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The cellulose nanocrystals (CNCs) are shown to interact with amine-functionalized polyhedral oligomeric silsesquioxane (POSS-NH

BACKGROUND Apraxia of speech is a disorder of speech-motor planning in which articulation is effortful and error-prone despite normal strength of the articulators. Phonological alexia and agraphia are disorders of reading and writing disproportionately affecting unfamiliar words. These disorders are almost always accompanied by aphasia. OBSERVATIONS A 36-year-old woman underwent resection of a grade IV astrocytoma based in the left middle precentral gyrus, including a cortical site associated with speech arrest during electrocortical stimulation mapping. Following surgery, she exhibited moderate apraxia of speech and difficulty with reading and spelling, both of which improved but persisted 6 months after surgery. A battery of speech and language assessments was administered, revealing preserved comprehension, naming, cognition, and orofacial praxis, with largely isolated deficits in speech-motor planning and the spelling and reading of nonwords. LESSONS This case describes a specific constellation of speech-motor and written language symptoms—apraxia of speech, phonological agraphia, and phonological alexia in the absence of aphasia—which the authors theorize may be attributable to disruption of a single process of “motor-phonological sequencing.” The middle precentral gyrus may play an important role in the planning of motorically complex phonological sequences for production, independent of output modality.

Background Various bacteria and archaea, including halophilic archaeon Halobacterium sp. NRC-1 produce gas vesicle nanoparticles (GVNPs), a unique class of stable, air-filled intracellular proteinaceous nanostructures. GVNPs are an attractive tool for biotechnological applications due to their readily production, purification, and unique physical properties. GVNPs are spindle- or cylinder-shaped, typically with a length of 100 nm to 1.5 μm and a width of 30–250 nm. Multiple monomeric subunits of GvpA and GvpC proteins form the GVNP shell, and several additional proteins are required as minor structural or assembly proteins. The haloarchaeal genetic system has been successfully used to produce and bioengineer GVNPs by fusing several foreign proteins with GvpC and has shown various applications, such as biocatalysis, diagnostics, bioimaging, drug delivery, and vaccine development. Results We demonstrated that native GvpC can be removed in a low salt buffer during the GVNP purification, leaving the GvpA-based GVNP's shell intact and stable under physiological conditions. Here, we report a genetic engineering and chemical modification approach for functionalizing the major GVNP protein, GvpA. This novel approach is based on combinatorial cysteine mutagenesis within GvpA and genetic expansion of the N-terminal and C-terminal regions. Consequently, we generated GvpA single, double, and triple cysteine variant libraries and investigated the impact of mutations on the structure and physical shape of the GVNPs formed. We used a thiol–maleimide chemistry strategy to introduce the biotechnological relevant activity by maleimide-activated streptavidin–biotin and maleimide-activated SpyTag003-SpyCatcher003 mediated functionalization of GVNPs. Conclusion The merger of these genetic and chemical functionalization approaches significantly extends these novel protein nanomaterials' bioengineering and functionalization potential to assemble catalytically active proteins, biomaterials, and vaccines onto one nanoparticle in a modular fashion. Graphical Abstract

Natural speech is full of starts and stops. Here, we studied the neural mechanisms that underlie the inhibitory control of speech, specifically the ability to stop speaking on demand. We recorded direct cortical activity while participants made continuous speech production and were given a visual cue to stop speaking. Neural recordings revealed activity in the premotor frontal cortex associated with speech stopping. Cortical sites showing stop activity were largely distinct from sites involved in active speech production or, more specifically, encoding articulatory movements. Electrocortical stimulation mapping at many premotor sites with stop activity caused involuntary speech arrest, an immediate inability to speak or vocalize. Furthermore, many speech arrest sites did not co-localize with neural activity correlating with speech motor planning or execution, contrary to this long-assumed function in clinical brain mapping. Together, these results suggest a previously unknown premotor cortical network that underlies the inhibitory control of speech, which has significant implications for understanding the dynamics of normal and altered speech production, as well as clinical brain mapping.

Low-dose radioresistance continues to be one of the major limitations for clinical curative treatment of cancer. Luckily, nanotechnology mediated by multifunctional nanomaterials provides potential opportunity to relieve the radioresistance via increasing the radiosensitivity of cancer cells. Herein, an ultrafast fabrication strategy is reported to prepare iron/manganese co-doped bismuth trimetallic nanoparticles (pFMBi NPs) as a multifunctional radiosensitizer for combined therapy. The bismuth matrix provides the intrinsic radiosensitization effect under the low and safe radiation dose via Auger electrons, photoelectrons, and Rayleigh scattering. Meanwhile, co-doping of iron and manganese ions endows pFMBi NPs with both the Fenton reaction property for reactive oxygen species (ROS) generation and photothermal conversion performance for heat production. Additional ROS generation enhances the radiosensitization effect by collaborating with Rayleigh scattering-mediated water radiolysis, and endogenous heat production under near-infrared 808 nm laser irradiation makes DNA more sensitive to radiation and ROS damage. Both in vitro and in vivo evaluations demonstrate the effective antitumor and radiosensitization effects via thermally aided chemodynamic/radiotreatment with a low radiation dose (6 Gy). Therefore, this work provides a potential strategy for overcoming the low-dose radioresistance in cancer therapy.

