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Magnesium (Mg) alloys have gained recognition as revolutionary biomaterials, owing to their inherent degradability, favorable biocompatibility and mechanical properties. Additive manufacturing (AM) provides high design flexibility and enables the creation of implants with personalized complex shapes and internal porous structures tailored to individual anatomical and functional needs. Particularly, laser powder bed fusion (LPBF), one prevalent AM technique, utilizes a fine laser beam as heat source and results in tiny molten pool with extremely fast cooling rate, which effectively restricts grain growth, inter-metallic precipitation and macroscopic segregation, thus facilitating the fabrication of high-performance metal parts. This review critically assesses the significance of biodegradable Mg alloys and investigates the feasibility of utilizing LPBF for Mg alloys applications in biomedical field. Detailed discussions on LPBF-processed biomedical Mg alloys parts cover process parameters, microstructure, metallurgical defects, and properties like mechanical performance, corrosion behavior, and biological response in both as-built and post-processed states. Additionally, suggestions for advancing knowledge in LPBF of biodegradable Mg alloys for biomedical applications are highlighted to propel further research and development in this field. The necessity and progress in laser powder bed fusion of biodegradable Mg alloys were elucidated. The relationship between process, formability and microstructure was reviewed. The mechanism behind microstructure evolution and performance regulation was discussed. The future challenges and upcoming research directions were provided.

Eye tracking techniques enable high-efficient, natural, and effortless human-machine interaction by detecting users’ eye movements and decoding their attention and intentions. Here, a miniature, imperceptible, and biocompatible smart contact lens is proposed for in situ eye tracking and wireless eye-machine interaction. Employing the frequency encoding strategy, the chip-free and battery-free lens successes in detecting eye movement and closure. Using a time-sequential eye tracking algorithm, the lens has a great angular accuracy of <0.5°, which is even less than the vision range of central fovea. Multiple eye-machine interaction applications, such as eye-drawing, Gluttonous Snake game, web interaction, pan-tilt-zoom camera control, and robot vehicle control, are demonstrated on the eye movement model and in vivo rabbit. Furthermore, comprehensive biocompatibility tests are implemented, demonstrating low cytotoxicity and low eye irritation. Thus, the contact lens is expected to enrich approaches of eye tracking techniques and promote the development of human-machine interaction technology. Eye tracking techniques enable high-efficient, natural, and effortless human-machine interaction. Here, Zhu et al. proposed a contact lens to track eye movement for wireless eye-machine interaction

Surgery represents a primary clinical treatment of solid tumors. The high risk of local relapse typically requires frequent hospital visits for postoperative adjuvant therapy. Here, device designs and system integration of a stretchable electronic device for wearable cancer treatment are presented. The soft electronic patch harnesses compliant materials to achieve conformal and stable attachment to the surgical wound. A composite nanotextile dressing is laminated to the electronic patch to allow the on‐demand release of anticancer drugs under electro‐thermal actuation. An additional flexible circuit and a compact battery complete an untethered wearable system to execute remote therapeutic commands from a smartphone. The successful implementation of combined chemothermotherapy to inhibit tumor recurrence demonstrates the promising potential of stretchable electronics for advanced wearable therapies without interfering with daily activities. A stretchable electronic patch is integrated into a self‐powered platform for skin‐attached administration of synergistic chemothermotherapy under remote commands from a smartphone. The successful inhibition of postoperative recurrence demonstrates the promising potential of stretchable electronic devices for wearable cancer treatment without interfering with daily activities.

