berberine against hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Prostate cancer is one of the most prevalent malignancies among men. Although chemotherapy has been an effective therapeutic approach for treating metastatic prostate cancer, serious undesired side effects have hampered its wide application clinically. In this work, a pH-responsive LHRH-conjugated hydroxyethyl starch-doxorubicin (HES-DOX/LHRH) prodrug was facilely synthesized by conjugating oxidized HES (HES-CHO) with DOX and LHRH through an acid-sensitive Schiff base bond. The resulting prodrug spontaneously self-assembled into nanoscopic micelle with a radius of about 55 nm in an aqueous environment. HES-DOX/LHRH significantly improved the in vivo tissue distribution of the drug. Compared to its non-targeted counterpart, targeted HES-DOX/LHRH demonstrated a greater in vitro anti-proliferative capability toward mouse RM-1 prostate cells. More importantly, targeted HES-DOX/LHRH exhibited higher levels of anti-tumor and anti-metastasis activities against an RM-1-xenografted mouse model, with lower systemic toxicity compared to free DOX·HCl and non-targeted HES-DOX. Hence, these results revealed that targeted HES-DOX/LHRH possesses great potential application in clinical chemotherapy of metastatic prostate cancer. [ABSTRACT FROM AUTHOR]

The heterogeneity of shale pore structure is a vital problem that cannot be ignored in the process of shale oil exploration and development. The organic-rich laminated shale (ORLS) and organic-poor layered shale (OPLS) show significantly different pore system heterogeneity. In this study area, the porosity and permeability of ORLS (2.7% and 0.00053mD) are higher than those of OPLS (2.29% and 0.00041mD). The heterogeneity of the pore system in ORLS is reflected by the wider pore size range of intercrystalline pores (pore size of 0.002–5.5 μm), the stronger holistic distribution heterogeneity of intergranular pores (average △α of 1.61) and organic pores (average △f of 2.65) at local locations. The wider range and discontinuity of the pore size distribution for intergranular pores and organic pores, and the instability of the morphological structure for intercrystalline pores and microfractures, all lead to the heterogeneity of the pore system in OPLS. The micropore (<2 nm) volume and macropore (>50 nm) volume of ORLS are higher than that of OPLS, while the surface area and volume of mesopores (2–50 nm) are lower than those of OPLS. The macropore has the most obvious fractal characteristics and three fractal dimensions. The macropore volume of ORLS is positively correlated with reservoir physical and pore multifractal properties, while the mesopore volume of OPLS is positively correlated with reservoir properties and negatively correlated with fractal properties. Pore system evolution patterns of shale reservoirs are obviously controlled by the mineral composition, laminae, TOC content, thermal evolution degree and fluid pathways. The macropore volume in ORLS shows a clear positive correlation with the pyrite content. The high TOC content and high thermal evolution degree are more likely to produce erosive fluids. Laminar interfaces, microfractures and primary pores provide channels for the fluid migration. The development degree of secondary dissolution may be an important factor leading to the difference of reservoir qualities between ORLS and OPLS. • Pore structures of multi-type pores and multi-scale pores in the ORLS and OPLS have strong heterogeneity. • The integration of CGA, NGA, HPMI and fractals can characterize shale pores more finely. • The dominant pore volume is helpful to physical properties, while pore fractal shows dual effects. • The reservoir qualities of ORLS and OPLS are the function of five main controls. • ORLS and OPLS have different pore evolution patterns. [ABSTRACT FROM AUTHOR]

Malignant spinal tumors, categorized into primary and metastatic ones, are one of the most serious diseases due to their high morbidity and mortality rates. Common primary spinal tumors include chordoma, chondrosarcoma, osteosarcoma, Ewing’s sarcoma, and multiple myeloma. Spinal malignancies are not only locally invasive and destructive to adjacent structures, such as bone, neural, and vascular structures, but also disruptive to distant organs (e.g., lung). Current treatments for spinal malignancies, including wide resection, radiotherapy, and chemotherapy, have made significant progress like improving patients’ quality of life. Among them, chemotherapy plays an important role, but its potential for clinical application is limited by severe side effects and drug resistance. To ameliorate the current situation, various polymer nanoparticles have been developed as promising excipients to facilitate the effective treatment of spinal malignancies by utilizing their potent advantages, for example, targeting, stimuli response, and synergetic effect. This review overviews the development of polymer nanoparticles for antineoplastic delivery in the treatment of spinal malignancies and discusses future prospects of polymer nanoparticle-based treatment methods. [ABSTRACT FROM AUTHOR]