Organic semiconductor photocatalysts for the production of solar fuels are attractive as they can be synthetically tuned to absorb visible light while simultaneously retaining suitable energy levels to drive a range of processes. However, a greater understanding of the photophysics that determines the function of organic semiconductor heterojunction nanoparticles is needed to optimize performance. Here, we show that such materials can intrinsically generate remarkably long-lived reactive charges, enabling them to efficiently drive sacrificial hydrogen evolution. Our optimized hetereojunction photocatalysts comprise the conjugated polymer PM6 matched with Y6 or PCBM electron acceptors, and achieve external quantum efficiencies of 1.0% to 5.0% at 400 to 900 nm and 8.7% to 2.6% at 400 to 700 nm, respectively. Employing transient and operando spectroscopies, we find that the heterojunction structure in these nanoparticles greatly enhances the generation of long-lived charges (millisecond to second timescale) even in the absence of electron/hole scavengers or Pt. Such long-lived reactive charges open potential applications in water-splitting Z-schemes and in driving kinetically slow and technologically desirable oxidations.

The treatment of huge hepatocellular carcinoma (HCC) is still challengeable due to its deteriorative heterogeneity, for which conventional transarterial chemoembolization (TACE) is proposed as an efficient therapy; however, drug-eluting beads TACE (DEB-TACE) is rarely reported in these patients. Thus, the current study aimed to explore the efficacy, prognostic factors, and safety of DEB-TACE using CalliSpheres in huge HCC patients.Ninety-nine huge HCC patients treated by DEB-TACE using CalliSpheres were retrospectively reviewed. Treatment response, change of tumor markers, liver function indexes, progression-free survival (PFS), and adverse events were retrieved.Objective response rate (ORR) was 66.1%, 48.6%, and 23.8%, then disease control rate (DCR) was 85.5%, 67.6%, and 33.3% at month (M) 1, M3, and M6, respectively; furthermore, carcinoembryonic antigen (CEA) (p = 0.037), alpha fetoprotein (AFP) (p 0.001), and protein induced by vitamin K absence or antagonist-II (PIVKA-II) (p 0.001) were all declined at 1 month after DEB-TACE. The median PFS was 8.3 (95% confidence interval: 6.0-10.6) months with 1-year and 2-year PFS rates of 38.5% and 15.5%, accordingly. Moreover, elevated China liver cancer (CNLC) stage (p = 0.036, hazard ratio (HR): 1.937) and abnormal cancer antigen 199 (p = 0.019, HR: 2.465) were correlated with unfavorable PFS. Besides, liver function indexes were not deteriorated after DEB-TACE. Lastly, main adverse events included pain (20.2%), fever (17.2%), nausea (14.1%), and vomit (9.1%), which were mild and manageable.DEB-TACE using CalliSpheres presents satisfying efficacy and tolerable safety in huge HCC patients, suggesting that it might be a good treatment option for these patients.

Immunotherapy has established a new paradigm for cancer treatment and made many breakthroughs in clinical practice. However, the rarity of immune response suggests that additional intervention is necessary. In recent years, it has been reported that local tumor destruction (LTD) can cause cancer cell death and induce an immunologic response. Thus, the combination of immunotherapy and LTD methods will be a promising approach to improve immune efficiency for cancer treatment. Herein, a nanobiotechnology platform to achieve high-precision LTD for systemic cancer immunotherapy has been successfully constructed. Possessing radio-sensitizing and photothermal properties, the engineered immunoadjuvant-loaded nanoplatform, which could precisely induce radiotherapy (RT)/photothermal therapy (PTT) to eliminate local tumor and meanwhile lead to the release of tumor-derived protein antigens (TDPAs), has been facilely fabricated by commercialized SPG membrane emulsification technology. Further on, the TDPAs could be captured and form personal nanovaccines

Naturally complete mixing promotes the spontaneous redistribution of dissolved oxygen (DO), representing an ideal state for maintaining good water quality, and conducive to the biomineralization of organic matter. Water lifting aerators (WLAs) can extend the periods of complete mixing and increase the initial mixing temperature. To evaluate the influence of artificial-induced continuously mixing on dissolved organic matter (DOM) removal performance, the variations of DOM concentrations, optical characteristic, environmental factors were studied after approaching the total mixing status via WLAs operation. During this process, the dissolved organic carbon reduced by 39.18%, whereas the permanganate index decreased by 20.47%. The optical properties indicate that the DOM became more endogenous and its molecular weight decreased. Based on the results of the Biolog EcoPlates, the microorganisms were maintained at a relatively high metabolic activity in the early stage of induced mixing when the mixing temperature was relatively high, whereas DOM declined at a high rate. With the continuous decrease in the water temperature, both the metabolic capacity and the diversity of aerobic microorganisms significantly decreased, and the rate of organic matter mineralization slowed down. The results of this study demonstrate that the artificial induced mixing largely enhanced the removal DOM performance by providing a long period of aerobic conditions and higher initial temperature.

