Bevel-edge epitaxy of ferroelectric rhombohedral boron nitride single crystal.

Within the family of two-dimensional dielectrics, rhombohedral boron nitride (rBN) is considerably promising owing to having not only the superior properties of hexagonal boron nitride1-4-including low permittivity and dissipation, strong electrical insulation, good chemical stability, high thermal conductivity and atomic flatness without dangling bonds-but also useful optical nonlinearity and interfacial ferroelectricity originating from the broken in-plane and out-of-plane centrosymmetry5-23. However, the preparation of large-sized single-crystal rBN layers remains a challenge24-26, owing to the requisite unprecedented growth controls to coordinate the lattice orientation of each layer and the sliding vector of every interface. Here we report a facile methodology using bevel-edge epitaxy to prepare centimetre-sized single-crystal rBN layers with exact interlayer ABC stacking on a vicinal nickel surface. We realized successful accurate fabrication over a single-crystal nickel substrate with bunched step edges of the terrace facet (100) at the bevel facet (110), which simultaneously guided the consistent boron-nitrogen bond orientation in each BN layer and the rhombohedral stacking of BN layers via nucleation near each bevel facet. The pure rhombohedral phase of the as-grown BN layers was verified, and consequently showed robust, homogeneous and switchable ferroelectricity with a high Curie temperature. Our work provides an effective route for accurate stacking-controlled growth of single-crystal two-dimensional layers and presents a foundation for applicable multifunctional devices based on stacked two-dimensional materials.

NLR surveillance of pathogen interference with hormone receptors induces immunity.

Phytohormone signalling pathways have an important role in defence against pathogens mediated by cell-surface pattern recognition receptors and intracellular nucleotide-binding leucine-rich repeat class immune receptors1,2 (NLR). Pathogens have evolved counter-defence strategies to manipulate phytohormone signalling pathways to dampen immunity and promote virulence3. However, little is known about the surveillance of pathogen interference of phytohormone signalling by the plant innate immune system. The pepper (Capsicum chinense) NLR Tsw, which recognizes the effector nonstructural protein NSs encoded by tomato spotted wilt orthotospovirus (TSWV), contains an unusually large leucine-rich repeat (LRR) domain. Structural modelling predicts similarity between the LRR domain of Tsw and those of the jasmonic acid receptor COI1, the auxin receptor TIR1 and the strigolactone receptor partner MAX2. This suggested that NSs could directly target hormone receptor signalling to promote infection, and that Tsw has evolved a LRR resembling those of phytohormone receptors LRR to induce immunity. Here we show that NSs associates with COI1, TIR1 and MAX2 through a common repressor-TCP21-which interacts directly with these phytohormone receptors. NSs enhances the interaction of COI1, TIR1 or MAX2 with TCP21 and blocks the degradation of corresponding transcriptional repressors to disable phytohormone-mediated host immunity to the virus. Tsw also interacts directly with TCP21 and this interaction is enhanced by viral NSs. Downregulation of TCP21 compromised Tsw-mediated defence against TSWV. Together, our findings reveal that a pathogen effector targets TCP21 to inhibit phytohormone receptor function, promoting virulence, and a plant NLR protein has evolved to recognize this interference as a counter-virulence strategy, thereby activating immunity.

NLRs derepress MED10b- and MED7-mediated repression of jasmonate-dependent transcription to activate immunity.

