GATA3 functions downstream of BRCA1 to promote DNA damage repair and suppress dedifferentiation in breast cancer.

BACKGROUND: Inadequate DNA damage repair promotes aberrant differentiation of mammary epithelial cells. Mammary luminal cell fate is mainly determined by a few transcription factors including GATA3. We previously reported that GATA3 functions downstream of BRCA1 to suppress aberrant differentiation in breast cancer. How GATA3 impacts DNA damage repair preventing aberrant cell differentiation in breast cancer remains elusive. We previously demonstrated that loss of p18, a cell cycle inhibitor, in mice induces luminal-type mammary tumors, whereas depletion of either Brca1 or Gata3 in p18 null mice leads to basal-like breast cancers (BLBCs) with activation of epithelial-mesenchymal transition (EMT). We took advantage of these mutant mice to examine the role of Gata3 as well as the interaction of Gata3 and Brca1 in DNA damage repair in mammary tumorigenesis. RESULTS: Depletion of Gata3, like that of Brca1, promoted DNA damage accumulation in breast cancer cells in vitro and in basal-like breast cancers in vivo. Reconstitution of Gata3 improved DNA damage repair in Brca1-deficient mammary tumorigenesis. Overexpression of GATA3 promoted homologous recombination (HR)-mediated DNA damage repair and restored HR efficiency of BRCA1-deficient cells. Depletion of Gata3 sensitized tumor cells to PARP inhibitor (PARPi), and reconstitution of Gata3 enhanced resistance of Brca1-deficient tumor cells to PARP inhibitor. CONCLUSIONS: These results demonstrate that Gata3 functions downstream of BRCA1 to promote DNA damage repair and suppress dedifferentiation in mammary tumorigenesis and progression. Our findings suggest that PARP inhibitors are effective for the treatment of GATA3-deficient BLBCs.

Phosphine-Capped Effects Enable Full-Color Clusteroluminescence in Nonconjugated Polyesters.

Full-color luminophores have advanced applications in materials and engineering, but constructing color-tunable clusteroluminescence (CL) from nonconjugated polymers based on through-space interactions remains a huge challenge. Herein, we develop phosphine-capped nonconjugated polyesters exhibiting blue-to-red CL (400-700 nm) based on phosphine-initiated copolymerization of epoxides and cyclic anhydrides, especially P1-0.5TPP, which exhibits red CL (610 nm) with a high quantum yield of 32%. Experiments and theoretical calculations disclose that the phosphine-capped effect in polyesters brings about conformational changes and induces phosphine-ester clusters by through-space (n,π*) interactions. Moreover, CL colors and efficiencies can be easily tailored by types of phosphines, compositions and structures of polyesters, and concentration. Significantly, the role of polymer motions (group, segmental, and chain motions) on CL originating from microregions inside polyesters is revealed. Further, phosphine-capped nonconjugated polyesters are demonstrated to be nonconjugated dyes and fluorescent fibers and are also used for multicolor light-emitting diodes including white light. This work not only provides an engineering strategy based on the end-group effect to prepare full-color clusteroluminogens but also broadens the prospects for material applications.

Variations and trade-offs in leaf and culm functional traits among 77 woody bamboo species.