Breast cancer is the most prevalent malignancy and the first leading cause of cancer-related mortality among the female population worldwide. Approaches for precise and reliable detection of breast cancer cells, particularly in the nascent state, are desperately needed for elevating the survival rate of patients bearing the breast tumor. In this work, we successfully performed the sensitive, precise, and reliable breast cancer cell detection using facilely fabricated bovine serum albumin-gold nanocluster (BSA-AuNCs) protein corona stabilized, epithelial cell adhesion molecule (EpCAM) aptamer linked fluorescent polystyrene nanoparticle (PS NP), termed as PS-BSA-AuNCs-Apt. The rapidly adsorbed BSA-AuNCs hard protein corona without complicated covalent conjugation not only imparted excellent colloidal stability to the PS nanoparticles, but also offered numerous active anchors for the targeted EpCAM aptamers to locate. With the remarkable aid of the aptamers specifically targeting the EpCAM-positive breast cancer cells, the PS-BSA-AuNCs-Apt emitted strong and photostable dual-color fluorescent signals for precise and reliable cancer cell detection by overcoming the false signals. The specific identification potency of the PS-BSA-AuNCs-Apt system was further verified by successfully detecting the xenografted breast tumor tissue. Notably, to the best of our knowledge, the protein corona formed nanoprobes was exploited for direct tumor cell and tissue detection with high efficacy for the first time, demonstrating their promising potential in clinical tumor detection. [Display omitted] [ABSTRACT FROM AUTHOR]

• Both artemisinin-piperaquine and artemether-lumefantrine maintained high efficacy during the treatment of falciparum malaria in Grande Comore island. • Artemisinin-piperaquine in combination with anti-gametocyte treatment is recommended for rapidly increasing the killing effect of the malaria gametocyte in areas with a high rate of carrying. • Asymptomatic parasitaemia infections bring new challenges for malaria control in Comoros. Malaria significantly rebounded in 2018 in the Comoros; this created an urgent need to conduct clinical trials to investigate the effectiveness of artemisinin and its derivatives. An open-label, non-randomised controlled trial of artemisinin-piperaquine (AP) and artemether-lumefantrine (AL) was conducted in Grande Comore island from June 2019 to January 2020. A total of 238 uncomplicated falciparum malaria cases were enrolled and divided 1:1 into two treatments. The primary endpoint was the 42-day adequate clinical and parasitological responses (ACPR). Secondary endpoints were parasitaemia and fever clearance at day 3, gametocytes and tolerability. The 42-day ACPR before and after PCR correction were 91.43% (95% CI 83.93–95.76%) and 98.06% (95% CI 92.48–99.66%) for AP treatment, respectively, and 96.00% (95% CI 88.17–98.14%) and 98.97% (95% CI 93.58–99.95%) for AL treatment, respectively. Complete clearance of the parasitaemia and fever for both groups was detected on day 3. Gametocytes disappeared on day 21 in the AP group and on day 2 in AL group. Specifically, the adverse reactions were mild in both groups. It was found that AP and AL maintained their high efficacy and tolerance in the Comoros. Nonetheless, asymptomatic malaria infections bring new challenges to malaria control. [ABSTRACT FROM AUTHOR]