As nitric oxide (NO) plays significant roles in a variety of physiological processes, the capability for real-time and accurate detection of NO in live organisms is in great demand. Traditional assessments of NO rely on indirect colorimetric techniques or electrochemical sensors that often comprise rigid constituent materials and can hardly satisfy sensitivity and spatial resolution simultaneously. Here, we report a flexible and highly sensitive biosensor based on organic electrochemical transistors (OECTs) capable of continuous and wireless detection of NO in biological systems. By modifying the geometry of the active channel and the gate electrodes of OECTs, devices achieve optimum signal amplification of NO. The sensor exhibits a low response limit, a wide linear range, high sensitivity, and excellent selectivity, with a miniaturized active sensing region compared with a conventional electrochemical sensor. The device demonstrates continuous detection of the nanomolar range of NO in cultured cells for hours without significant signal drift. Real-time and wireless measurement of NO is accomplished for 8 d in the articular cavity of New Zealand White rabbits with anterior cruciate ligament (ACL) rupture injuries. The observed high level of NO is associated with the onset of osteoarthritis (OA) at the later stage. The proposed device platform could provide critical information for the early diagnosis of chronic diseases and timely medical intervention to optimize therapeutic efficacy.

The constant switching frequency space vector pulse width modulation (CSFSVPWM) generates high-frequency harmonics with integer multiples of the switching frequency, making it fail to fully exploit the potential of pulse width modulation (PWM) technique. In this paper, a variable switching frequency space vector pulse width modulation technique with the function of torque ripple prediction is proposed for induction motor drive system, which could optimize the high-frequency harmonic current distribution and torque ripple. The mathematical correlation between inverter average voltage and instantaneous voltage under the space vector pulse width modulation (SVPWM) is first analyzed, followed by the analysis of current ripple in a switching cycle using the typical seven-segment SVPWM, thus the torque ripple of induction motor during this period can be predicted. The switching period is dynamically adjusted according to the magnitude of predicted torque ripple, and the average switching frequency is maintained to be the same with that of CSFSVPWM. The effectiveness of the proposed method in suppressing high-frequency current harmonics and torque ripple is fully verified by experimenting on a 2.2 kW induction motor drive system, and a comprehensive comparison with CSFSVPWM and random PWM modulation is implemented.

The development of high quality magnetic self-healing hydrogels containing well-dispersed magnetic nanoparticle has been a challenging procedure due to unavailable methods of facilely introducing groups that can efficiently stabilize these magnetic nanoparticles in the self-healing hydrogels. In this research, a polymer containing both phenylboronic acid (PBA) and phosphonic acid (PA) groups has been developed by the Kabachnik-Fields (KF) reaction. This polymer well disperses iron oxide nanoparticles (IONPs) through the strong interactions between the PA groups and the surface of the IONPs; thus, this polymer effectively mixed IONPs and poly(vinyl alcohol) (PVA) to form a hydrogel containing well-dispersed IONPs. The resulting hydrogel is self-healing, owing to the dynamic borate ester linkages. Moreover, the presence of the IONPs endowed the hydrogel with magnetic properties, also making it heat-responsive in an alternating magnetic field and expanding its application as a contrast agent for magnetic resonance imaging. The magnetic self-healing hydrogel showed excellent biosafety properties in animal experiments, suggesting its potential as an injectable implant material for biological and medical applications. This research exploits a biocompatible magnetic self-healing hydrogel with well-dispersed IONPs, demonstrating the value of the KF reaction in the development of functional polymers and smart materials, which might prompt a broad study of multicomponent reactions in interdisciplinary fields.

Homologous recombination (HR) is a primary DNA double-strand breaks (DSBs) repair mechanism. The recombinases Rad51 and Dmc1 are highly conserved in the RecA family; Rad51 is mainly responsible for DNA repair in somatic cells during mitosis while Dmc1 only works during meiosis in germ cells. This spatiotemporal difference is probably due to their distinctive mismatch tolerance during HR: Rad51 does not permit HR in the presence of mismatches, whereas Dmc1 can tolerate certain mismatches. Here, the cryo-EM structures of Rad51–DNA and Dmc1–DNA complexes revealed that the major conformational differences between these two proteins are located in their Loop2 regions, which contain invading single-stranded DNA (ssDNA) binding residues and double-stranded DNA (dsDNA) complementary strand binding residues, stabilizing ssDNA and dsDNA in presynaptic and postsynaptic complexes, respectively. By combining molecular dynamic simulation and single-molecule FRET assays, we identified that V273 and D274 in the Loop2 region of human RAD51 (hRAD51), corresponding to P274 and G275 of human DMC1 (hDMC1), are the key residues regulating mismatch tolerance during strand exchange in HR. This HR accuracy control mechanism provides mechanistic insights into the specific roles of Rad51 and Dmc1 in DNA double-strand break repair and may shed light on the regulatory mechanism of genetic recombination in mitosis and meiosis.