BACKGROUND: Woody bamboos are the only diverse large perennial grasses in mesic-wet forests and are widely distributed in the understory and canopy. The functional trait variations and trade-offs in this taxon remain unclear due to woody bamboo syndromes (represented by lignified culm of composed internodes and nodes). Here, we examined the effects of heritable legacy and occurrence site climates on functional trait variations in leaf and culm across 77 woody bamboo species in a common garden. We explored the trade-offs among leaf functional traits, the connection between leaf nitrogen (N), phosphorus (P) concentrations and functional niche traits, and the correlation of functional traits between leaves and culms. RESULTS: The Bayesian mixed models reveal that the combined effects of heritable legacy (phylogenetic distances and other evolutionary processes) and occurrence site climates accounted for 55.10-90.89% of the total variation among species for each studied trait. The standardized major axis analysis identified trade-offs among leaf functional traits in woody bamboo consistent with the global leaf economics spectrum; however, compared to non-bamboo species, the woody bamboo exhibited lower leaf mass per area but higher N, P concentrations and assimilation, dark respiration rates. The canonical correlation analysis demonstrated a positive correlation (ρ = 0.57, P-value < 0.001) between leaf N, P concentrations and morphophysiology traits. The phylogenetic principal components and trait network analyses indicated that leaf and culm traits were clustered separately, with leaf assimilation and respiration rates associated with culm ground diameter. CONCLUSION: Our study confirms the applicability of the leaf economics spectrum and the biogeochemical niche in woody bamboo taxa, improves the understanding of woody bamboo leaf and culm functional trait variations and trade-offs, and broadens the taxonomic units considered in plant functional trait studies, which contributes to our comprehensive understanding of terrestrial forest ecosystems.

Ultrathin, Mechanically Durable, and Scalable Polymer-in-Salt Solid Electrolyte for High-Rate Lithium Metal Batteries.

Polymer-in-salt solid-state electrolytes (PIS SSEs) are emerging for high room-temperature ionic conductivity and facile handling, but suffer from poor mechanical durability and large thickness. Here, Al2O3-coated PE (PE/AO) separators are proposed as robust and large-scale substrates to trim the thickness of PIS SSEs without compromising mechanical durability. Various characterizations unravel that introducing Al2O3 coating on PE separators efficiently improves the wettability, thermal stability, and Li-dendrite resistance of PIS SSEs. The resulting PE/AO@PIS demonstrates ultra-small thickness (25 µm), exceptional mechanical durability (55.1 MPa), high decomposition temperature (330 °C), and favorable ionic conductivity (0.12 mS cm-1 at 25 °C). Consequently, the symmetrical Li cells remain stable at 0.1 mA cm-2 for 3000 h, without Li dendrite formation. Besides, the LiFePO4|Li full cells showcase excellent rate capability (131.0 mAh g-1 at 10C) and cyclability (93.6% capacity retention at 2C after 400 cycles), and high-mass-loading performance (7.5 mg cm-2). Moreover, the PE/AO@PIS can also pair with nickel-rich layered oxides (NCM811 and NCM9055), showing a remarkable specific capacity of 165.3 and 175.4 mAh g-1 at 0.2C after 100 cycles, respectively. This work presents an effective large-scale preparation approach for mechanically durable and ultrathin PIS SSEs, driving their practical applications for next-generation solid-state Li-metal batteries.

Ex vivo culture resting time impacts transplantation outcomes of genome-edited human hematopoietic stem and progenitor cells in xenograft mouse models.

Ex vivo resting culture is a standard procedure following genome editing in hematopoietic stem and progenitor cells (HSPCs). However, prolonged culture may critically affect cell viability and stem cell function. We investigated whether varying durations of culture resting times impact the engraftment efficiency of human CD34+ HSPCs edited at the BCL11A enhancer, a key regulator in the expression of fetal hemoglobin. We employed electroporation to introduce CRISPR-Cas9 components for BCL11A enhancer editing and compared outcomes with nonelectroporated (NEP) and electroporated-only (EP) control groups. Post-electroporation, we monitored cell viability, death rates, and the frequency of enriched hematopoietic stem cell (HSC) fractions (CD34+CD90+CD45RA- cells) over a 48-hour period. Our findings reveal that while the NEP group showed an increase in cell numbers 24 hours post-electroporation, both EP and BCL11A-edited groups experienced significant cell loss. Although CD34+ cell frequency remained high in all groups for up to 48 hours post-electroporation, the frequency of the HSC-enriched fraction was significantly lower in the EP and edited groups compared to the NEP group. In NBSGW xenograft mouse models, both conditioned with busulfan and nonconditioned, we found that immediate transplantation post-electroporation led to enhanced engraftment without compromising editing efficiency. Human glycophorin A+ (GPA+) red blood cells (RBCs) sorted from bone marrow of all BCL11A edited mice exhibited similar levels of γ-globin expression, regardless of infusion time. Our findings underscore the critical importance of optimizing the culture duration between genome editing and transplantation. Minimizing this interval may significantly enhance engraftment success and minimize cell loss without compromising editing efficiency. These insights offer a pathway to improve the success rates of genome editing in HSPCs, particularly for conditions like sickle cell disease.

