Anion-modulated Ion Conductor with Chain Conformational Transformation for stabilizing Interfacial Phase of High-Voltage Lithium Metal Batteries.

In solid-state lithium metal batteries (SSLMBs), the inhomogeneous electrolyte-electrode interphase layer aggravates the interfacial stability, leading to discontinuous interfacial ion/charge transport and continuous degradation of the electrolyte. Herein, we constructed an anion-modulated ionic conductor (AMIC) that enables in situ construction of electrolyte/electrode interphases for high-voltage SSLMBs by exploiting conformational transitions under multiple interactions between polymer and lithium salt anions. Anions modulate the decomposition behavior of supramolecular poly (vinylene carbonate) (PVC) at the electrode interface by changing the spatial conformation of the polymer chains, which further enhances ion transport and stabilizes the interfacial morphology. In addition, the AMIC weakens the "Li+-solvation" and increases Li+ vehicle sites, thereby enhancing the lithium-ion transport number (tLi +=~0.67). Consequently, Li || LiNi0.8Co0.1Mn0.1O2 cell maintains about 85 % capacity retention and Coulombic efficiency >99.8 % in 200 cycles at a charge cut-off voltage of 4.5 V. This study provides a new understanding of lithium salt anions regulating polymer chain segment behavior in the solid-state polymer electrolyte (SPE) and highlights the importance of the ion environment in the construction of interfacial phases and ionic conduction.

IL-37 Represses the Autoimmunity in Myasthenia Gravis via Directly Targeting Follicular Th and B Cells.

IL-37 is a newly identified immune-suppressive factor; however, the function, cellular sources, and mechanism of IL-37 in humoral immunity and Myasthenia gravis (MG) are still unclear. In this study, we found IL-37 were substantially downregulated in the serum and PBMCs of MG patients compared with healthy controls. The lower IL-37 was associated with severer disease (quantitative MG score) and higher follicular Th (Tfh)/Tfh17 and B cell numbers. Flow cytometry analysis revealed that IL-37 was mainly produced by CD4+ T cells without overlapping with Th1, Th17, and Tfh subsets in MG patients. Regulatory IL-37+ T cell rarely expressed Foxp3 and CD25 but produced numerous IL-4. Tfh and B cell expressed high levels of SIGIRR, the receptor of IL-37, in MG patients. Mechanically, IL-37 directly bond to SIGIRR, repressed the proliferation, cytokine production of Tfh and B cells, and the secretion of autoantibody via inhibition of STAT3 signaling in Tfh and B cells.

Double-negative T cells remarkably promote neuroinflammation after ischemic stroke.

CD3+CD4-CD8- T cells (double-negative T cells; DNTs) have diverse functions in peripheral immune-related diseases by regulating immunological and inflammatory homeostasis. However, the functions of DNTs in the central nervous system remain unknown. Here, we found that the levels of DNTs were dramatically increased in both the brain and peripheral blood of stroke patients and in a mouse model in a time-dependent manner. The infiltrating DNTs enhanced cerebral immune and inflammatory responses and exacerbated ischemic brain injury by modulating the FasL/PTPN2/TNF-α signaling pathway. Blockade of this pathway limited DNT-mediated neuroinflammation and improved the outcomes of stroke. Our results identified a critical function of DNTs in the ischemic brain, suggesting that this unique population serves as an attractive target for the treatment of ischemic stroke.

Self-Propagating Enabling High Lithium Metal Utilization Ratio Composite Anodes for Lithium Metal Batteries.

Constructing three-dimensional (3D) structural composite lithium metal anode by molten-infusion strategy is an effective strategy to address the severe problems of Li dendritic growth and huge volume changes. However, various challenges, including uncontrollable Li loading, dense inner structure, and low Li utilization, still need to be addressed for the practical application of 3D Li anode. Herein, we propose a self-propagating method, which is realized by a synergistic effect of chemical reaction and capillarity effect on porous scaffold surface, for fabricating a flexible 3D composite Li metal anode with high Li utilization ratio and controllable low Li loading. The composite 3D anode possesses controllable low loading (8.0-24.0 mAh cm-2) and uniform grid structure, realizing a stable cycling over 600 h at a high Li metal utilization ratio over 75%. The proposed strategy for fabricating composite 3D anode could promote the practical application of Li metal batteries.