Neuropathic pain (NP) is one of the most intractable diseases. The lack of effective therapeutic measures remains a major problem due to the poor understanding of the cause of NP. The aim of the present study was to investigate the effect of the long non-coding RNA small nucleolar RNA host gene 5 (SNHG5) in NP and the underlying molecular mechanism in order to identify possible therapeutic targets. A chronic constriction injury (CCI) mouse model was used to investigate whether SNHG5 prevents NP and the inflammatory response. Luciferase and RNA pull-down assays were used to detect the binding between SNHG5 and miR-142-5p as well as between miR-142-5p and CAMK2A. Western blot and qPCR were used to detect the RNA and protein expression. The results indicated that SNHG5 significantly inhibited CCI-induced NP. In addition, SNHG5 inhibited the inflammatory response through decreasing the release and the mRNA expression of interleukin (IL)-1β, IL-6, IL-10 and tumor necrosis factor-α. Mechanistically, SNHG5 acted via sponging microRNA-142-5p, thereby upregulating the expression of calcium/calmodulin-dependent protein kinase II α (CAMK2A). Further investigation indicated that CAMK2A knockdown also inhibited CCI-induced NP and inflammation. In summary, the present study demonstrated that SNHG5 silencing could alleviate the neuropathic pain induced by chronic constriction injury via sponging miR-142-5p and regulating the expression of CAMK2A. [ABSTRACT FROM AUTHOR]

Since hepatitis B virus (HBV) infection can cause chronic viral hepatitis, increase the risk of liver fibrosis and cirrhosis, and ultimately result in hepatoma, it is of great significance to explore convenient, rapid, and sensitive diagnostic strategies for HBV DNA detection. In this study, we developed a novel and sensitive fluorescent biosensor for HBV detection based on the sensing system consisting of CRISPR-Cas12a enzymes and metal nanoclusters as the luminescent nanoprobes, involving gold nanoclusters (AuNCs), silver nanoclusters (AgNCs), and copper nanoclusters (CuNCs). The DNA probes could effectively be applied as the template for the preparation of fluorescent metal nanoclusters. In the presence of the HBV target, the trans-cleavage capability of Cas12a was able to be initiated to degrade DNA probes, which brought about the inhibition of metal nanoclusters formation, thereby giving minimal fluorescence signals. In comparison with AuNCs and AgNCs, the CuNCs-based nanosensor exhibited much higher sensitivity. In addition, the fluorescence response of CuNCs to HBV detection was significantly faster, which could be completed within 25 min without the requirements of sophisticated equipment or harsh reaction conditions. Moreover, the practical application of this analysis method was also demonstrated to detect HBV DNA target in human serum samples with satisfactory recovery, which was promising for simple, rapid, sensitive, and label-free HBV DNA bioanalysis. • The biosensor for HBV DNA detection consisting of CRISPR-Cas12a and metal nanoclusters is developed. • Different metal (gold, silver, and copper) nanoclusters have been applied as the luminescent nanoprobes. • The sensing platform allows rapid DNA detection within 25 min with high sensitivity and selectivity. [ABSTRACT FROM AUTHOR]

The Ahe Formation is one of the significant hydrocarbon units in the Kuqa Depression of Tarim Basin, which is characterized by poor reservoir quality and strong heterogeneities due to the diagenetic effects. Thus, 'diagenetic facies' are introduced to explore high-quality reservoir layers. According to the reservoir spaces, main diagenetic minerals and diagenesis, four types of diagenetic facies are categorized: tightly compacted facies, dissolution facies, carbonated cemented facies and microfracture facies. Petrophysical characteristics of different diagenetic facies are summarized, which shows that the dissolution facies and microfracture facies have higher porosities, permeabilities and bigger pore radii. Logging characteristics indicate that logging values of four diagenetic facies are overlapped seriously, making it impossible to classify them by original logging crossplot. Principal component analysis (PCA), linear discriminant analysis (LDA) and back propagation neural networks (BPNN) are used to build diagenetic facies identification models, and the former two belong to the linear statistical algorithms, while the latter is a nonlinear algorithm. By comparing the identification accuracy of these three algorithms, principal components (PCs) crossplot cannot recognize diagenetic facies effectively. LDA can achieve automatic identification by establishing discriminant functions, but its identification accuracy (71.7%) is too low to satisfy the exploration requirements. However, the trained BPNN yield 80% accuracy, which is more advantageous than PCA and LDA. The blind test shows that the predicted results by trained BPNN have a very high coincidence with the thin section analysis and the logging interpretation results. Therefore, the BPNN as provided in this paper can be effectively used for diagenetic facies identification based on conventional well logs. • Four types of diagenetic facies are identified in the tight sandstone reservoirs of the Ahe Formation. • Principal component analysis (PCA), linear discriminant analysis (LDA) and back propagation neural network (BPNN) are used to recognize diagenetic facies. • The trained BPNN model is selected to recognize favorable diagenetic facies at a field-scale. [ABSTRACT FROM AUTHOR]