Cisplatin is a widely applied therapeutics for the treatment of osteosarcoma. However, its clinical applications have been hindered due to low efficacy and bioavailability, and particularly frequent emergence of reactive oxygen species (ROS)-decrease induced drug resistance. The transcription factor NF-E2-related factor 2 (Nrf2) is increased in cancer patients and induces poor outcome in osteosarcoma treatment, making it a novel target to improve the efficacy of chemotherapy. Herein, a hyaluronidase-responsive multi-layer liposome (HLCN) for co-delivery of cisplatin and Nrf2 siRNA (siNrf2) is developed. It is composed of Vpr 52-96 modified liposome covered with hyaluronic acid (HA). HLCN selectively accumulates in osteosarcoma by targeting tumor-specific CD44, and can be degraded by endosomal hyaluronidase to generate cationic liposome, which promotes the endosomal escape of Vpr 52-96 , cisplatin and siNrf2. HLCN can effectively decrease Nrf2 level, promote ROS generation, activate itochondrial apoptotic pathway, and consequently enhance anticancer efficacy of cisplatin. Particularly, HLCN shows high cytotoxicity to osteosarcoma cells with an IC 50 value of about 1 µM, which is four-fold lower than liposomal cisplatin (IC 50 4 µM), indicating that Nrf2 silence can significantly improve cisplatin sensitivity in cancer cells. Importantly, HLCN can remarkably inhibit tumor growth in the xenograft osteosarcoma mice with minimal systemic adverse effects. Therefore, this novel stimuli-responsive combination therapy of cisplatin and siNrf2 provides a promising strategy for the treatment of osteosarcoma.

Stimuli-responsive delivery systems hold promise in cancer treatments. However, their application potential has been limited due to undesirable drug leaking during blood circulation and inefficient therapeutic efficacy in tumors, resulting in undesirable therapeutic outcomes. Herein, we have developed a novel redox-sensitive pegylated phospholipid, termed as DOPE-SS-PEG, which can form a glutathione (GSH)-triggered precision explosive system (GPS) for simultaneously improving circulation stability, tumor specificity, and chemosensitivity, leading to explosive anticancer effects. GPS is constructed of liposomal doxorubicin (DOX) functionalized with DOPE-SS-PEG and MnO 2 nanoparticles, which can protect liposome structure in the presence of serum GSH (20 pM), whereas converts to cationic liposome in response to intracellular GSH (10 mM), thereby enhancing circulation stability, tumor specificity, endosomal escape, and cytoplasmic delivery. Importantly, GPS can not only generate oxygen to relieve hypoxia and consequently enhance chemosensitivity, but quench GSH antioxidability to elevate the accruement of intracellular reactive oxygen species (ROS), leading to an explosion of oxidative stress induced cell injury. Particularly, in vivo studies show that GPS selectively accumulates in tumor tissues, effectively inhibits tumor growth, exhibits minimal systemic adverse effects, and consequently prolongs the survival time of tumor-bearing mice. Therefore, GPS is a unique stimuli-responsive treatment with programmed and on-demand drug delivery, as well as explosive therapeutic efficacy, and provides an intelligent anticancer treatment.

For the realization of bioassay with complex fluidic manipulation and logic operation on lab-on-a-disc platform, we present an active integrated centrifugal microfluidic chip based on the on-board control of wax valves within a multilayer complex chip. The multilayer hybrid structure including a microfluidic layer and a printing circuit board (PCB) layer utilizes the digital logic of electronic system to control the logic of liquid flow in microfluidic layer. The coupling mechanism between both layers is based on heat transfer, namely, the heating resistors in PCB layer are used to melt and open the paraffin wax valves in microfluidic layer. Without the limitation of surface tension-dependent valves, the application of active valve could be freely designed, which can largely extend the ability of integration on microfluidic chip. Many complex functional units including liquid sequential loading and switching of liquid flow are demonstrated. As an application, we also present a multilayer complex chip for plasmid DNA extraction based on our platform. In a word, our active centrifugal microfluidic platform provides a solution for the integration of complex bioassay on rotating disc, which has great potential in the applications of point-of-care diagnostics (POC).