Prelithiated V2 C MXene: A High-Performance Electrode for Hybrid Magnesium/Lithium-Ion Batteries by Ion Cointercalation.

The pursuit of high reversible capacity and long cycle life for rechargeable batteries has gained extensive attention in recent years, and the development of applicable electrode materials is the key point. Herein, thanks to the preintercalation of lithium ions, a stable and highly conductive nanostructure of V2 C MXene is successfully fabricated via a facile self-discharge mechanism, which provides open spaces for rapid ion diffusion and guarantees fast electron transport. Taking the prelithiated V2 C as electrode, an outstanding initial coulombic efficiency of 80% and an impressive capacity retention of ≈98% after 5000 charge/discharge cycles are achieved for lithium-ion batteries. Especially, it demonstrates a fascinating reversible capacity of up to 230.3 mA h g-1 at 0.02 A g-1 and a long cycling life of 82% capacity retention over 480 cycles in the hybrid magnesium/lithium-ion batteries. In addition, the Mg2+ and Li+ ions cointercalation mechanism of the prelithiated V2 C is elucidated through ex situ X-ray diffraction and X-ray photoelectron spectroscopy characterizations. This work not only offers an effective approach to compensate the large initial lithium loss of high-capacity anode materials but also opens up a new and viable avenue to develop promising hybrid Mg/Li-storage materials with eminent electrochemical performance.

Chemical Energy Release Driven Lithiophilic Layer on 1 m2 Commercial Brass Mesh toward Highly Stable Lithium Metal Batteries.

It is imperative to explore practical methods and materials to drive the development of high energy density lithium metal batteries. The constuciton of nanostructure electrodes and surface engineering on the current collectors are the two most effective strategies to regulate the homogeneous Li plating/stripping to relieve the Li dendrites and infinite volume change problems. Based on the low stacking fault energy of the Cu-Zn alloy, we present a novel chemical energy release induced surface atom diffusion strategy, which is achieved by the negative Gibbs free energy from the surface oxidation reaction and subsequent replacement reaction under thermal treatment in air, to realize a uniform upper ZnO nanoparticles coating. Furthermore, we apply the modified brass mesh as a lithiophilic current collector to decrease the Li deposition nucleation overpotential and effectively restrain the Li dendrite growth. The modified brass current collector achieves a long-term cycling stability of 500 cycles at 2.0 mA cm-2. We have verified the effectiveness of our chemical energy release modification strategy on a 1 m2 brass mesh and other Cu alloy (Tin bronze mesh), which demonstrates its great opportunities for scalable and safe lithium metal batteries.

Early Lithium Plating Behavior in Confined Nanospace of 3D Lithiophilic Carbon Matrix for Stable Solid-State Lithium Metal Batteries.

Considerable efforts are devoted to relieve the critical lithium dendritic and volume change problems in the lithium metal anode. Constructing uniform Li+ distribution and lithium "host" are shown to be the most promising strategies to drive practical lithium metal anode development. Herein, a uniform Li nucleation/growth behavior in a confined nanospace is verified by constructing vertical graphene on a 3D commercial copper mesh. The difference of solid-electrolyte interphase (SEI) composition and lithium growth behavior in the confined nanospace is further demonstrated by in-depth X-ray photoelectron spectrometer (XPS) and line-scan energy dispersive X-ray spectroscopic (EDS) methods. As a result, a high Columbic efficiency of 97% beyond 250 cycles at a current density of 2 mA cm-2 and a prolonged lifespan of symmetrical cell (500 cycles at 5 mA cm-2 ) can be easily achieved. More meaningfully, the solid-state lithium metal cell paired with the composite lithium anode and LiNi0.5 Co0.2 Mn0.3 O2 (NCM) as the cathode also demonstrate reduced polarization and extended cycle. The present confined nanospace-derived hybrid anode can further promote the development of future all solid-state lithium metal batteries.

Single-Crystal α-Fe2O3 with Engineered Exposed (001) Facet for High-Rate, Long-Cycle-Life Lithium-Ion Battery Anode.