Nanoparticles induced potent antitumor immunotherapy plays a significant role for enhancing conventional therapeutic effectiveness. However, revealing the pathway of how nanoagents themselves trigger the host immunity or how to maximize the immunotherapy efficacy still needs further exploration. Herein, rose-like MoS2 nanoflowers modified with 2-deoxy-D-glucose (2-DG) and glucose oxidase (GOx) (MPGGFs) have been successfully fabricated via a one-pot hydrothermal reaction and following one-by-one surface modification as a multifunctional nanocatalyst for photothermal therapy enhanced self-amplified chemodynamic immunotherapy (PTT-co-CDT). By introducing GOx, the obtained MPGGFs exhibited self-amplified chemodynamic therapeutic efficacy under hypoxia tumor microenvironment (TME) because of the raised intracellular H2O2 level via enzyme-catalysis of oxygen. Furthermore, combined with the intrinsic excellent photothermal conversion efficiency of MoS2 nanoflowers, PTT-co-CDT performances by MPGGFs could effectively induce the necroptosis of tumor cells both in vitro and in vivo. Then the induced necroptosis via PTT-co-CDT by MPGGFs could directly trigger host immunity by activating the antigen-specific T-cells (CD4+ and CD8+). Finally, the excellent in vivo safety of MPGGFs makes us believe that the successful construction of rose-like multifunctional nanocatalyst not only has great potentials for self-amplified chemodynamic immunotherapy, but also provides a paradigm for exploring necroptosis triggered host immunity for cancer treatment.

Lung cancer is the leading cause of cancer deaths worldwide and most cancer patients receiving conventional chemotherapy suffer from severe side effects due to the non‐selective effects of chemotherapeutic drugs on normal cells. Targeted nanomaterials can obtain excellent accumulation at the tumor site through their active or passive targeting mechanisms, thereby reducing the toxicity of the drugs in various ways. In this study, hyaluronic acid (HA) which could specifically bind to CD44 on the surface of tumor cells, was used to modify amine‐caged platinum nanoclusters (Pt NCs‐NH2) to obtain targeting HA‐Pt NCs‐NH2. Based on the differential expression of CD44 on the surface of three lung cells (non‐small cell lung cancer cell H1299, small cell lung cancer cell H446, and embryonic lung fibroblast HFL1), HA‐Pt NCs‐NH2 can differentially enter the three cells and achieve their targeting of non‐small cell lung cancer cell (NSCLC) cells. Pt NCs significantly inhibited the proliferation, migration and invasion of NSCLC cells and induced their apoptosis in comparison of classical cisplatin and carboplatin, showing a bright future in early diagnosis and treatment of NSCLC., Hyaluronic acid‐functionalized platinum nanoclusters could differentially enter into three types of cells based on differential CD44 receptor expression. The nanocluster have shown specific targeting and inhibition behaviors on proliferation, invasion, and migration of NSCLC cells.

Immunogenic cell death (ICD) induced by treatment modalities like chemotherapy, radiotherapy, and photothermal and photodynamic therapy has shown great potential to improve the low response rate of various solid tumors in cancer immunotherapy. However, extensive studies have revealed that the efficacy of cancer treatment is limited by the hypoxia and immunosuppression in the tumor microenvironment (TME). To address these challenges, a hypoxia alleviated and one phototriggered thermal/dynamic nanoplatform based on MnO

Background Despite endorsement by medical journals, reporting guidelines have only modestly affected reporting quality. We aimed to identify facilitators and barriers that researchers might encounter when using reporting guidelines. Methods We searched MEDLINE, Embase, PsychINFO, AMED, WHO Global Index Medicus, SciELO, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang Data, VIP Chinese Medical Journal Database, OSF, and MiRoR for research that collected qualitative data to explore researchers’ experiences of using reporting guidelines, published after 1996 in English, Chinese, Spanish, or Portuguese. We appraised studies using CASP-Qual. For thematic synthesis, we applied descriptive codes to all sentences that reported qualitative findings, then aggregated codes inductively into descriptive themes that captured the codes’ meaning. We interpreted and contextualised possible facilitators and barriers from these descriptive themes to create analytic themes. Results From 18 eligible studies, we developed 12 analytic themes. 1) Researchers may not understand guidance as intended. 2) Researchers report many reasons for using reporting guidelines, and that some are more important than others. 3) Researchers use reporting guidelines for different tasks and want guidance to be delivered in ways that fit their needs. 4) Using reporting guidelines has costs which researchers may feel outweigh benefits. 5) Reporting guidelines may need to be revised and updated for different reasons. 6) Researchers report feeling uncertain or worried if they are unable to report all items. 7) Awareness and accessibility may limit reporting guideline usage. 8) Reporting guidelines may be most beneficial to less experienced researchers, but these researchers may find them harder to use. 9) Researchers seek design advice but reporting guidelines may not be the right place to find it. 10) A reporting guideline's scope must be well-balanced and well-defined. 11) Researchers may have to use multiple reporting guidelines, multiplying complexity and costs. 12) Researchers may use checklists but never read the full guidance. Discussion Few reporting guidelines have been evaluated qualitatively. Many studies used surveys which resulted in thin data and were subject to recall bias. Nevertheless, we identified many potential barriers and facilitators. Our findings will help guideline developers and advocates improve reporting guidance dissemination.