RNA interference mediated by small interfering RNA (siRNA) provides a powerful tool for gene regulation, and has a broad potential as a promising therapeutic strategy. However, therapeutics based on siRNA have had limited clinical success due to their undesirable pharmacokinetic properties. This study presents pH‐sensitive nanoparticles‐based siRNA delivery systems (PNSDS), which are positive‐charge‐free nanocarriers, composed of siRNA chemically crosslinked with multi‐armed poly(ethylene glycol) carriers via acid‐labile acetal linkers. The unique siRNA crosslinked structure of PNSDS allows it to have minimal cytotoxicity, high siRNA loading efficiency, and a stimulus‐responsive property that enables the selective intracellular release of siRNA in response to pH conditions. This study demonstrates that PNSDS can deliver tumor necrosis factor alpha (TNF‐α) siRNA into macrophages and induce the efficient down regulation of the targeted gene in complete cell culture media. Moreover, PNSDS with mannose targeting moieties can selectively accumulate in mice liver, induce specific inhibition of macrophage TNF‐α expression in vivo, and consequently protect mice from inflammation‐induced liver damages. Therefore, this novel siRNA delivering platform would greatly improve the therapeutic potential of RNAi based therapies. A pH‐sensitive nanoparticle‐based small interfering RNA (siRNA) delivery system (PNSDS) is developed. PNSDS is a positive‐charge‐free nanocarrier, composed of siRNA chemically crosslinked with multi‐armed poly(ethylene glycol) carriers via acid‐labile acetal linkers. PNSDS with mannose targeting moieties can selectively accumulate in mice liver, induce specific inhibition of macrophage TNF‐α expression in vivo, and consequently protect mice from inflammation‐induced liver damages.

The in vivo optical detection of bacterial infections requires highly specific imaging probes with small affinity to mammalian tissue. It is now shown that fluorescent dyes that are conjugated to maltohexaose can be internalized rapidly via the bacteria-specific maltodextrin transport pathway, enabling the in vivo imaging of Escherichia coli down to 10 5 colony-forming units. The diagnosis of bacterial infections remains a major challenge in medicine. Although numerous contrast agents have been developed to image bacteria, their clinical impact has been minimal because they are unable to detect small numbers of bacteria in vivo , and cannot distinguish infections from other pathologies such as cancer and inflammation 1 , 2 , 3 , 4 , 5 , 6 , 7 . Here, we present a family of contrast agents, termed maltodextrin-based imaging probes (MDPs), which can detect bacteria in vivo with a sensitivity two orders of magnitude higher than previously reported, and can detect bacteria using a bacteria-specific mechanism that is independent of host response and secondary pathologies. MDPs are composed of a fluorescent dye conjugated to maltohexaose, and are rapidly internalized through the bacteria-specific maltodextrin transport pathway 8 , 9 , 10 , 11 , endowing the MDPs with a unique combination of high sensitivity and specificity for bacteria. Here, we show that MDPs selectively accumulate within bacteria at millimolar concentrations, and are a thousand-fold more specific for bacteria than mammalian cells. Furthermore, we demonstrate that MDPs can image as few as 10 5 colony-forming units in vivo and can discriminate between active bacteria and inflammation induced by either lipopolysaccharides or metabolically inactive bacteria.