Plant intracellular nucleotide-binding domain, leucine-rich repeat-containing receptors (NLRs) activate a robust immune response upon detection of pathogen effectors. How NLRs induce downstream immune defense genes remains poorly understood. The Mediator complex plays a central role in transducing signals from gene-specific transcription factors to the transcription machinery for gene transcription/activation. In this study, we demonstrate that MED10b and MED7 of the Mediator complex mediate jasmonate-dependent transcription repression, and coiled-coil NLRs (CNLs) in Solanaceae modulate MED10b/MED7 to activate immunity. Using the tomato CNL Sw-5b, which confers resistance to tospovirus, as a model, we found that the CC domain of Sw-5b directly interacts with MED10b. Knockout/down of MED10b and other subunits including MED7 of the middle module of Mediator activates plant defense against tospovirus. MED10b was found to directly interact with MED7, and MED7 directly interacts with JAZ proteins, which function as transcriptional repressors of jasmonic acid (JA) signaling. MED10b-MED7-JAZ together can strongly repress the expression of JA-responsive genes. The activated Sw-5b CC interferes with the interaction between MED10b and MED7, leading to the activation of JA-dependent defense signaling against tospovirus. Furthermore, we found that CC domains of various other CNLs including helper NLR NRCs from Solanaceae modulate MED10b/MED7 to activate defense against different pathogens. Together, our findings reveal that MED10b/MED7 serve as a previously unknown repressor of jasmonate-dependent transcription repression and are modulated by diverse CNLs in Solanaceae to activate the JA-specific defense pathways.

UBC9-mediated SUMOylation of Lamin B1 enhances DNA-damage-induced nuclear DNA leakage and autophagy after spinal cord injury.

Recent studies have shown that nucleophagy can mitigate DNA damage by selectively degrading nuclear components protruding from the nucleus. However, little is known about the role of nucleophagy in neurons after spinal cord injury (SCI). Western blot analysis and immunofluorescence were performed to evaluate the nucleophagy after nuclear DNA damage and leakage in SCI neurons in vivo and NSC34 expression in primary neurons cultured with oxygen-glucose deprivation (OGD) in vitro, as well as the interaction and colocalization of autophagy protein LC3 with nuclear lamina protein Lamin B1. The effect of UBC9, a Small ubiquitin-related modifier (SUMO) E2 ligase, on Lamin B1 SUMOylation and nucleophagy was examined by siRNA transfection or 2-D08 (a small-molecule inhibitor of UBC9), immunoprecipitation, and immunofluorescence. In SCI and OGD injured NSC34 or primary cultured neurons, neuronal nuclear DNA damage induced the SUMOylation of Lamin B1, which was required by the nuclear Lamina accumulation of UBC9. Furthermore, LC3/Atg8, an autophagy-related protein, directly bound to SUMOylated Lamin B1, and delivered Lamin B1 to the lysosome. Knockdown or suppression of UBC9 with siRNA or 2-D08 inhibited SUMOylation of Lamin B1 and subsequent nucleophagy and protected against neuronal death. Upon neuronal DNA damage and leakage after SCI, SUMOylation of Lamin B1 is induced by nuclear Lamina accumulation of UBC9. Furthermore, it promotes LC3-Lamin B1 interaction to trigger nucleophagy that protects against neuronal DNA damage.

Axially Chiral Nonbenzenoid Nanographene with Second Harmonic Generation Property.

Chiral nanographenes (NGs) have garnered significant interest as optoelectronic materials in recent years. While helically chiral NGs have been extensively studied, axially chiral NGs have only witnessed limited examples, with no prior reports of axially chiral nonbenzenoid NGs. Herein we report an axially chiral nonbenzenoid nanographene featuring six pentagons and four heptagons. This compound, denoted as 2, was efficiently synthesized via an efficient Pd-catalyzed aryl silane homocoupling reaction. The presence of two bulky 3,5-di-tert-butylphenyl groups around the axis connecting the two nonbenzenoid PAH (AHR) segments endows 2 with atropisomeric chirality and high racemization energy barrier, effectively preventing racemization of both R- and S-enantiomers at room temperature. Optically pure R-2 and S-2 were obtained by chiral HPLC separation, and they exhibit circular dichroism (CD) activity at wavelengths up to 660 nm, one of the longest wavelengths with CD responses reported for the chiral NGs. Interestingly, racemic 2 forms a homoconfiguration π-dimer in the crystal lattice, belonging to the I222 chiral space group. Consequently, this unique structure renders crystals of 2 with a second harmonic generation (SHG) response, distinguishing it from all the reported axially chiral benzenoid NGs. Moreover, R-2 and S-2 also exhibit SHG-CD properties.

