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Organic electrochemical transistors (OECTs) possess low operating voltage and excellent amplification capability and show promising applications in biosensors and flexible electronics. However, the active layers of OECTs are usually dense films, which show limited ion penetration/transport, resulting in limited performances of OECTs. Here, unprecedented high‐performance flexible multifunctional OECTs based on nanoporous (mainly 2–60 nm), high‐specific‐surface‐area (255–281 m2 g−1), and flexible conjugated polymer aerogel films are developed. The nanoporous structures effectively facilitate ion penetration/transport, leading to significantly enhanced transconductance (48.5–53.5 mS) and on/off ratio (6.4 × 104) of the OECTs compared with those of dense devices. The resulting OECT‐based glucose sensors exhibit an ultralow detection limit of 1 pm, approximately two to three orders of magnitude lower than those of the previously reported OECT glucose sensors, and an ultrabroad detection range of 1 pm–5 m. They can detect trace amounts of glucose in sweat, serum, saliva, and urine in real time. Moreover, the OECTs can be used for high‐performance flexible artificial synapses and electrocardiogram monitoring. This work provides a powerful strategy toward highly sensitive biosensors, artificial synapses, and electrophysiological signal monitoring. [ABSTRACT FROM AUTHOR]

With the increasing demands for artificial intelligence, robotics, electronic skin, healthcare, and energy storage/conversion, the research focus on flexible electronics has started to shift from being merely bendable and rollable to being stretchable. In recent years, stretchable aerogels and foams have drawn significant attention in the field of flexible electronics due to their unique porous structures, low density, high porosity, and high flexibility. This work provides a comprehensive review of the state‐of‐the‐art developments in stretchable aerogels and foams, encompassing their preparation, structures, properties, and applications. The preparation methods, typical structures of stretchable aerogels and foams, stretching principle, and the relationship between their structures, stretchability, and other properties are investigated. Their latest applications in stretchable strain/pressure sensors, electrodes and conductors, chemical sensors and biosensors, supercapacitors, batteries, triboelectric nanogenerators, electromagnetic shielding, microwave absorption, thermal management, adsorption, separation/filtration, and shape memory are introduced. Furthermore, the challenges and opportunities of stretchable aerogels and foams are summarized. This work provides a guideline for the development of stretchable aerogels and foams and next‐generation high‐performance flexible electronics based on stretchable porous materials. [ABSTRACT FROM AUTHOR]

Enhancing the efficiency of charge carrier separation is crucial for improving the performance of photocatalysts, thereby offering more effective solutions to energy and environmental pollution challenges. In this study, a carbon‐deficient ultra‐thin porous g‐C3N4 (Vc‐UPCN) was synthesized and subsequently was integrated with Bi2Fe4O9 (BFO) using a sonochemical self‐assembly technique, a Bi2Fe4O9/Vc‐UPCN (BC) photocatalyst featuring a Z‐scheme heterojunction. The BC catalyst was subjected to corona poling treatment to obtain BCp, which possesses an intrinsic electric field. Compared with pure BFO and Vc‐UPCN, the BC heterojunction exhibited higher photo‐generated electron–hole separation efficiency and photodegradation ability. Upon introduction of corona polarization, the photocatalytic performance of BC was further enhanced. Specifically, BCp‐15 (BFO/BC mass fraction = 15) achieved complete degradation of methylene blue (MB) within 30 min. BCp‐15 demonstrated that its degradation efficiency for MB was 1.28 times higher than that of BC‐15, 1.85 times higher than that of Vc‐UPCN, and impressive 7.69 times higher than that of pure BFO. The coupling effect of the heterojunction and ferroelectric polarization significantly improved the separation efficiency of photo‐generated carriers in BCp. This study is expected to provide a reference for the synergistic application of heterojunction and ferroelectric polarization in traditional semiconductor photocatalysis. [ABSTRACT FROM AUTHOR]

Highly stretchable aerogel films are attractive for advanced next‐generation stretchable electronics. However, it is a great challenge to achieve high stretchability for aerogel films. Here, several types of unprecedented ultra‐stretchable semiconducting polymer‐based aerogel films with crimpled porous structures are developed via crosslinking and template methods combined with uniaxial and biaxial pre‐stretching strategies. The semiconducting aerogel films obtained by uniaxial pre‐stretching exhibit ultrahigh stretchability up to 100–200%, while those obtained by biaxial pre‐stretching show high biaxial stretchability up to 50%. The resulting aerogel films show strain‐insensitive electrical and joule heating properties. A prototype of the aerogel film‐based stretchable organic electrochemical transistor (OECT) is developed for the first time. Benefiting from their unique porous structures, the aerogel film‐based OECTs exhibit enhanced on/off ratio and transconductance compared with corresponding dense film‐based OECTs, high stretchability up to 100%, and high stretching stability with 10 000 stretching cycles under 30% strain. It is demonstrated that the aerogel film‐based OECTs can be applied as high‐performance stretchable artificial synapses and biosensors. This work gives a versatile strategy toward highly stretchable aerogel films promising for flexible electronics. [ABSTRACT FROM AUTHOR]