Designing electrode materials with engineered exposed facets provides a novel strategy to improve their electrochemical properties. However, the controllability of the exposed facet remains a daunting challenge, and a deep understanding of the correlation between exposed facet and Li+-transfer behavior has been rarely reported. In this work, single-crystal α-Fe2O3 hexagonal nanosheets with an exposed (001) facet are prepared with the assistance of aluminum ions through a one-step hydrothermal process, and structural characterizations reveal an Al3+-concentration-dependent-growth mechanism for the α-Fe2O3 nanosheets. Furthermore, such α-Fe2O3 nanosheets, when used as lithium-ion battery anodes, exhibit high specific capacity (1261.3 mAh g-1 at 200 mA g-1), high rate capability (with a reversible capacity of approximately 605 mAh g-1 at 10 A g-1), and excellent cyclic stability (with a capacity of over 900 mAh g-1 during 500 cycles). The superior electrochemical performance of α-Fe2O3 nanosheets is attributed to the pseudocapacitive behavior, Al-doping in the α-Fe2O3 structure, and improved Li+-transfer property across the (001) facet, as elucidated by first-principles calculations based on density functional theory. These results reveal the underlying mechanism of Li+ transfer across different facets and thus provide insights into the understanding of the excellent electrochemical performance.

Hydrothermal synthesis of graphene/nickel oxide nanocomposites used as the electrode for supercapacitors.

Graphene (GR)-based nanocomposites with different mass ratios of NiO and GR are prepared via hydrothermal method using Ni(NO3)2 as the origin of nickel and urea as the hydrolysis-controlling agent. The morphology and electrochemical performance of the GR/NiO nanocomposites are closely associated with the mass ratios of GR to NiO. The chemical composition and morphology of the composites together with the pure GR and NiO are characterized by thermogravimetric analysis (TGA), X-ray diffraction (XRD), scanning electron microscope (SEM), and transmission electron microscope (TEM). It is found that the GR sheets and NiO particles form uniform nanocomposites with the NiO particles absorbed on the GR surface. A specific capacitance of 384 F g(-1) at a current density of 0.1 A g(-1) is achieved when the coating amount of NiO is up to 74 wt%. In addition, the attenuation of the specific capacitance is less than 6% after 500 cycles, indicating such nanocomposite has excellent cycling performance.

Stabilizing a Li1.3Al0.3Ti1.7(PO4)3/Li metal anode interface in solid-state batteries with a LiF/Cu-rich multifunctional interlayer.

Li1.3Al0.3Ti1.7(PO4)3 (LATP) has attracted much attention due to its high ionic conductivity, good air stability and low cost. However, the practical application of LATP in all-solid-state lithium batteries faces serious challenges, such as high incompatibility with lithium metal and high interfacial impedance. Herein, a CuF2 composite layer was constructed at a Li/LATP interface by a simple drop coating method. CuF2 in the interlayer reacts with lithium metal in situ to form a multifunctional interface rich in Cu and LiF. The multifunctional layer not only brings about close interfacial contact between LATP and Li metal, but also effectively prevents the electrochemical reaction of LATP with Li metal, and suppresses the electron tunneling and dendrite growth at the interface. The interfacial resistance of Li/CuF2@LATP/Li symmetric batteries is significantly reduced from 562 to 92 Ω, and the critical current density is increased to 1.7 mA cm-2. An impressive stable cycle performance of over 6000 h at 0.1 mA cm-2/0.1 mA h cm-2, 2200 h at 0.2 mA cm-2/0.2 mA h cm-2 and 1600 h at 0.3 mA cm-2/0.3 mA h cm-2 is achieved. Full batteries of LiFePO4/CuF2@LATP/Li also show a high capacity retention ratio of 80.3% after 540 cycles at 25 °C. This work provides an effective and simple composite layer solution to address the interfacial problem of Li/LATP.

Alignment of graphene sheets in wax composites for electromagnetic interference shielding improvement.

Rapid advancements in carbon-based fillers have enabled a new and more promising platform in the development of electromagnetic attenuation composites. Alignment of fillers in composites with specific structures and morphologies has been widely pursued to achieve high performance based on taking advantage of unique filler characteristics. In this work, few-layer graphene (FLG), obtained from direct exfoliation of graphite, was fabricated into paraffin wax to prepare FLG/wax composites and investigate their electromagnetic interference (EMI) shielding performance. The as-exfoliated FLG/wax samples have shown much improved EMI performance compared to the commercial graphite/wax ones. For further improvement of EMI shielding performance, split-press-merge approaches were applied to align the FLG fillers to achieve anisotropic characteristics in the plane perpendicular to the pressing direction. Much enhanced EMI shielding performance coupled with an improvement in absorption and reflection was observed in the post-alignment FLG/wax composites. An average interparticle distance model associated with improved electrically conducting interconnection and enlarged effective reflection regions with respect to enhanced reflection efficiency were discussed. The results suggest a platform and promising opportunities for preparing high-performance EMI shielding composites.