Interception of Transient Allyl Radicals with Low-Valent Allylpalladium Chemistry: Tandem Pd(0/II/I)-Pd(0/II/I/II) Cycles in Photoredox/Pd Dual-Catalytic Enantioselective C(sp3)-C(sp3) Homocoupling.

We present comprehensive computational and experimental studies on the mechanism of an asymmetric photoredox/Pd dual-catalytic reductive C(sp3)-C(sp3) homocoupling of allylic electrophiles. In stark contrast to the canonical assumption that photoredox promotes bond formation via facile reductive elimination from high-valent metal-organic species, our computational analysis revealed an intriguing low-valent allylpalladium pathway that features tandem operation of Pd(0/II/I)-Pd(0/II/I/II) cycles. Specifically, we propose that (i) the photoredox/Pd system enables the in situ generation of allyl radicals from low-valent Pd(I)-allyl species, and (ii) effective interception of the fleeting allyl radical by the chiral Pd(I)-allyl species results in the formation of an enantioenriched product. Notably, the cooperation of the two pathways highlights the bifunctional role of Pd(I)-allyl species in the generation and interception of transient allyl radicals. Moreover, the mechanism implies divergent substrate-activation modes in this homocoupling reaction, suggesting a theoretical possibility for cross-coupling. Combined, the current study offers a novel mechanistic hypothesis for photoredox/Pd dual catalysis and highlights the use of low-valent allylpalladium as a means to efficiently intercept radicals for selective asymmetric bond constructions.

A study of ruxolitinib response-based stratified treatment for pediatric hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a lethal disorder characterized by hyperinflammation. Recently, ruxolitinib (RUX), targeting key cytokines in HLH, has shown promise for HLH treatment. However, there is a lack of robust clinical trials evaluating its efficacy, especially its utility as a frontline therapy. In this study (www.chictr.org.cn, ChiCTR2000031702), we designed ruxolitinib as a first-line agent for pediatric HLH and stratified the treatment based on its early response. Fifty-two newly diagnosed patients were enrolled. The overall response rate (ORR) of ruxolitinib monotherapy (day 28) was 69.2% (36/52), with 42.3% (22/52) achieving sustained complete remission (CR). All responders achieved their first response to ruxolitinib within 3 days. The response to ruxolitinib was significantly associated with the underlying etiology at enrollment (P = .009). Epstein-Barr virus (EBV)-HLH patients were most sensitive to ruxolitinib, with an ORR of 87.5% (58.3% in CR). After ruxolitinib therapy, 57.7% (30/52) of the patients entered intensive therapy with additional chemotherapy. Among them, 53.3% (16/30) patients achieved CR, and 46.7% (14/30) patients dominated by chronic active EBV infection-associated HLH (CAEBV-HLH) developed refractory HLH by week 8. The median interval to additional treatment since the first ruxolitinib administration was 6 days (range, 3-25 days). Altogether, 73.1% (38/52) of the enrolled patients achieved CR after treatment overall. The 12-month overall survival (OS) for all patients was 86.4% (95% confidence interval [CI], 77.1% to 95.7%). Ruxolitinib had low toxicity and was well tolerated compared with intensive chemotherapy. Our study provides clinical evidence for ruxolitinib as a frontline agent for pediatric HLH. The efficacy was particularly exemplified with stratified regimens based on the early differential response to ruxolitinib. This study was registered in the Chinese Clinical Trials Registry Platform (http://www.chictr.org.cn/) as ChiCTR2000031702.

Open Quantum System Dynamics from Infinite Tensor Network Contraction.

Approaching the long-time dynamics of non-Markovian open quantum systems presents a challenging task if the bath is strongly coupled. Recent proposals address this problem through a representation of the so-called process tensor in terms of a tensor network. We show that for Gaussian environments highly efficient contraction to a matrix product operator (MPO) form can be achieved with infinite MPO evolution methods, leading to significant computational speed-up over existing proposals. The result structurally resembles open system evolution with carefully designed auxiliary degrees of freedom, as in hierarchical or pseudomode methods. Here, however, these degrees of freedom are generated automatically by the MPO evolution algorithm. Moreover, the semigroup form of the resulting propagator enables us to explore steady-state physics, such as phase transitions.