CsPbBr3 nanoplates (NPs) have shown great potential in diverse optoelectronic applications. Despite the wonderful luminescence properties, the inherent instability of these NPs hinders their use in practical situations. Herein, a facile water‐assisted strategy is reported to synthesize highly stable blue emission CsPbBr3 NPs encapsulated in PbBr(OH). The introduction of water directly into the reaction mixture is pivotal, as it triggers the transformation of bulk CsPbBr3 nanocubes into 2‐D CsPbBr3 NPs within the PbBr(OH) matrix, resulting in the formation of CsPbBr3@PbBr(OH) microbricks. Remarkably, the water content in the reaction mixture allows the control of the number of perovskite layers in the NPs, thus enabling the emission color to be tuned from deep blue to green. The unconventional approach presented herein not only offers a cost‐effective pathway to synthesize blue‐emitting perovskites which are highly stable in a wide variety of polar and non‐polar solvents, but also holds immense potential for propelling the advancement of high‐performance LEDs and other optoelectronic devices. The findings underscore the significance of water in dictating the growth dynamics and emission characteristics of perovskite NPs, paving the way for their practical application. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) infection is a crucial public health issue and a major cause of liver disease, such as cirrhosis and hepatocellular carcinoma. At present, orally administered small molecule drugs, such as nucleoside / nucleotide analogues, are recommended as the first‐line treatment for HBV. However, the therapeutic efficacy of these drugs is hindered by off‐target toxicity caused by the whole‐body permeation distribution of these oral drugs. As an emerging drug delivery technology, systemically administered nanocarriers can enhance the aqueous solubility and stability of encapsulated drugs, prolong circulation times, and deliver them efficiently to the liver, showing great promise for increasing the safety and efficacy of small molecule drugs. Furthermore, nanocarriers also accelerate the clinical translation of new therapies, such as nucleic acids and vaccines. This review article highlights the progress of nanoparticle delivery systems in anti‐HBV therapeutics and discusses the opportunities and challenges for the future development of anti‐HBV nanotherapeutics. [ABSTRACT FROM AUTHOR]

This review is aiming to systematically elucidate the unique role of nanotechnology in optimizing therapeutic modalities for combinatorial cancer immunotherapy, which enables the synergistic integration of multiple treatment strategies. In particular, nanotechnology has enabled the synergistic combination of immunotherapy with physical therapies, chemotherapy, metal therapy, and nucleic acid therapy. In each combination regimen, nanocarriers play multifaceted roles by achieving targeted codelivery of different therapeutics and optimizing each individual treatment modality. This offers new paradigms to guide precision medicine in cancer treatment. Immunotherapy alone is unlikely to achieve personalized precision medicine for cancer, and new treatment modalities are needed in the future. To overcome technical bottlenecks and realize precise regulation of the tumor microenvironment for personalized cancer treatment, it is crucial to develop novel nanosystems with integrated sensing, targeting, and therapeutic functionalities. [ABSTRACT FROM AUTHOR]

MXene‐based aerogels are promising candidates for wearable electronics due to their unique structures and properties. However, the reported MXene‐based aerogels show poor stretchability, significantly restricting their applications in wearable electronics. Herein, unprecedented highly stretchable MXene‐based aerogels with crimpled and reentrant microstructures are developed via synergistic assembly of MXene and flexible polymers combined with uniaxial and biaxial hot‐pressing strategies. The uniaxially hot‐pressed MXene‐based meta‐aerogels show compressed and crimpled microstructures and combine ultrahigh stretchability up to 427%, high elasticity, high compressibility, high fatigue resistance upon compression and stretching, and near‐zero Poisson's ratios. The biaxially hot‐pressed MXene‐based meta‐aerogels exhibit reentrant microstructures and achieve high stretchability and negative Poisson's ratios upon stretching in different directions, which have never been realized by traditional aerogels. It is demonstrated that they can be used for ultrabroad‐range pressure/strain sensors, highly stretchable triboelectric nanogenerators, and smart thermal management with tunable thermal insulation and Joule heating performances achieved by stretching. This work opens a new way to highly stretchable aerogels with near‐zero and negative Poisson's ratios promising in wearable electronics, nanogenerators, thermal management, energy storage, etc. [ABSTRACT FROM AUTHOR]