The synthesis of polymer–drug conjugate (PDC) capable of convenient preparation and controlled release of therapeutic agents is still an urgent requirement in drug delivery field. Herein, we develop a novel anti-cancer PDC engineered with side groups of disulfide and ester bonds for on-demand delivery of paclitaxel (PTX) with redox and pH dual sensitive behaviors. A simple polymer, 3,3′-dithiodipropionic acid functionalized poly(ethylene glycol)- b -poly( l -lysine) (mPEG- b -P(LL-DTPA)), was synthesized and PTX was directly conjugated to the carboxyl groups of mPEG- b -P(LL-DTPA) to obtain the disulfide-containing polymer–PTX conjugate (P(L-SS-PTX)). Another structural similar polymer–PTX conjugate without disulfide bonds (P(L-PTX)) was also prepared to verify the function of disulfide linkages. The P(L-SS-PTX) micelles showed rapid drug release under tumor-relevant reductive conditions as designed. Interestingly, the PTX release from P(L-SS-PTX) micelles could also be promoted by the increased acidity (pH ≈ 5). In vitro cytotoxicity study showed that the P(L-SS-PTX) micelles exhibited significantly enhanced cytotoxicity against a variety of tumor cells compared to the non-sensitive P(L-PTX) micelles. The in vivo studies on B16F1 melanoma bearing C57BL/6 mice demonstrated the superior antitumor activity of P(L-SS-PTX) over both free PTX and P(L-PTX). This dual-sensitive prodrug provides a useful strategy for anti-tumor drug delivery. [ABSTRACT FROM AUTHOR]

ABSTRACT: Early and accurate diagnosis of viruses is critical for control of the pandemic. CRISPR/Cas-based detection of nucleic acid is an emerging technology for molecular diagnostics, and has been applied for virus detection. Though these methods have excellent sensitivity and specificity, most of them were not able to measure the quantity of virus. We here developed a droplet digital reverse transcription loop-mediated isothermal amplification (R T-LAMP) e nhanced C as12b-based RNA d etection platform (RECD), for quantitative detection of viral RNA. CRISPR/Cas12b, which is more thermally stable than other family members in CRISPR systems, is combined with digital RT-LAMP. Due to the innate characteristic of digital format detection and CRISPR/Cas system, droplet digital RECD (ddRECD) assay enables absolute quantification of viral RNA, with single-molecule sensitivity. We expect the ddRECD assay will be a powerful tool for molecular diagnostics. [Display omitted] • It is a warm-start reaction in a homogeneous reaction system that prevents premature target amplification. • It enables absolute quantification of target RNA with single-molecule sensitivity. • The innate character of CRISPR/Cas12b enables the ddRECD excellent specificity. • It could be performed in isothermal condition, that does not need additional temperature control or complex devices. [ABSTRACT FROM AUTHOR]

Abstract: There are two important obstacles for the currently applied anti-cancer drug delivery systems. One is the conflict between long-circulation and cellular uptake while the other one is the achievement of ideal anti-cancer efficacy. To solve these problems, we designed a polypeptide-based micelle system that combined the advantages of receptor mediated endocytosis and multi-drug delivery. Firstly, an amphiphilic PLG-g-Ve/PEG graft copolymer was prepared by grafting α-tocopherol (Ve) and polyethylene glycol (PEG) to poly(l-glutamic acid) (PLG). Then docetaxel (DTX) and cisplatin (CDDP) were co-loaded into the PLG-g-Ve/PEG micelles via hydrophobic and chelation effect. After that, the surface of the dual-drug-loaded micelles was decorated with an αvβ3 integrin targeting peptide c(RGDfK). The targeted dual-drug-loaded micelles showed synergistic cytotoxicity and enhanced internalization rate in mouse melanoma (B16F1) cells. In vivo tests demonstrated that remarkable long circulation, anti-tumor and anti-metastasis efficacy could be achieved using this drug delivery system. This work revealed a strategy for the design and preparation of anti-cancer drug delivery systems with reduced side effect, enhanced anti-tumor and anti-metastasis efficacy. [Copyright &y& Elsevier]