Priority and Prospect of Sulfide-Based Solid-Electrolyte Membrane.

All-solid-state lithium batteries (ASSLBs) employing sulfide solid electrolytes (SEs) promise sustainable energy storage systems with energy-dense integration and critical intrinsic safety, yet they still require cost-effective manufacturing and the integration of thin membrane-based SE separators into large-format cells to achieve scalable deployment. This review, based on an overview of sulfide SE materials, is expounded on why implementing a thin membrane-based separator is the priority for mass production of ASSLBs and critical criteria for capturing a high-quality thin sulfide SE membrane are identified. Moreover, from the aspects of material availability, membrane processing, and cell integration, the major challenges and associated strategies are described to meet these criteria throughout the whole manufacturing chain to provide a realistic assessment of the current status of sulfide SE membranes. Finally, future directions and prospects for scalable and manufacturable sulfide SE membranes for ASSLBs are presented.

Tailoring Conversion-Reaction-Induced Alloy Interlayer for Dendrite-Free Sulfide-Based All-Solid-State Lithium-Metal Battery.

Utilization of lithium (Li) metal anodes in all-solid-state batteries employing sulfide solid electrolytes is hindered by diffusion-related dendrite growth at high rates of charge. Engineering ex-situ Li-intermetallic interlayers derived from a facile solution-based conversion-alloy reaction is attractive for bypassing the Li0 self-diffusion restriction. However, no correlation is established between the properties of conversion-reaction-induced (CRI) interlayers and the deposition behavior of Li0 in all-solid-state lithium-metal batteries (ASSLBs). Herein, using a control set of electrochemical characterization experiments with LixAgy as the interlayer in different battery chemistries, this work identifies that dendritic tolerance in ASSLBs is susceptible to the surface roughness and electronic conductivity of the CRI-alloy interlayer. This work thereby tailors the CRI-alloy interlayer from the typical mosaic structure to a hierarchical gradient structure by adjusting the pit corrosion kinetics from the (de)solvation mechanism to an adsorption model, yielding a smooth organic-rich outer layer and a composition-regulated inorganic-rich inner layer composed mainly of lithiophilic LixAgy and electron-insulating LiF. Ultimately, desirable roughness, conductivity, and diffusivity are integrated simultaneously into the tailored CRI-alloy interlayer, resulting in dendrite-free and dense Li deposition beneath the interlayer capable of improving battery cycling stability. This work provides a rational protocol for the CRI-alloy interlayer specialized for ASSLBs.

Confined Lithium Deposition Triggered by an Integrated Gradient Scaffold for a Lithium-Metal Anode.

Constructing a composite lithium anode with a rational structure has been considered as an effective approach to regulate and relieve the tough problems of a sparkling Li anode. However, the potential short circuits risk that Li deposition at the surface of the framework has not yet been resolved. Here, we present a simple regulating-deposition strategy to guide the preferentially bottom-up deposition/growth of Li. The triple-gradient structure of modified porous copper with electrical passivation (top) and chemical activation (bottom) shows significant improvements in the morphological stability and electrochemical performance. Meanwhile, the in situ generation of Li2Se can as an advanced artificial SEI layer be devoted to homogeneous Li plating/stripping. As a result, the composite anode exhibits a long-term cycling over 250 cycles with a high average CE of 98.2% at 1 mA cm-2. Furthermore, a capacity retention of 94.4% in full cells can be achieved when pairing with LiFePO4 as the cathode. These results ensure a bright direction for developing high-performance Li metal anodes.

Oxygen Vacancies in Bismuth Tantalum Oxide to Anchor Polysulfide and Accelerate the Sulfur Evolution Reaction in Lithium-Sulfur Batteries.