Traditional Chinese medicine (TCM) is widely used in clinical practice, including skin and gastrointestinal diseases. Here, a potential TCM QY305 (T‐QY305) is reported that can modulate the recruitment of neutrophil in skin and colon tissue thus reducing cutaneous adverse reaction and diarrhea induced by epidermal growth factor receptor inhibitors (EGFRIs). On another hand, the T‐QY305 formula, through regulating neutrophil recruitment features would highlight the presence of N‐QY305, a subunit nanostructure contained in T‐QY305, and confirm its role as potentially being the biomaterial conferring to T‐QY305 its pharmacodynamic features. Here, the clinical records of two patients are analyzed expressing cutaneous adverse reaction and demonstrate positive effect of T‐QY305 on the simultaneous inhibition of both cutaneous adverse reaction and diarrhea in animal models. The satisfying results obtained from T‐QY305, lead to further process to the isolation of N‐QY305 from T‐QY305, in order to demonstrate that the potency of T‐QY305 originates from the nanostructure N‐QY305. Compared to T‐QY305, N‐QY305 exhibits higher potency upon reducing adverse reactions. The data represent a promising candidate for reducing cutaneous adverse reaction and diarrhea, meanwhile proposing a new strategy to highlight the presence of nanostructures being the "King" of Chinese medicine formula as the pharmacodynamic basis. [ABSTRACT FROM AUTHOR]

Photoacoustic (PA) imaging is emerging as one of the important non‐invasive imaging techniques in biomedical research. Small molecule‐ second near‐infrared window (NIR‐II) PA dyes combined with imaging data can provide comprehensive and in‐depth in vivo physiological and pathological information. However, the NIR‐II PA dyes usually exhibit "always‐on" properties due to the lack of a readily optically tunable group, which hinders the further applications in vivo. Herein, a novel class of dyes GX have been designed and synthesized as an activatable NIR‐II PA platform, in which the absorption/emission wavelength of GX‐5 extends up to 1082/1360 nm. Importantly, the GX dyes have a strong tissue penetration depth and high‐resolution for the mouse vasculature structures in NIR‐II PA 3D imaging and high signal‐to‐noise ratio in NIR‐II fluorescence (FL) imaging. Furthermore, to demonstrate the applicability of GX dyes, the first NIR‐II PA probe GX‐5‐CO activated by carbon monoxide (CO) was engineered and employed to reveal the enhancement of the CO levels in the hypertensive mice by high‐contrast NIR‐II PA and FL imaging. We expect that many derivatives of GX dyes will be developed to afford versatile NIR‐II PA platforms for designing a wide variety activatable NIR‐II PA probes as biomedical tools. [ABSTRACT FROM AUTHOR]

Brain health is the humans' primary goal in achieving health and longevity. Brainstem glioma (BSG) has a high disability and mortality rate, posing a serious threat to children's brain health. Delivery of drugs to the brainstem is limited by poor tumor targeting and low blood‐brain barrier (BBB) permeability. Thus, it is a great challenge to construct intracranial drug delivery systems with strong biocompatibility, low immunogenicity, and high BBB permeability for the delivery of drugs targeting BSG. Exosomes, as the next generation of novel delivery systems, have been widely used to across the BBB due to their advantages of good biocompatibility, stability, and permeability of the BBB and have made corresponding breakthroughs in targeted drug delivery for CNS diseases. This review summarizes natural, polypeptide functionalized, and physical methods‐assisted brain‐targeted exosomes‐based drug delivery systems, the drug treatment bottleneck of BSG, and highlights the potential of using a brain‐targeted exosomes‐based drug delivery system to overcome the drug treatment bottleneck of BSG. It provides new insights into using exosomes‐based drug delivery for BSG treatment. [ABSTRACT FROM AUTHOR]