The plasma-soluble CSF1R level is a promising prognostic indicator for pediatric Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a rare hematologic neoplasm characterized by the clonal proliferation of Langerhans-like cells. Colony-stimulating factor 1 receptor (CSF1R) is a membrane-bound receptor that is highly expressed in LCH cells and tumor-associated macrophages. In this study, a soluble form of CSF1R protein (sCSF1R) was identified by plasma proteome profiling, and its role in evaluating LCH prognosis was explored. We prospectively measured plasma sCSF1R levels in 104 LCH patients and 10 healthy children using ELISA. Plasma sCSF1R levels were greater in LCH patients than in healthy controls (p < .001) and significantly differed among the three disease extents, with the highest level in MS RO+ LCH patients (p < .001). Accordingly, immunofluorescence showed the highest level of membrane-bound CSF1R in MS RO+ patients. Furthermore, the plasma sCSF1R concentration at diagnosis could efficiently predict the prognosis of LCH patients treated with standard first-line treatment (AUC = 0.782, p < .001). Notably, dynamic monitoring of sCSF1R levels could predict relapse early in patients receiving BRAF inhibitor treatment. In vitro drug sensitivity data showed that sCSF1R increased resistance to Ara-C in THP-1 cells expressing ectopic BRAF-V600E. Overall, the plasma sCSF1R level at diagnosis and during follow-up is of great clinical importance in pediatric LCH patients.

Cytoplasmic tail of transmembrane dscam controls antibacterial responses by regulating cell proliferation-related genes in hemocytes of Chinese mitten crab (Eriocheir sinensis).

In arthropods, the involvement of Dscam (Down syndrome cell adhesion molecule) in innate immunity has been extensively demonstrated. Its cytoplasmic tail contains multiple conserved functional sites, which indicates its involvement in different intracellular signaling pathways. In this study, we focused on the role of the cytoplasmic tail of Dscam in the Chinese mitten crab (Eriocheir sinensis) immune defense. In the group with cytoplasmic tail knockdown (the site was located on constant exons 37 and 38), 3885 differentially expressed genes (DEGs) were identified. The DEGs were enriched in small molecule binding, protein-containing complex binding, and immunity-related pathways. The expression of selected genes were validated using quantitative real-time reverse transcription PCR. We identified key Cell cycle, Janus kinase (JAK)-signal transducer, activator of transcription (STAT) and mitogen-activated protein kinase (MAPK) signaling pathway genes, the results indicated that the cytoplasmic tail of Dscam controls antibacterial responses by regulating cell proliferation-related genes in hemocytes.

PERSISTENT SUBRETINAL FLUID AFTER VITRECTOMY FOR MACULAR HOLE-ASSOCIATED RETINAL DETACHMENT.

PURPOSE: To evaluate the incidence, associated factors, and outcome of persistent subretinal fluid (SRF) after vitrectomy for macular hole-associated retinal detachment (MHRD). METHODS: A total of 158 eyes from 156 patients with MHRD who achieved macular hole closure after primary vitrectomy were included in the analysis; persistent SRF was defined as the presence of SRF for more than 1 month after first surgery. Preoperative and postoperative parameters were analyzed for their relationship with SRF development. RESULTS: Persistent SRF was observed in 19 eyes (12.0% of 158) postoperatively. Seven eyes (36.8% of 19) with persistent SRF eventually displayed complete absorption during follow-up. Univariate analysis revealed that eyes with persistent SRF were statistically associated with internal limiting membrane inverted flap, duration of symptoms, tamponade (perfluoropropane/silicone oil: 14/5 vs. 35/104, P < 0.001), and MHRD subtype (Type 1/Type 2/Type 3: 15/4/0 vs. 60/40/39, P = 0.003). In multivariate analysis, only internal limiting membrane inverted flap (odds ratio, 15.778, 95% confidence interval, 3.170-78.523; P = 0.001) was positively associated with persistent SRF. There were no significant differences in best-corrected visual acuity improvement ( P = 0.425) between the SRF involved foveal and without involved foveal groups and no significant differences between the SRF complete absorption and incomplete absorption groups. CONCLUSION: Absorption of persistent SRF may be more difficult in MHRD eyes than in ordinary rhegmatogenous retinal detachment eyes. The internal limiting membrane inverted flap in MHRD was associated with a greater likelihood of persistent SRF. The location and incomplete absorption of persistent SRF did not seem to be associated with the final visual outcome.