The shuttling effect of soluble lithium polysulfides (LiPSs) and the sluggish conversion kinetics of polysulfides into insoluble Li2S2/Li2S severely hinders the practical application of Li-S batteries. Advanced catalysts can capture and accelerate the liquid-solid conversion of polysulfides. Herein, we try to make use of bismuth tantalum oxide with oxygen vacancies as an electrocatalyst to catalyze the conversion of LiPSs by reducing the sulfur reduction reaction (SRR) nucleation energy barrier. Oxygen vacancies in Bi4TaO7 nanoparticles alter the electron band structure to improve instinct electronic conductivity and catalytic activity. In addition, the defective surface could provide unsaturated bonds around the vacancies to enhance the chemisorption capability with LiPSs. Hence, a multidimensional carbon (super P/CNT/Graphene) standing sulfur cathode is prepared by coating oxygen vacancies Bi4TaO7-x nanoparticles, in which the multidimensional carbon (MC) with micropores structure can host sulfur and provide a fast electron/ion pathway, while the outer-coated oxygen vacancies with Bi4TaO7-x with improved electronic conductivity and strong affinities for polysulfides can work as an adsorptive and conductive protective layer to achieve the physical restriction and chemical immobilization of lithium polysulfides as well as speed up their catalytic conversion. Benefiting from the synergistic effects of different components, the S/C@Bi3TaO7-x coin cell cathode shows superior cycling and rate performance. Even under a high level of sulfur loading of 9.6 mg cm-2, a relatively high initial areal capacity of 10.20 mAh cm-2 and a specific energy density of 300 Wh kg-1 are achieved with a low electrolyte/sulfur ratio of 3.3 µL mg-1. Combined with experimental results and theoretical calculations, the mechanism by which the Bi4TaO7 with oxygen vacancies promotes the kinetics of polysulfide conversion reactions has been revealed. The design of the multiple confined cathode structure provides physical and chemical adsorption, fast charge transfer, and catalytic conversion for polysulfides.

[An experimental study on the safety of intratracheal drug administration].

OBJECTIVE: To explore whether injury and repair occur in the trachea and the lung after intra-tracheal administration of different drugs. METHODS: Wistar rats were randomly divided into 5 groups, a normal group, a blank control (BC) group, a normal saline (NS) group, a lidocaine (LD) group and an amikacin (AK) group. For the latter 3 groups, normal saline, lidocaine and amikacin were injected into trachea by needle puncture. Scanning electron microscope was used to observe the ultra-structural changes of the epithelium, and the percentage of the area of damage (PAD) in tracheal mucosa was calculated. Moreover, pathological changes of the mucous membrane of bronchioles and alveolar epithelial cells were also examined, and the degree of lung pathology was semi-quantified. RESULTS: Two hours after the injection of the 3 drugs, derangement and edema of the cilia were evident by scanning electron microscopy. The PAD of the NS group, the LD group and the AK group were (94.2 ± 3.2)%, (93.1 ± 3.0)% and (95.5 ± 1.8)%, respectively; all being significantly higher than that of the BC group (1.3 ± 0.3)%. For the NS group and the LD group, the PAD decreased significantly after 24 h, which were (73.7 ± 7.8)% and (81.0 ± 4.6)% respectively, and returned to normal at 48 h and 96 h. While for the AK group, the damage began to improve at 72 h [PAD (62.1 ± 5.2)%], and recovered at 96 h. Airway epithelial derangement and cell edema in the alveoli and the bronchioles also occurred 2 h after drug injection, and inflammatory cell infiltration became evident at 24 h. At this time, the score of pathology was 1.80 ± 0.84, 2.60 ± 0.55 and 2.80 ± 0.45 for the NS group, the LD group and the AK group, respectively; all being higher than that of the BC group (0). These pathological changes recovered totally after 72 h for the NS and the LD groups, and 96 h for the AK group. CONCLUSIONS: Intra-tracheal administration of normal saline, lidocaine and amikacin in rats led to reversible airway mucosal and lung tissue damages.

Boosting oxygen evolution reaction activity by tailoring MOF-derived hierarchical Co-Ni alloy nanoparticles encapsulated in nitrogen-doped carbon frameworks.

The growing demand for sustainable energy has led to in-depth research on hydrogen production from electrolyzed water, where the development of electrocatalysts is a top priority. We here report a controllable strategy for preparing the cobalt-nickel alloy nanoparticles encapsulated in nitrogen-doped porous carbon by annealing a bimetal-organic framework. The delicately tailored hierarchical Co2Ni@NC nanoparticles effectively realize abundant synergistic active sites and fast mass transfer for the oxygen evolution reaction (OER). Remarkably, the optimized Co2Ni@NC exhibits a small overpotential of 310 mV to achieve a current density of 10 mA cm-2 and an excellent long-term stability in alkaline electrolyte. Furthermore, the underlying synergistic effect mechanism of the Co-Ni model has been pioneeringly elucidated by density functional theory calculations.