Patients with triple‐negative breast cancer (TNBC) have the worst clinical outcomes when compared to other subtypes of breast cancer. Nanotechnology‐assisted photothermal therapy (PTT) opens new opportunities for precise cancer treatment. However, thermoresistance caused by PTT, as well as uncertainty in the physiological metabolism of existing phototherapeutic nanoformulations, severely limit their clinical applications. Herein, based on the clinically chemotherapeutic drug mitoxantrone (MTO), a multifunctional nanoplatform (MTO‐micelles) is developed to realize mutually synergistic mild‐photothermal chemotherapy. MTO with excellent near‐infrared absorption (≈669 nm) can function not only as a chemotherapeutic agent but also as a photothermal transduction agent with elevated photothermal conversion efficacy (ƞ = 54.62%). MTO‐micelles can accumulate at the tumor site through the enhanced permeability and retention effect. Following local near‐infrared irradiation, mild hyperthermia (<50 °C) assists MTO in binding tumor cell DNA, resulting in chemotherapeutic sensitization. In addition, downregulation of heat shock protein 70 (HSP70) expression due to enhanced DNA damage can in turn weaken tumor thermoresistance, boosting the efficacy of mild PTT. Both in vitro and in vivo studies indicate that MTO‐micelles possess excellent synergetic tumor inhibition effects. Therefore, the mild‐photothermal chemotherapy strategy based on MTO‐micelles has a promising prospect in the clinical transformation of TNBC treatment. [ABSTRACT FROM AUTHOR]

Leukemia inhibitory factor (LIF) is an important growth factor that supports the culture and maintenance of spermatogonial stem cells (SSCs) by suppressing spontaneous differentiation. Different LIF sequences may lead to differences in function. The protein sequences of buffalo LIF and mouse LIF differed by 65.5% according to MEGA software analysis. The PB‐LIF‐GFP‐Puro vector was constructed, and the CHO‐K1 cell line was established. The final LIF protein concentration in the CHO‐K1 cell culture medium was approximately 4.268 ng/mL. Here, we report that buffalo LIF effectively maintains the self‐renewal of buffalo spermatogonia during culture. Buffalo spermatogonia were cultured in conditioned medium containing no LIF (0 ng/mL), mouse LIF (1 ng/mL), mouse LIF (10 ng/mL), or buffalo LIF (1 ng/mL). Furthermore, the effects of mouse LIF and buffalo LIF culture on the maintenance of buffalo spermatogonia were determined by analyzing cell colony formation, quantitative real‐time polymerase chain reaction, cell immunofluorescence, and cell counting. The buffalo LIF (1 ng/mL) group showed similar maintenance of the proliferation of buffalo spermatogonia to that in the mouse LIF (10 ng/mL) group. These results demonstrated that the proliferation of buffalo spermatogonia can be maintained in vitro by adding a low dose of buffalo LIF. This study provides a foundation for the further optimization of in vitro buffalo SSC culture systems. [ABSTRACT FROM AUTHOR]

The Zn content in cereal seeds is an important trait for crop production as well as for human health. However, little is known about how Zn is loaded to plant seeds. Here, through a genome‐wide association study (GWAS), we identify the Zn‐NA (nicotianamine) transporter gene ZmYSL2 that is responsible for loading Zn to maize kernels. High promoter sequence variation in ZmYSL2 most likely drives the natural variation in Zn concentrations in maize kernels. ZmYSL2 is specifically localized on the plasma membrane facing the maternal tissue of the basal endosperm transfer cell layer (BETL) and functions in loading Zn‐NA into the BETL. Overexpression of ZmYSL2 increases the Zn concentration in the kernels by 31.6%, which achieves the goal of Zn biofortification of maize. These findings resolve the mystery underlying the loading of Zn into plant seeds, providing an efficient strategy for breeding or engineering maize varieties with enriched Zn nutrition. Synopsis: The metal‐NA (Nicotianamine) transporter ZmYSL2 loads Zn from the maternal tissue into maize kernels. Overexpression of ZmYSL2 increases the amount of Zn in maize kernels, providing a potential approach for breeding Zn‐rich crop. Polymorphisms in basal endosperm transfer cell layer (BETL) localized ZmYSL2 correlate with natural variations in the Zn concentration of maize kernels.The opaque phenotype of ZmYSL2 mutants is due to deficiency of Zn rather than Fe in the kernels.Overexpression of ZmYSL2 increases the Zn concentration in the kernels by 31.6%, which achieves the goal of Zn biofortification of maize. [ABSTRACT FROM AUTHOR]

Broad‐range‐response pressure‐sensitive wearable electronics are urgently needed but their preparation remains a challenge. Herein, we report unprecedented bioinspired wearable electronics based on stretchable and superelastic reduced graphene oxide/polyurethane nanocomposite aerogels with gradient porous structures by a sol‐gel/hot pressing/freeze casting/ambient pressure drying strategy. The gradient structure with a hot‐pressed layer promotes strain transfer and resistance variation under high pressures, leading to an ultrabroad detection range of 1 Pa–12.6 MPa, one of the broadest ranges ever reported. They can withstand 10 000 compression cycles under 1 MPa, which can't be achieved by traditional flexible pressure sensors. They can be applied for broad‐range‐response electronic skins and monitoring various physical signals/motions and ultrahigh pressures of automobile tires. Moreover, the gradient aerogels can be used as high‐efficient gradient separators for water purification. [ABSTRACT FROM AUTHOR]