IFP35 family proteins promote neuroinflammation and multiple sclerosis.

Excessive activation of T cells and microglia represents a hallmark of the pathogenesis of human multiple sclerosis (MS). However, the regulatory molecules overactivating these immune cells remain to be identified. Previously, we reported that extracellular IFP35 family proteins, including IFP35 and NMI, activated macrophages as proinflammatory molecules in the periphery. Here, we investigated their functions in the process of neuroinflammation both in the central nervous system (CNS) and the periphery. Our analysis of clinical transcriptomic data showed that expression of IFP35 family proteins was up-regulated in patients with MS. Additional in vitro studies demonstrated that IFP35 and NMI were released by multiple cells. IFP35 and NMI subsequently triggered nuclear factor kappa B-dependent activation of microglia via the TLR4 pathway. Importantly, we showed that both IFP35 and NMI activated dendritic cells and promoted naïve T cell differentiation into Th1 and Th17 cells. Nmi-/- , Ifp35-/- , or administration of neutralizing antibodies against IFP35 alleviated the immune cells' infiltration and demyelination in the CNS, thus reducing the severity of experimental autoimmune encephalomyelitis. Together, our findings reveal a hitherto unknown mechanism by which IFP35 family proteins facilitate overactivation of both T cells and microglia and propose avenues to study the pathogenesis of MS.

Large Language Models and Artificial Intelligence: A Primer for Plastic Surgeons on the Demonstrated and Potential Applications, Promises, and Limitations of ChatGPT.

BACKGROUND: The rapidly evolving field of artificial intelligence (AI) holds great potential for plastic surgeons. ChatGPT, a recently released AI large language model (LLM), promises applications across many disciplines, including healthcare. OBJECTIVES: The aim of this article was to provide a primer for plastic surgeons on AI, LLM, and ChatGPT, including an analysis of current demonstrated and proposed clinical applications. METHODS: A systematic review was performed identifying medical and surgical literature on ChatGPT's proposed clinical applications. Variables assessed included applications investigated, command tasks provided, user input information, AI-emulated human skills, output validation, and reported limitations. RESULTS: The analysis included 175 articles reporting on 13 plastic surgery applications and 116 additional clinical applications, categorized by field and purpose. Thirty-four applications within plastic surgery are thus proposed, with relevance to different target audiences, including attending plastic surgeons (n = 17, 50%), trainees/educators (n = 8, 24.0%), researchers/scholars (n = 7, 21%), and patients (n = 2, 6%). The 15 identified limitations of ChatGPT were categorized by training data, algorithm, and ethical considerations. CONCLUSIONS: Widespread use of ChatGPT in plastic surgery will depend on rigorous research of proposed applications to validate performance and address limitations. This systemic review aims to guide research, development, and regulation to safely adopt AI in plastic surgery.

Complications of Aesthetic and Reconstructive Breast Implant Capsulectomy: An Analysis of 7486 Patients Using Nationwide Outcomes Data.