Synergistic Adsorption-Catalytic Sites TiN/Ta2O5 with Multidimensional Carbon Structure to Enable High-Performance Li-S Batteries.

Lithium-sulfur (Li-S) batteries are deemed to be one of the most optimal solutions for the next generation of high-energy-density and low-cost energy storage systems. However, the low volumetric energy density and short cycle life are a bottleneck for their commercial application. To achieve high energy density for lithium-sulfur batteries, the concept of synergistic adsorptive-catalytic sites is proposed. Base on this concept, the TiN@C/S/Ta2O5 sulfur electrode with about 90 wt% sulfur content is prepared. TiN contributes its high intrinsic electron conductivity to improve the redox reaction of polysulfides, while Ta2O5 provides strong adsorption capability toward lithium polysulfides (LiPSs). Moreover, the multidimensional carbon structure facilitates the infiltration of electrolytes and the motion of ions and electrons throughout the framework. As a result, the coin Li-S cells with TiN@C/S/Ta2O5 cathode exhibit superior cycle stability with a decent capacity retention of 56.1% over 300 cycles and low capacity fading rate of 0.192% per cycle at 0.5 C. Furthermore, the pouch cells at sulfur loading of 5.3 mg cm-2 deliver a high areal capacity of 5.8 mAh cm-2 at low electrolyte/sulfur ratio (E/S, 3.3 µL mg-1), implying a high sulfur utilization even under high sulfur loading and lean electrolyte operation.

Synthetic VSMCs induce BBB disruption mediated by MYPT1 in ischemic stroke.

Vascular smooth muscle cells (VSMCs) have been widely recognized as key players in regulating blood-brain barrier (BBB) function, and their roles are unclear in ischemic stroke. Myosin phosphatase target subunit 1 (MYPT1) is essential for VSMC contraction and maintaining healthy vasculature. We generated VSMC-specific MYPT1 knockout (MYPT1SMKO) mice and cultured VSMCs infected with Lv-shMYPT1 to explore phenotypic switching of VSMCs and the accompanied impacts on BBB integrity. We found that MYPT1 deficiency induced phenotypic switching of synthetic VSMCs, which aggravated BBB disruption. Proteomic analysis identified evolutionarily conserved signaling intermediates in Toll pathways (ECSIT) as a downstream molecule that promotes activation of synthetic VSMCs and contributed to IL-6 expression. Knocking down ECSIT rescued phenotypic switching of VSMCs and BBB disruption. Additionally, inhibition of IL-6 decreased BBB permeability. These findings reveal that MYPT1 deficiency activated phenotypic switching of synthetic VSMCs and induced BBB disruption through ECSIT-IL-6 signaling after ischemic stroke.

A Novel FLCN Intragenic Deletion Identified by NGS in a BHDS Family and Literature Review.

Birt-Hogg-Dubé syndrome (BHDS, MIM #135150), caused by germline mutations of FLCN gene, is a rare autosomal dominant inherited disorder characterized by skin fibrofolliculomas, renal cancer, pulmonary cysts and spontaneous pneumothorax. The syndrome is considered to be under-diagnosed due to variable and atypical manifestations. Herein we present a BHDS family. Targeted next generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA) revealed a novel FLCN intragenic deletion spanning exons 10-14 in four members including the proband with pulmonary cysts and spontaneous pneumothorax, one member with suspicious skin lesions and a few pulmonary cysts, as well as two asymptomatic family members. In addition, a linkage analysis further demonstrated one member with pulmonary bullae to be a BHDS-ruled-out case, whose bullae presented more likely as an aspect of paraseptal emphysema. Furthermore, the targeted NGS and MLPA data including our previous and present findings were reviewed and analyzed to compare the advantages and disadvantages of the two methods, and a brief review of the relevant literature is included. Considering the capability of the targeted NGS method to detect large intragenic deletions as well as determining deletion junctions, and the occasional false positives of MLPA, we highly recommend targeted NGS to be used for clinical molecular diagnosis in suspected BHDS patients.