Well shut-in and drainage after shale gas fracturing are important factors affecting the productivity. Due to the imperfect optimization method of shale gas flowback, there has been no clear explanation for the problems such as "formulation of reasonable well shut-in time" and "less fracturing fluid flowback but high-gas production phenomenon" during shale gas drainage. In this paper, the double pressure funnels (one funnel is formed during fracturing by pressure difference from wellbore to formation, and two funnels are formed during flowback by pressure difference from fracture to formation and from fracture to wellbore) and gas-liquid two-way mass transfer (gas transfer by diffusion and liquid transfer by pressure difference) in shale gas drainage are investigated by calculating the pressure distribution after fracturing shale gas wells. The discrete numerical simulation by using unstructured PEBI grid is conducted, and the result is as follows: when shale gas well is shut-in for 20 days and produce for 1 year, the daily gas production corresponding to fracturing fluid flowback rates of 20%, 10%, and 5% are 47700 m3, 5800 m3, and 72700 m3, respectively. The investigation of double pressure funnels and gas-liquid two-way mass transfer explains clearly the phenomenon "less fracturing fluid flowback but high-gas production." Meanwhile, the two conditions for optimizing the well shut-in time after fracturing are presented. That is, as for the studied case, the moving speed of the pressure boundary line should be less than 0.1 m/d, and the water-gas ratio near the fracture should be less than 1 / d with time. Consequently, the reasonable well shut-in time is optimized to be 20-25 days. The findings in this work are of benefit to enrich the flowback theory of shale gas after fracturing and provide a theoretical basis for the optimization technology of shale gas drainage after fracturing. [ABSTRACT FROM AUTHOR]

Many biological processes involve active transport where the desired substances can be transported against the concentration gradient with energy consumption. This feature is highly desirable for the synthesis of yolk‐shell structures using preformed capsules to efficiently encapsulate yolk materials. Here, the synthesis of VOx@C yolk‐shell nanospheres by biomimicking prey–predation of carnivorous Utricularia is reported. The high intrinsic frequency and superior mechanical properties of hollow mesoporous carbon spheres (HMCS) maintain their integrity during ultrasonication, making HMCS an ideal capsule. Numerical simulation elucidates that the encapsulation of the VOx nanoparticles is ascribed to the periodic change of pressure and the damping force generated from the relative motion between the mesoporous tunnel in the HMCS and VOx nanoparticles. The resulting VOx@C yolk‐shell nanospheres demonstrate promising application as a regenerative polysulfide‐scavenging layer (RSL) for high‐loading LiS batteries (≈5 mAh cm−2). As compared with the cells with a commercial Celgard polypropylene (PP) separator, those with a RSL present improved capacity retention from 467 to 860 mAh g−1 after 100 cycles, superior rate capability, and reduced impedance. This method provides an additional synthesis tool for yolk‐shell materials otherwise inaccessible by conventional methods with potential applications in energy storage and conversion devices. [ABSTRACT FROM AUTHOR]

Background and Objective: Periodontitis (PD), a chronic infectious inflammatory disease initiated by bacteria, is associated with several local contributing factors including occlusal trauma. Previous studies have found that the traumatic occlusal force could aggravate alveolar bone loss during PD. However, the effect of reduced occlusal force during PD remains unclear. This study aimed to explore the effect of occlusal force unloading on PD onset and progression and its underlying mechanism as an effort to provide restoration suggestions for PD patients with dentition defect in clinic. This study might also propose occlusal force unloading could be a new local contributing factor for PD. Materials and Methods: C57BL/6 mice were used to establish a PD model by the ligation of 5–0 silk around the mandibular left first molar (PD group) and an unloading experiment model by the extraction of their left maxillary first molar (EX group). The THP‐1‐derived macrophages were used to verify in vivo results. Results: Micro‐CT scanning and H&E staining results consistently showed that PD + EX group experienced the most severe alveolar bone resorption as compared to PD group and control group. Further RNA‐sequencing analysis suggested that occlusal force unloading significantly enhanced osteoclastic resorption, inhibited osteoblastic activity, and promotes M1 and M2 macrophages polarization. Immunofluorescence staining (IF) results showed that compared with the PD group, PD + EX group significantly increased the ratio of M1/M2 polarization. Similar results were observed by RT‐qPCR and IF in vitro: removal of compressive force led to an increased ratio of M1/M2 polarization in LPS‐stimulated THP‐1‐derived macrophages. Conclusions: Our study demonstrated that occlusal force unloading aggravates bone resorption by increasing the ratio of M1/M2 macrophages polarization during PD, suggesting a previously unknown local contributing factor for PD, and providing a novel insight for dentists to restore missing teeth as an effort to maintain remaining dentition. [ABSTRACT FROM AUTHOR]