Classical models have traditionally focused on the left posterior inferior frontal gyrus (Broca's area) as a key region for motor planning of speech production. However, converging evidence suggests that it is not critical for either speech motor planning or execution. Alternative cortical areas supporting high-level speech motor planning have yet to be defined. In this review, we focus on the precentral gyrus, whose role in speech production is often thought to be limited to lower-level articulatory muscle control. In particular, we highlight neurosurgical investigations that have shed light on a cortical region anatomically located near the midpoint of the precentral gyrus, hence called the middle precentral gyrus (midPrCG). The midPrCG is functionally located between dorsal hand and ventral orofacial cortical representations and exhibits unique sensorimotor and multisensory functions relevant for speech processing. This includes motor control of the larynx, auditory processing, as well as a role in reading and writing. Furthermore, direct electrical stimulation of midPrCG can evoke complex movements, such as vocalization, and selective injury can cause deficits in verbal fluency, such as pure apraxia of speech. Based on these findings, we propose that midPrCG is essential to phonological-motoric aspects of speech production, especially syllabic-level speech sequencing, a role traditionally ascribed to Broca's area. The midPrCG is a cortical brain area that should be included in contemporary models of speech production with a unique role in speech motor planning and execution.

A new nerve guidance conduits (NGCs) named MC@Col containing Type I collagen (Col) and mineralized collagen (MC) was developed, enhancing mechanical and degradation behavior. The physicochemical properties, the mechanical properties and in vitro degradation behavior were all evaluated. The adhesion and proliferation of Schwann cells (SCs) were observed. In the in vivo experiment, MC@Col NGC and other conduits including Col, chitosan (CST) and polycaprolactone (PCL) conduit were implanted to repair a 10-mm-long Sprague-Dawley rat’s sciatic nerve defect. Histological analyses, morphological analyses, electrophysiological analyses and further gait analyses were all evaluated after implantation in 12 weeks. The strength and degradation performance of the MC@Col NGC were improved by the addition of MC in comparison with pure Col NGC. In vitro cytocompatibility evaluation revealed that the SCs had good viability, attachment and proliferation in the MC@Col. In in vivo results, the regenerative outcomes of MC@Col NGC were close to those by an autologous nerve graft in some respects, but superior to those by Col, CST and PCL conduits. The MC@Col NGC exhibited good mechanical performance as well as biocompatibility to bridge nerve gap and guide nerve regeneration, thus showing great promising potential as a new type of conduit in clinical applications.

This study aimed to analyze the transcriptome of C. rupestris under Pb2+ stress by using high-throughput sequencing technology, observe the changes of gene expression and metabolic pathway after three and five days under 1.0 and 5.0 mg/L of Pb2+ treatment, and analyze the differentially expressed genes (DEGs) and related functional genes after Pb2+ treatment. Metabolic pathways were revealed through Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Results show that DEGs increased significantly with the increase of Pb2+ concentration and stress time. A total of 32 genes were closely related to Pb2+ stress response. GO analysis identified two major transporter proteins, namely, ATP-binding transport protein-related (ABC transporters) and zinc finger CCHC domain containing protein (Zfp) in C. rupestris. Pthr19248, pthr19211, Zfp pthr23002, Zfp p48znf pthr12681, Zfp 294 pthr12389, and Zfp pthr23067 played important roles against Pb2+ toxicity and its absorption in C. rupestris. KEGG pathway analysis suggested that ABCA1, ATM, and ABCD3 were closely related to Pb2+ absorption. Pb2+ stress was mainly involved in metallothionein (MT), plant hormone signal transduction, ABC transporters, and glutathione (GSH) metabolism.

This study aimed to analyze the transcriptome of

The coordination between neurogenesis and angiogenesis plays an important role in nerve tissue development and regeneration. Recently, using bioactive materials to drive neurogenic and angiogenic responses has gained increasing attention. Understanding the neurovascular link between regulatory cues offers valuable insight into the mechanisms underlying nerve regeneration and the design of new bioactive materials. In this study, we utilized a dual-functionalized peptide nanofiber hydrogel presenting the brain-derived neurotrophic factor and vascular endothelial growth factor mimetic peptides RGIDKRHWNSQ (RGI) and KLTWQELYQLKYKGI (KLT) to construct an artificial neurovascular microenvironment. The dual-functionalized peptide nanofiber hydrogel enhanced the neurite outgrowth of pheochromocytoma (PC12) cells and tube-like structures formation of human umbilical vein endothelial cells (HUVECs) in vitro, and promoted rapid lesion infiltration of neural and vascular cells in a rat brain injury model. Using indirect co-culture models, we found that the dual-functionalized peptide hydrogel effectively mediated neurovascular crosstalk by regulating secretion of paracrine factors from PC12 cells and HUVECs. When the two cells types were directly co-cultured on the dual-functionalized peptide hydrogel, the efficiency of cell-cell communication was enhanced, which further accelerated the differentiation and maturation of PC12 cells with an increased number of pseudopodia and spread morphology, and HUVECs tube-like structure formation. In summary, the dual-functionalized peptide nanofiber hydrogel successfully formed an artificial neurovascular niche to directly regulate the behaviors of neural and vascular cells and promote their neurovascular crosstalk through paracrine signaling and direct cell-cell contact.