Early control of elevated blood pressure is the most promising treatment for acute intracerebral haemorrhage. We aimed to establish whether implementing a goal-directed care bundle incorporating protocols for early intensive blood pressure lowering and management algorithms for hyperglycaemia, pyrexia, and abnormal anticoagulation, implemented in a hospital setting, could improve outcomes for patients with acute spontaneous intracerebral haemorrhage. We performed a pragmatic, international, multicentre, blinded endpoint, stepped wedge cluster randomised controlled trial at hospitals in nine low-income and middle-income countries (Brazil, China, India, Mexico, Nigeria, Pakistan, Peru, Sri Lanka, and Viet Nam) and one high-income country (Chile). Hospitals were eligible if they had no or inconsistent relevant, disease-specific protocols, and were willing to implement the care bundle to consecutive patients (aged ≥18 years) with imaging-confirmed spontaneous intracerebral haemorrhage presenting within 6 h of the onset of symptoms, had a local champion, and could provide the required study data. Hospitals were centrally randomly allocated using permuted blocks to three sequences of implementation, stratified by country and the projected number of patients to be recruited over the 12 months of the study period. These sequences had four periods that dictated the order in which the hospitals were to switch from the control usual care procedure to the intervention implementation of the care bundle procedure to different clusters of patients in a stepped manner. To avoid contamination, details of the intervention, sequence, and allocation periods were concealed from sites until they had completed the usual care control periods. The care bundle protocol included the early intensive lowering of systolic blood pressure (target <140 mm Hg), strict glucose control (target 6·1–7·8 mmol/L in those without diabetes and 7·8–10·0 mmol/L in those with diabetes), antipyrexia treatment (target body temperature ≤37·5°C), and rapid reversal of warfarin-related anticoagulation (target international normalised ratio <1·5) within 1 h of treatment, in patients where these variables were abnormal. Analyses were performed according to a modified intention-to-treat population with available outcome data (ie, excluding sites that withdrew during the study). The primary outcome was functional recovery, measured with the modified Rankin scale (mRS; range 0 [no symptoms] to 6 [death]) at 6 months by masked research staff, analysed using proportional ordinal logistic regression to assess the distribution in scores on the mRS, with adjustments for cluster (hospital site), group assignment of cluster per period, and time (6-month periods from Dec 12, 2017). This trial is registered at Clinicaltrials.gov (NCT03209258) and the Chinese Clinical Trial Registry (ChiCTR-IOC-17011787) and is completed. Between May 27, 2017, and July 8, 2021, 206 hospitals were assessed for eligibility, of which 144 hospitals in ten countries agreed to join and were randomly assigned in the trial, but 22 hospitals withdrew before starting to enrol patients and another hospital was withdrawn and their data on enrolled patients was deleted because regulatory approval was not obtained. Between Dec 12, 2017, and Dec 31, 2021, 10 857 patients were screened but 3821 were excluded. Overall, the modified intention-to-treat population included 7036 patients enrolled at 121 hospitals, with 3221 assigned to the care bundle group and 3815 to the usual care group, with primary outcome data available in 2892 patients in the care bundle group and 3363 patients in the usual care group. The likelihood of a poor functional outcome was lower in the care bundle group (common odds ratio 0·86; 95% CI 0·76–0·97; p=0·015). The favourable shift in mRS scores in the care bundle group was generally consistent across a range of sensitivity analyses that included additional adjustments for country and patient variables (0·84; 0·73–0·97; p=0·017), and with different approaches to the use of multiple imputations for missing data. Patients in the care bundle group had fewer serious adverse events than those in the usual care group (16·0% vs 20·1%; p=0·0098). Implementation of a care bundle protocol for intensive blood pressure lowering and other management algorithms for physiological control within several hours of the onset of symptoms resulted in improved functional outcome for patients with acute intracerebral haemorrhage. Hospitals should incorporate this approach into clinical practice as part of active management for this serious condition. Joint Global Health Trials scheme from the Department of Health and Social Care, the Foreign, Commonwealth & Development Office, and the Medical Research Council and Wellcome Trust; West China Hospital; the National Health and Medical Research Council of Australia; Sichuan Credit Pharmaceutic and Takeda China.

In order to make it clear for explosion accidents of parallel capacitors occurred in 500kV substations in Sichuan power network one after another, the authors calculate and analyze the distribution of overvoltage caused by breakdown of elements within the capacitor bank. Dissecting the insulation of faulty capacitors, severe ageing of insulation is discovered; this phenomenon proves that the overvoltage on partial element should be the main factor influencing the insulating performance of capacitors. To ensure the reliable operation of parallel capacitors the setting value of unbalanced current protection at the neutral point of double star connection is modified by the calculated value of unbalanced current of 35kV capacitor bank in which there are six parallel groups of capacitors and in each group seven capacitors are connected in series.