Exosomes derived from natural killer (NK) cells (NEO) constitute promising antineoplastic nano‐biologics because of their versatile functions in immune regulation. However, a significant augment of their immunomodulatory capability is an essential need to achieve clinically meaningful treatment outcomes. Light‐activatable silencing NK‐derived exosomes (LASNEO) are orchestrated by engineering the NEO with hydrophilic small interfering RNA (siRNA) and hydrophobic photosensitizer Ce6. Profiling of genes involved in apoptosis pathway with Western blot and RNA‐seq in cells receiving NEO treatment reveals that NEO elicits effective NK cell‐like cytotoxicity toward tumor cells. Meanwhile, reactive oxygen species (ROS) generation upon laser irradiation not only triggers substantial photodynamic therapy effect but also boosts M1 tumor‐associated macrophages polarization and DC maturation in the tumor microenvironment (TME). In addition, ROS also accelerates the cellular entry and endosomal escape of siRNA in TME. Finally, siRNAs targeting PLK1 or PD‐L1 induce robust gene silencing in cancer cells, and downregulation of PD‐L1 restores the immunological surveillance of T cells in TME. Therefore, the proposed LASNEO exhibit excellent antitumor effects by conscripting multiple types of immune cells. Considering that its manufacture is quite simple and controllable, LASNEO show compelling potential for clinical translational application. [ABSTRACT FROM AUTHOR]

Experimental observations reveal the existence of anoxic microzones within oxygen‐rich aquatic sediments. The microzones are hotspots of enhanced removal of nitrate and production of greenhouse gas nitrous oxide. Here we established a new microscale flow, reactive transport and biofilm growth model and explore how anoxic microzones form and evolve within hyporheic zones under dynamic interactions among pore‐scale flow, reactive transport and biofilm growth. The microzones can form and evolve by two patterns as streambeds are progressively clogged due to biofilm growth: (a) physical and biogeochemical conditions‐dependent perennial microzones for permeable biofilms, and (b) physical and biogeochemical conditions‐independent ephemeral microzones for low permeability biofilms. During biofilm growth, persistent transport‐dominated systems sustain for the former, whereas the transformation of transport‐dominated to reaction‐dominated systems occurs for the latter. These findings are significantly different from previous single pattern of ephemeral microzones. Plain Language Summary: Stream water is typically rich in oxygen and nutrients such as organic carbon, nitrate. Some proportion of stream water enters streambed at an upstream location of the water‐sediment interface and then exits at a downstream location. Along the subsurface flow path, oxygen concentration gradually decreases due to microbial consumption, and thus the subsurface flow zone can often be divided as generally oxic and anoxic zones. Recent studies have indicated that anoxic microzones can form within the generally oxic zone, and the microzones are the hotspots of enhanced removal of nitrate and production of greenhouse gas nitrous oxide. Here, from the microscopic view, we apply computer model to investigate how the microzones develop and change over time and space. As microbial biomass grows and streambeds are progressively clogged, the microzones can form and change following two distinct patterns depending on the streambed biofilms in which the microbes reside. Specifically, the microzones can be perennial for well permeable biofilms, whereas the microzones are ephemeral for low permeability biofilms because the microzones would disappear and an anoxic macrozone forms across the streambed. Key Points: Both the patterns of perennial and ephemeral anoxic microzones likely occur as streambeds are gradually clogged due to biofilm growthPermeable biofilms can support perennial microzones, whereas low permeability biofilms‐induced severe bioclogging lead to ephemeral onesPersistent transport‐dominated hyporheic system during biofilm growth is an essential prerequisite for presence of perennial microzones [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The arylation of C(sp3) − H bonds has been a priority research topic in organic synthesis. Minsici reactions have been the powerful methods for C(sp3) − C(sp2) bonds formation. Despite its mature development, the scopes of arenes are usually suitable for electron‐deficient heterocyclic compounds, rather than electron‐rich arenes. Herein, we report an electrooxidation‐induced alkylation of electron‐rich arenes with H2 evolution under exogenous oxidant‐free conditions, avoiding the utilization of metal catalysts. This protocol is well performed with various electron‐rich aniline derivatives and nitrogen‐containing heterocyclic compounds. We anticipate that this electro‐oxidative C(sp3) − H arylation represents an important expansion for the classic arenes alkylation, thereby proving an attractive strategy for the developments of radical cross‐coupling chemistry. [ABSTRACT FROM AUTHOR]