BACKGROUND: Despite increasing demand for breast capsular surgery to treat various benign and malignant implant-related pathologies, high-quality evidence elucidating complication profiles of capsulectomy and capsulotomy is lacking. OBJECTIVES: We provide the largest-scale analysis of associated outcomes and complications using the Tracking Operations and Outcomes for Plastic Surgeons (TOPS) database, and investigate clinical scenarios that may subject patients to increased risks for complications, most notably, extent of capsular surgery (complete vs partial), and index indication of implantation (aesthetic vs reconstructive). METHODS: An analysis of the TOPS database from 2008-2019 was performed. CPT codes were used to identify complete capsulectomy and partial capsulectomy/capsulotomy cases. Breast implant exchange procedures constituted procedural controls. RESULTS: In total, 7,486 patients (10,703 breasts) undergoing capsulectomy or capsulotomy were assessed. Relative to controls, capsulectomy (4.40% vs 5.79%; p = 0.0154), but not capsulotomy (4.40% vs 4.50%; p = 0.8876), demonstrated higher overall complication rates. Both capsulectomies (0.83% vs 0.23%; p < 0.0001) and capsulotomies (0.56% vs 0.23%; p = 0.0307) also had greater rates of seroma relative to controls. Subgroup analyses demonstrated that reconstructive patients, relative to aesthetic patients, experienced greater overall complications (6.76% vs 4.34%; p < 0.0001), and increased risks for seroma (1.06% vs 0.47%; p = 0.0016), dehiscence (0.46% vs 0.14%; p = 0.0059), surgical site infections (1.03% vs 0.23%; p < 0.0001), and implant loss (0.52% vs 0.23%; p = 0.0401). A detailed synthesis of 30-day outcomes, including all patient- and breast-specific complications, for both capsulectomy and capsulotomy, stratified according to all potential confounders, is presented herein. CONCLUSIONS: Surgeries on the breast capsule are overall safe, though complete capsulectomies and reconstructive patients were associated with significantly increased operative risks. Present findings will enhance patient selection, counselling, and informed consent.

Artificial Intelligence-Generated Social Media Content Creation and Management Strategies for Plastic Surgeons.

BACKGROUND: Social media platforms have come to represent integral components of the professional marketing and advertising strategy for plastic surgeons. Effective and consistent content development, however, remains technically demanding and time consuming, prompting most to employ, at non-negligible costs, social media marketing specialists for content planning and development. OBJECTIVES: In the present study, we aimed to investigate the ability of presently available artificial intelligence (AI) models to assist plastic surgeons in their social media content development and sharing plans. METHODS: An AI large language model was prompted on the study's objectives through a series of standardized user interactions. Social media platforms of interest, on which the AI model was prompted, included Instagram, TikTok, and X (formerly Twitter). RESULTS: A 1-year, entirely AI-generated social media plan, comprising a total of 1091 posts for the 3 aforementioned social media platforms, is presented. Themes of the AI-generated content proposed for each platform were classified in 6 categories, including patient-related, practice-related, educational, "uplifting," interactive, and promotional posts. Overall, 91 publicly recognized holidays and observant and awareness days were incorporated into the content calendars. The AI model demonstrated an ability to differentiate between the distinct formats of each of the 3 social media platforms investigated, generating unique ideas for each, and providing detailed content development and posting instructions, scripts, and post captions, leveraging features specific to each platform. CONCLUSIONS: By providing detailed and actionable social media content creation and posting plans to plastic surgeons, presently available AI models can be readily leveraged to assist in and significantly alleviate the burden associated with social media account management, content generation, and potentially patient conversion.

Utility and Comparative Performance of Current Artificial Intelligence Large Language Models as Postoperative Medical Support Chatbots in Aesthetic Surgery.

BACKGROUND: Large Language Models (LLMs) have revolutionized the way plastic surgeons and their patients may access and leverage artificial Intelligence (AI). OBJECTIVES: The present study aims to comparatively assess the performance of two current publically-available and patient-accessible LLMs in the potential application of AI as postoperative medical support chatbots in an aesthetic surgeon's practice. METHODS: Twenty-two simulated postoperative patient presentations following aesthetic breast plastic surgery were devised and expert-validated. Complications varied in their latency within the postoperative period, as well as urgency of required medical attention. In response to each patient-reported presentation, Open AI's ChatGPT and Google's Bard, in their unmodified and freely available versions, were objectively assessed for their comparative accuracy in generating an appropriate differential diagnosis, most likely diagnosis, suggested medical disposition, treatments or interventions to begin from home, and/or red flag signs/symptoms indicating deterioration. RESULTS: ChatGPT cumulatively and significantly outperformed Bard across all objective assessement metrics examined (66% vs. 55%, respectively; p < 0.05). Accuracy in generating an appropriate differential diagnosis were 61% for ChatGPT, and 57% for Bard (p = 0.45). ChatGPT asked an average of 9.2 questions on history, relative to 6.8 questions by Bard (p < 0.001), following which, accuracies of 91% vs. 68% at arriving at the most-likely diagnosis were noted, respectively (p < 0.01). Appropriate medical dispositions were suggested with an accuracy of 50% by ChatGPT, and 41% by Bard (p = 0.40); relevant home interventions/treatments with an accuracy of 59% and 55% (p = 0.94), and red flag signs/symptoms with accuracies of 79% and 54% (p < 0.01), respectively. Detailed and comparative performance breakdowns according to complication latency and urgency are presented herein. CONCLUSIONS: ChatGPT represents the superior LLM for the potential application of AI technology in postoperative medical support chatbots. Imperfect performance and limitations identified herein may guide the necessary refinement to facilitate adoption.