Objectives: Acceptability of pre-exposure prophylaxis (PrEP) and willingness to participate in a clinical trial for both safety and efficacy of PrEP were investigated among female sex workers (FSWs) in Guangxi, China. Methods: A cross-sectional study was performed in three cities in Guangxi. Structured, self-administered questionnaires were used to assess the acceptability of PrEP and the willingness to participate in a clinical trial. Multivariable logistic regression models were fitted to identify predictors. Results: Among 405 participants, 15.1% had heard of PrEP. If PrEP was deemed to be effective, safe and provided for free, 85.9% reported that they would accept it, and 54.3% of those who accepted PrEP said that they would participate in a clinical trial. The increased acceptability of PrEP was associated with working in male dominated venues, higher income, a poor family relationship, better HIV/AIDS knowledge, not realizing HIV risk from unfamiliar clients, not being forced to use condoms by the gatekeepers, consistent use of condoms, and use of drugs to prevent STD infection. The increased willingness to participate in a clinical trial was associated with a poor family relationship, better HIV/AIDS knowledge, not realizing HIV risk from unfamiliar clients, a willingness to adhere to daily PreP use, and not being concerned about discrimination by others. The main reason for rejecting PrEP or participating in a clinical trial was the concern about the side effects of PrEP. Conclusions: Acceptability of PrEP among Guangxi FSWs is relatively high, indicating that PrEP intervention programs may be feasible for Chinese FSWs. Given the fact that most of the participants had never heard of PrEP before, and that family, gatekeepers, and social discrimination could significantly affect its acceptability, a comprehensive mix of multiple interventions is necessary for the successful implementation of a PrEP program among this population in Guangxi. [ABSTRACT FROM AUTHOR]

A newfamily of cationic dendron-bearing lipids (CDLs) with poly(amidoamine)dendrons of first to third generation (named as A1, A2, and A3, respectively)was synthesized through a synthesis approach that permits facile variationof chemical structures. All CDLs could effectively bind small interferingRNA (siRNA) to form complexes confirmed by gel retardation analysis.In in vitro transfection experiments, A1/siRNA complexes exhibitedsignificant gene silencing efficiency close to Lipofectamine 2000/siRNAcomplexes and much higher than A2/siRNA and A3/siRNA complexes. Toreveal the underlying reason, we performed a series of experimentalmethods. The results suggested that the CDLs with smaller dendronsizes and higher proportion of hydrophobic segments could bind siRNAto form dendriplex aggregates with more compact structures and highersurface potentials. Therefore, they could be internalized via endocytosismore easily, which was believed to be the main reason for higher genesilencing efficiency. This paper provides an efficient CDL (A1) forsiRNA delivery and indicates great potential for gene therapy. [ABSTRACT FROM AUTHOR]

Highlights: [•] Hypoxia inhibits the medullary respiratory rhythm of rats exposed to smoke in utero. [•] H2S offsets the hypoxia-induced respiratory suppression. [•] H2S alleviates injuries sustained by neurons after utero cigarette smoke exposure. [•] H2S decreases the number of apoptotic neurons and expression of caspase-3 protein. [•] H2S promotes Bcl-2 protein expression and reduces Bax protein and mRNA expression. [Copyright &y& Elsevier]

The nanoscale CRISPR/Cas systems could act as smart enzymatic robots to target the disease-associated cells and nucleic acid signatures and may be potentially added to the armamentarium for efficiently addressing these challenging liver diseases. B CRISPR Nanotheranostics b In article number 2102051, Yeh-Hsing Lao, Qi Zhang, Yu Tao, Mingqiang Li, and co-workers overview the recent advances of CRISPR nanotheranostics in tacking viral hepatitis and hepatocellular carcinoma. [Extracted from the article]