Metabolic interventions via targeting intratumoral dysregulated metabolism pathways have shown promise in reinvigorating antitumor immunity. However, approved small molecule immunomodulators often suffer from ineffective response rates and severe off‐target toxicity. ATP occupies a crucial role in energy metabolism of components that form the tumor microenvironment (TME) and influences cancer immunosurveillance. Here, a nanocarrier‐assisted immunometabolic therapy strategy that targets the ATP‐adenosine axis for metabolic reprogramming of TME is reported. An ecto‐enzyme (CD39) antagonist POM1 and AMP‐activated protein kinase (AMPK) agonist metformin are both encapsulated into cancer cell‐derived exosomes and used as nanocarriers for tumor targeting delivery. This method increases the level of pro‐inflammatory extracellular ATP (eATP) while preventing the accumulation of immunosuppressive adenosine and alleviating hypoxia. Elevated eATP triggers the activation of P2X7‐NLRP3‐inflammasome to drive macrophage pyroptosis, potentiates the maturation and antigen capacity of dendritic cells (DCs) to enhance the cytotoxic function of T cells and natural killer (NK) cells. As a result, synergistic antitumor immune responses are initiated to suppress tumor progress, inhibit tumor distant metastases, provide long‐term immune memory that offers protection against tumor recurrence and overcome anti‐PD1 resistance. Overall, this study provides an innovative strategy to advance eATP‐driven antitumor immunity in cancer therapy. [ABSTRACT FROM AUTHOR]

Background and Objective: Occlusal trauma is considered to be a contributing factor to bone loss associated with inflammatory periodontal disease. We hypothesized that pyroptosis, a recently discovered inflammation‐induced programmed cell death pathway, plays a role in occlusal trauma. Materials and Methods: The occlusal trauma model was established using a cemented 1‐mm elevated computer‐aided design and manufacturing (CAD/CAM) metal crown. The periodontitis model was established by periodontal wire ligation with lipopolysaccharide (LPS) injection. The rats were sacrificed at 1, 2, 3, and 4 weeks. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was used to analyze the expression of pyroptosis‐, inflammation‐, and osteoclast‐related markers. Micro‐computed tomography (micro‐CT) was used to determine bone morphology parameters. Tissue morphology was evaluated using hematoxylin and eosin staining (H&E). Osteoclasts were identified using tartrate‐resistant acid phosphatase (TRAP) staining. The expression and distribution of factors related to pyroptosis and inflammation were evaluated by immunohistochemistry (IHC). The colocalization of dead cells and cysteinyl aspartate–specific proteinase‐1 (caspase‐1)‐positive cells was analyzed by immunofluorescence. Results: Quantitative real‐time polymerase chain reaction and IHC results showed that occlusal trauma induced the expression of pyroptotic factors during the early stages, while occlusal trauma with periodontitis upregulated the expression of pyroptotic factors at the later stages. The results of qRT‐PCR, TRAP staining, and micro‐CT showed that occlusal trauma with periodontitis increased the production of proinflammatory cytokines, leading to severe bone loss. Glyburide, an NOD‐like receptor pyrin domain containing protein 3 (NLRP3)inhibitor, reduced the expression of pyroptosis markers induced by occlusal trauma with periodontitis and reversed bone resorption. Conclusions: Pyroptosis was involved in bone loss induced by occlusal trauma with or without periodontitis, while glyburide reversed inflammation and bone resorption. [ABSTRACT FROM AUTHOR]

Subcellular organelles play an indispensable role in various biological process. Therefore, it is very important to develop fluorescent probe to identify different organelles and their dynamics in specific biological processes. Herein, a new fluorescent probe has been prepared, which can be used to visualize cell death via targeting mitochondria and lipid droplets (LDs) in dual‐emission channels. The new probe appeared in the form of ring‐open in mitochondria to emit strong yellow fluorescence in living cells, while it carried out intramolecular spiral cyclization reaction to target LDs and give a cyan emission in dead cells. The performance of cell death in the UV‐exposure, lipopolysaccharide and hydrogen peroxide treatment is successfully revealed by the probe. The probe has great potential in dual colour biomedical imaging of dynamic changes of mitochondria and LDs in biological processes. [ABSTRACT FROM AUTHOR]