For the purpose of improving the quality of life and minimizing the psychological morbidity of a mastectomy, breast-conserving treatment (BCT) has become the more preferable choice in breast cancer patients. Meanwhile, tumor hypoxia has been increasingly recognized as a major deleterious factor in cancer therapies. In the current study, a novel, effective, and noninvasive magnetothermodynamic strategy based on an oxygen-independent free-radical burst for hypoxia-overcoming BCT is proposed. Radical precursor (AIPH) and iron oxide nanoparticles (IONPs) are coincorporated within the alginate (ALG) hydrogel, which is formed in situ within the tumor tissue by leveraging the cross-linking effect induced by the local physiological Ca2+ with ALG solution. Inductive heating is mediated by IONPs under AMF exposure, and consequently, regardless of the tumor hypoxia condition, a local free-radical burst is achieved by thermal decomposition of AIPH via AMF responsivity. The combination of magnetic hyperthermia and oxygen-irrelevant free-radical production effectively enhances the in vitro cytotoxic effect and also remarkably inhibits tumor proliferation. This study provides a valuable protocol for an hypoxia-overcoming strategy and also an alternative formulation candidate for noninvasive BCT.

Introduction Melasma is a chronic and recurrent skin problem for which an effective therapy is currently lacking. Platelet-rich plasma (PRP) has recently emerged as a novel treatment for melasma, but to date there has been no systematic evaluation of its efficacy and safety. Methods The Web of Science, PubMed, EMBASE, China National Knowledge Infrastructure (CNKI) and the Cochrane Library databases were searched for relevant articles using the search items “melasma,” “chloasma” and “platelet‐rich plasma.” STATA version 15.1 software was used to analyze data. Study outcomes were calculated using standardized mean differences with 95% confidence intervals (CIs). Results The database search identified ten studies involving 395 adult patients that met the inclusion criteria and were included in the meta-analysis. Analysis of pre- and post-treatment data from these studies revealed that the post-treatment modified Melasma Area and Severity Index (mMASI) score decreased by 1.18 (95% CI 0.89–1.47; p = 0.02). Subjective satisfaction evaluation of PRP treatment showed that melasma treated with the combination therapy of PRP + microneedling may have been the most efficacious treatment compared to PRP alone or in combination with intradermal injection. Adverse reactions were minor, with only a few patients reporting local congestion, temporary erythema, hyperpigmentation and discoloration. Conclusion These results support the efficacy and safety of PRP used in combination or alone as treatment for melasma. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-021-00575-z.

Background Reporting quality is a critical issue in health sciences. Adopting the reporting guidelines has been approved to be an effective way of enhancing the reporting quality and transparency of clinical research. In 2012, we found that only 7 (7/1221, 0.6%) journals adopted the Consolidated Standards of Reporting Trials (CONSORT) statement in China. The aim of the study was to know the implementation status of CONSORT and other reporting guidelines about clinical studies in China. Methods A cross-sectional bibliometric study was conducted. Eight medical databases were systematically searched, and 1039 medical journals published in mainland China, Hong Kong, Macau, and Taiwan were included. The basic characteristics, including subject, language, publication place, journal-indexed databases, and journal impact factors were extracted. The endorsement of reporting guidelines was assessed by a modified 5-level evaluation tool, namely i) positive active, ii) positive weak, iii) passive moderate, iv) passive weak and v) none. Results Among included journals, 24.1% endorsed CONSORT, and 0.8% endorsed CONSORT extensions. For STROBE (STrengthening the Reporting of Observational Studies in Epidemiology), PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), STARD (An Updated List of Essential Items for Reporting Diagnostic Accuracy Studies), CARE (CAse REport guidelines), the endorsement proportion were 17.2, 16.6, 16.4, and 14.8% respectively. The endorsement proportion for SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials), TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis), AGREE (Appraisal of Guidelines, Research, and Evaluation), and RIGHT (Reporting Items for Practice Guidelines in Healthcare) were below 0.7%. Conclusions Our results showed that the implementation of reporting guidelines was low. We suggest the following initiatives including i) enhancing the level of journal endorsement for reporting guidelines; ii) strengthening the collaboration among authors, reviewers, editors, and other stakeholders; iii) providing training courses for stakeholders; iv) establishing bases for reporting guidelines network in China; v) adopting the endorsement of reporting guidelines in the policies of the China Periodicals Association (CPA); vi) promoting Chinese medical journals into the international evaluation system and publish in English.