Catalytic Asymmetric Synthesis of Atropisomers Bearing Multiple Chiral Elements: An Emerging Field.

With the rapid development of asymmetric catalysis, the demand for the enantioselective synthesis of complex and diverse molecules with different chiral elements is increasing. Owing to the unique features of atropisomerism, the catalytic asymmetric synthesis of atropisomers has attracted a considerable interest from the chemical science community. In particular, introducing additional chiral elements, such as carbon centered chirality, heteroatomic chirality, planar chirality, and helical chirality, into atropisomers provides an opportunity to incorporate new properties into axially chiral compounds, thus expanding the potential applications of atropisomers. Thus, it is important to perform catalytic asymmetric transformations to synthesize atropisomers bearing multiple chiral elements. In spite of challenges in such transformations, in recent years, chemists have devised powerful strategies under asymmetric organocatalysis or metal catalysis, synthesizing a wide range of enantioenriched atropisomers bearing multiple chiral elements. Therefore, the catalytic asymmetric synthesis of atropisomers bearing multiple chiral elements has become an emerging field. This review summarizes the rapid progress in this field and indicates challenges, thereby promoting this field to a new horizon.

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Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder. With the emergence of disease-modifying therapies, the prognosis of SMA has significantly improved, drawing increased attention to the importance of home rehabilitation and nursing management. Long-term, standardized home rehabilitation and nursing can delay the progression of SMA, enhance the psychological well-being, and improve the quality of life of both patients and caregivers. This article provides an overview of the goals of home rehabilitation, basic functional training methods, respiratory management, and nutritional management for SMA patients, as well as psychological health issues, emphasizing the significance of obtaining appropriate home rehabilitation and support during the care process.

Efficacy of ruxolitinib for HAVCR2 mutation-associated hemophagocytic lymphohistiocytosis and panniculitis manifestations in children.

Frequent germline mutations of HAVCR2, recently identified in subcutaneous panniculitis-like T-cell lymphoma (SPTCL), are associated with an increased risk of hemophagocytic lymphohistiocytosis (HLH). However, SPTCL-HLH represents a challenge because of the difficulties in treatment with poor survival. Its malignant nature, specifically harbouring HAVCR2 mutations, has also been questioned. To better understand its pathology and treatment, we analysed the clinical data of six patients diagnosed at our centre. The median age at onset was 10.5 years (range, 0.8-12.4). Five patients presented with skin lesions of subcutaneous nodules/plaques and/or ulceration. All patients developed HLH; notably, one infant only had HLH without skin involvement. Histopathologically, only two patients were diagnosed with SPTCL and three were reported as panniculitis with no sufficient evidence of lymphoma. Genetically, germline homozygous mutation of HAVCR2 (p.Y82C) was identified in all patients, with a median diagnosis time of 4.6 months. All patients initially received corticosteroids, immunosuppressants or chemotherapy, achieving unfavourable responses. Strikingly, they responded well to ruxolitinib targeting inflammatory cytokines, allowing rapid disease resolution and/or long-term maintenance of remission. The excellent efficacy of ruxolitinib highlights this disease as an inflammatory condition instead of neoplastic nature and indicates novel agents targeting key inflammatory pathways as an encouraging approach for this disease entity.