Background. Pancreatic cancer is a highly malignant solid tumor with a high lethality rate, but there is a lack of clinical biomarkers that can assess patient prognosis to optimize treatment. Methods. Gene-expression datasets of pancreatic cancer tissues and normal pancreatic tissues were obtained from the GEO database, and differentially expressed genes analysis and WGCNA analysis were performed after merging and normalizing the datasets. Univariate Cox regression analysis and Lasso Cox regression analysis were used to screen the prognosis-related genes in the modules with the strongest association with pancreatic cancer and construct risk signatures. The performance of the risk signature was subsequently validated by Kaplan–Meier curves, receiver operating characteristic (ROC), and univariate and multivariate Cox analyses. Result. A three-gene risk signature containing CDKN2A, BRCA1, and UBL3 was established. Based on KM curves, ROC curves, and univariate and multivariate Cox regression analyses in the TRAIN cohort and TEST cohort, it was suggested that the three-gene risk signature had better performance in predicting overall survival. Conclusion. This study identifies a three-gene risk signature, constructs a nomogram that can be used to predict pancreatic cancer prognosis, and identifies pathways that may be associated with pancreatic cancer prognosis. [ABSTRACT FROM AUTHOR]

River water flowing into and out of riparian aquifers driven by stage fluctuations during floods is critical for streamflow and biogeochemical cycling of hyporheic zones. Previous studies paid limited attention to the complex exchange flow between rivers and the adjacent unconfined aquifers through irregular and semipervious banks which are commonly seen in nature. This study proposed a new semi‐analytical solution for describing the river‐aquifer exchange flow by incorporating river stage hydrograph, and semipervious banks with irregular geometries. The solution was verified by comparing with the numerical solutions of the one‐dimensional Boussinesq equation and two‐dimensional variably saturated flow models. The comparisons indicated that the semi‐analytical solution was robust to closely approximate the bank storage exchange flow through an irregular and semipervious bank. Moreover, an innovative dimensionless river bank index (BI) was proposed to quantitively identify the importance of riverbank geometry irregularity. BI = 0.4 and BI = 0.76 are the critical threshold values to determine whether realistic bank geometry should be incorporated or not. Specifically, when BI is less than 0.4, the conventionally vertical bank can be applied to substitute realistic irregular riverbanks; When BI is greater than 0.76, however, realistic bank geometries should be included and otherwise significant errors may occur, especially when BI is much greater than 0.76. The semi‐analytical solution and BI have been successfully applied to the Hanford Reach of Columbia River, Washington, USA. The proposed solution and BI are useful for conceptual and diagnostic analysis of bank storage exchange flow and for understanding which factors and responses are important. Key Points: New mathematical model and semi‐analytical solution are developed for bank storage exchange flow with irregular and semipervious banksAn innovative dimensionless number (river bank index) is proposed to quantify the influence of bank irregularityOver‐simplified approximations of irregular bank geometry may result in non‐negligible estimation errors [ABSTRACT FROM AUTHOR]

Effective delivery of anticancer drugs into the nucleus for pharmacological action is impeded by a series of intratumoral transport barriers. Despite the significant potential of magnetic nanovehicles in electromagnetic field (EF)‐activated drug delivery, modularizing a tandem magnetoresponsive activity in a one‐nanoparticle system to meet different requirements at both tissue and cellular levels remain highly challenging. Herein, a strategy is described by employing sequential EF frequencies in inducing a succession of magnetoresponses in the magnetic nanovehicles that aims to realize cascaded tissue penetration and nuclear accumulation. This nanovehicle features ferrimagnetic vortex‐domain iron oxide nanorings coated with a thermo‐responsive polyethylenimine copolymer (PI/FVIOs). It is shown that the programmed cascading of low frequency (Lf)‐EF‐induced magnetophoresis and medium frequency (Mf)‐EF‐stimulated magneto‐thermia can steer the Doxorubicin (DOX)‐PI/FVIOs to the deep tissue and subsequently trigger intracellular burst release of DOX for successful nuclear entry. By programming the order of different EF frequencies, it is demonstrated that first‐stage Lf‐EF and subsequent Mf‐EF operation enables DOX‐PI/FVIOs to effectively deliver 86.2% drug into the nucleus in vivo. This nanodelivery system empowers potent antitumoral activity in various models of intractable tumors, including DOX‐resistant MCF‐7 breast cancer cells, triple‐negative MDA‐MB‐231 breast cancer cells, and BxPC‐3 pancreatic cancer cells with poor permeability. [ABSTRACT FROM AUTHOR]