Many cryogenic electron microscopy (cryo-EM) single particle analyses are constrained by the sample preparation step upon which aggregation, dissociation, and/or preferential orientation of particles can be introduced. Here, we report how we solved these problems in the case of CDC48A, a hexameric AAA ATPase from Arabidopsis thaliana. CDC48A hexamers are well preserved under negative staining conditions but disassemble during grid freezing using the classical blotting method. Vitrification of grids using the blot-free Chameleon method preserved the integrity of particles but resulted in their strong preferential orientation. We then used a strategy where we improved in parallel the purification of CDC48A and the conditions for cryo-EM data acquisition. Indeed, we noted that images taken from thicker ice presented an even distribution of intact particles with random orientations, but resulted in a lower image resolution. Consequently, in our case, distribution, orientation, image resolution, and the integrity of particles were tightly correlated with ice thickness. By combining the more homogeneous and stable CDC48A hexamers resulting from our improved purification protocol with an iterative search across different ice thicknesses, we identified an intermediate thickness that retained sufficiently high-resolution structural information while maintaining a complete distribution of particle orientations. Our approach may provide a simple, fast, and generally applicable strategy to record data of sufficient quality under standard laboratory and microscope settings. This method may be of particular value when time and resources are limited., Frontiers in Molecular Biosciences, 9, ISSN:2296-889X

Although hypolimnetic anoxia is a common occurrence in deep lakes and reservoirs, understanding the processes of oxygen depletion in water columns and sediment is challenging. This study investigates oxygen depletion in both the hypolimnion and sediments in a stratified reservoir. The areal hypolimnetic oxygen demand (AHOD) and sediment oxygen demand (SOD) were evaluated to determine key factors of hypolimnetic anoxia. To evaluate the characteristics of the AHOD in the Jinpen Reservoir (JPR), China, 4 years of field observations of dissolved oxygen (DO) and temperature datasets in the water column are analyzed. SOD was calculated as the sum of the sediment oxygen uptake ( $${\text{J}}_{{\text{O}}_{2}}$$ ) and the flux of reduced substances from deeper sediment layers into the overlying water (Fred), where $${\text{J}}_{{\text{O}}_{2}}$$ was obtained from DO profiles across the sediment–water interface (SWI) at a depth of approximately 94 m in the reservoir, and Fred was obtained from sediment cores. The AHOD in the JPR varied from 0.299 to 1.451 g m−2 day−1 during the summer stratification between 2014 and 2017. The SOD, containing $${\text{J}}_{{\text{O}}_{2}}$$ and Fred, decreased from 0.534 to 0.386 g m−2 day−1 during stratification. Within the SOD, $${\text{J}}_{{\text{O}}_{2}}$$ decreased from 0.415 to 0.168 g m−2 day−1, whereas Fred increased from 0.119 to 0.218 g m−2 day−1. The increase in primary productivity (e.g., diatom blooms), inflows during rainfall, and oxygen concentrations can significantly increase AHOD. The relative importance of $${\text{J}}_{{\text{O}}_{2}}$$ at 40–70% of the SOD is high in the JPR; thus, oxic respiration of organic carbon is the dominant pathway of DO consumption.

With the rapid development of artificial intelligence and the increasing demand for legal intelligence, using AI methods to predict legal judgments has become a hot spot in recent years. Charge prediction is one of the core tasks of Legal Judgment Prediction (LJP). It aims to predict charge from complicated legal facts, so as to help the court make judgments or provide legal professional guidance to non-professionals. In the field of legalAI, interpretability is crucial compared to others. Reasonable interpretability can eliminate hidden dangers such as gender discrimination and provide support for judges’ decisions. However, how to add the legal theory framework to the modeling to improve the interpretability is a challenge, which has few researches at present. To address this problem, we use Double-layer Criminal System as a guide to build Charge Prediction modeling called DCSCP which aims to predict charges in the criminal law of China. In general, our characteristic is to achieve multi-granularity inference of legal charges by obtaining the subjective and objective elements from the fact descriptions of legal cases. Specifically, our approach is performed in two steps: (1) extract the objective elements from the fact description and use them to generate candidate charges to achieve coarse-grained prediction; (2) extract the subjective elements from the fact description, and design the first-order predicate logic inference to realize the fine-grained charge inference in combination with the candidate charges. Experimental results show that our DCSCP can provide interpretable predictions, and it can maintain performance compared to other state-of-the-art charge prediction models.

Nowadays, controllable drug release is a vitally important strategy for cancer treatment and usually realized using implanting biocompatible devices. However, these devices need to be removed by another surgery after the function fails, which brings the risks of inflammation or potential death. In this article, a biodegradable flexible electronic device with controllable drug (paclitaxel) release was proposed for cancer treatment. The device is powered by an external alternating magnetic field to generate internal resistance heat and promote drug release loaded on the substrate. Moreover, the device temperature can even reach to 65 °C, which was sufficient for controllable drug release. This device also has similar mechanical properties to human tissues and can autonomously degrade due to the structure design of the circuit and degradable compositions. Finally, it is confirmed that the device has a good inhibitory effect on the proliferation of breast cancer cells (MCF-7) and could be completely degraded in vitro. Thus, its great biodegradability and conformity can relieve patients of second operation, and the device proposed in this paper provides a promising solution to complete conquest of cancer in situ.

In recent years, metal-phenolic networks (MPNs) have attracted increasing attention for the engineering of multi-functional platforms because of their easy fabrication processes, excellent physicochemical properties, outstanding biocompatibility, and promising theranostic applications. In this review, we summarize recent progress in the design, synthesis, shape-control, biocompatibility evaluation, and potential theranostic applications of MPNs, especially for cancer theranostics. First, we provide an overview of various MPN systems, relevant self-assembly procedures, and shape-controllable preparation. The in vitro and in vivo biocompatibility evaluation of MPNs is also discussed, including co-incubation viability, adhesion, bio-distribution, and inflammation. Finally, we highlight the significant achievements of various MPNs for cancer theranostics, such as tumor imaging, drug delivery, photothermal therapy, radiotherapy, and chemo- and photo-dynamic therapy. This review provides a comprehensive background on the design and controllable synthesis, in vitro and in vivo biocompatibility evaluation, applications of MPNs as cancer theranostic agents, and presents an overview of the most up-to-date achievements in this field.

The selection of proppant particle size significantly impacts the gas output and gas production period of the extracting coalbed methane (CBM). This study combines theoretical analysis and permeability testing, based on the in situ stress distribution characteristics of the coal seam in Wangjiazhai Coal Mine, Guizhou Province, conducted on artificial fractures with different particle size proppant combinations during the cyclic loading and unloading. The findings indicate that the coal sample with two particle sizes of proppant has more permeability and smaller stress sensitivity coefficient than the coal sample with a single particle size proppant; as effective stress increases, the coal sample with the maximum permeability and the smallest stress sensitivity coefficient is placed with a proppant ratio of 20/40 mesh to 40/70 mesh of 1–3. The stress sensitivity coefficient and the permeability decrease with an increase in the number of confining pressure cycles. The increase in the proppant embedding depth has a hysteresis phenomenon with the increase in the effective stress, and the coal sample with a proppant ratio of 20/40 mesh to 40/70 mesh of 1–3 has the smallest embedded depth. The proppant will cause damage to the fracture surface of the coal seam. This study provides technical support for efficiently extracting the CBM resources that are difficult to exploit in Guizhou Province.

In the current study, a novel intrinsic functionalization approach based on composite feeding additive for silkworms to produce silk fibers (SFs) with enhanced mechanical properties has been succes...

Due to the relatively low photo-thermal conversion efficiency and poor tumor targeting capacity, phototheranostic nanoagents encounter some challenges in cancer photothermal therapy. To address this problem, in the current research we developed vacancy-rich MoSe2-x (0 ≤ x ≤ 1) nanoflowers (MNFs) with molecular 2-deoxy-D-glucose (2-DG) as the activity target, which could be used as a novel phototheranostic nanoagent in the photoacoustic imaging guided chemo-photothermal synergistic therapy. This selenium-deficient structure endows MNFs with high photothermal conversion efficiency (41.7%) due to the strong localized surface plasmon resonances. Besides, the surface linked 2-DG molecules and the flower-like morphology in the nanoagents promoted the targeting effect (active and passive), thus facilitating the efficient concentration of the nanoagents within the tumor site. Both in vitro and in vivo anti-tumor experiments have demonstrated the high synergistic efficacy promoted by MNFs and complete tumor eradication with lower administration dosages could be achieved. This rational design of nanoparticles not only provided the paradigm of high therapeutic efficacy of a chemo-photothermal protocol for precise cancer theranostics, but also expanded the scope of nanomedical applications using semiconductor-based nanoplatforms through well-defined designing of their microstructures and physiochemical properties.

Developing simple and efficient nanotheranostic platforms with behavior responsive to the acid microenvironment of a tumor is of great significance for accurate tumor diagnosis and therapy. In this study, a smart 2D nanotheranostic platform has been successfully fabricated by doping functional ferrous ions into as-synthesized MgAl-layered double hydroxide (LDH) with doxurubicin (DOX) loading to form Fe-LDH/DOX NPs, which achieved magnetic resonance imaging (MRI)-guided synergistic chemo/photothermal therapy for breast cancer. The doping of ferrous ions into Fe-LDH/DOX enabled a strong photo-induced heating ability with a high photothermal conversion efficiency of 45.67%, which could be combined with the antitumor drug DOX to achieve the synergistic effect of photothermal therapy (PTT) and chemotherapy for killing tumor cells. Additionally, its in vitro pH-dependent degradation behavior and T2-weighted MRI effect revealed that the as-prepared Fe-LDH/DOX is sensitive to the tumor acid microenvironment. Most importantly, the growth rate of tumors in 4T1 bearing mice could be effectively inhibited after the synergistic treatment of PTT and chemotherapy by Fe-LDH/DOX. These results show that doping functional metal ions into LDH NPs may open a novel approach to fabricating an LDH NP-based nanotheranostics platform with advanced diagnostic and therapeutic performances.