Realization of Gapped and Ungapped Photonic Topological Anderson Insulators.

It is commonly believed that topologically nontrivial one-dimensional systems support edge states rather than bulk states at zero energy. In this work, we find an unanticipated case of topological Anderson insulator (TAI) phase where two bulk modes are degenerate at zero energy, in addition to degenerate edge modes. We term this "ungapped TAI" to distinguish it from the previously known gapped TAIs. Our experimental realization of both gapped and ungapped TAIs relies on coupled photonic resonators, in which the disorder in coupling is judiciously engineered by adjusting the spacing between the resonators. By measuring the local density of states both in the bulk and at the edges, we demonstrate the existence of these two types of TAIs, together forming a TAI plateau in the phase diagram. Our experimental findings are well supported by theoretical analysis. In the ungapped TAI phase, we observe stable coexistence of topological edge states and localized bulk states at zero energy, highlighting the distinction between TAIs and traditional topological insulators.

Asymmetric Synthesis of Tertiary α-Hydroxylation-Cyclopentanones via Synergetic Catalysis of Chiral-at-Metal Rhodium(III) Complexes/Pyrrolidine.

Catalytic and asymmetric domino Michael/aldol reaction of 1,2-dicarbonyl compounds with α,ß-unsaturated ketones under the synergetic catalysis of chiral-at-metal rhodium complexes and pyrrolidine to deliver tertiary α-hydroxylation-cyclopentanones (45-89% yields with 81-99% ee and up to >20:1 dr) bearing three contiguous stereogenic centers had been established. Moreover, the scalability and practical utility of this protocol were well demonstrated by employing a gram-scale reaction and some representative transformations.

Latent membrane protein 1 and macrophage-derived TNFα synergistically activate and mobilize invadopodia to drive invasion of nasopharyngeal carcinoma.

Invadopodia are actin-rich membrane protrusions that digest the matrix barrier during cancer metastasis. Since the discovery of invadopodia, they have been visualized as localized and dot-like structures in different types of cancer cells on top of a 2D matrix. In this investigation of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC), a highly invasive cancer frequently accompanied by neck lymph node and distal organ metastases, we revealed a new form of invadopodium with mobilizing features. Integration of live-cell imaging and molecular assays revealed the interaction of macrophage-released TNFα and EBV-encoded latent membrane protein 1 (LMP1) in co-activating the EGFR/Src/ERK/cortactin and Cdc42/N-WASP signaling axes for mobilizing the invadopodia with lateral movements. This phenomenon endows the invadopodia with massive degradative power, visualized as a shift of focal dot-like digestion patterns on a 2D gelatin to a dendrite-like digestion pattern. Notably, single stimulation of either LMP1 or TNFα could only enhance the number of ordinary dot-like invadopodia, suggesting that the EBV infection sensitizes the NPC cells to form mobilizing invadopodia when encountering a TNFα-rich tumor microenvironment. This study unveils the interplay of EBV and stromal components in driving the invasive potential of NPC via unleashing the propulsion of invadopodia in overcoming matrix hurdles. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Clinical trial recommendations using Semantics-Based inductive inference and knowledge graph embeddings.

OBJECTIVE: Designing a new clinical trial entails many decisions, such as defining a cohort and setting the study objectives to name a few, and therefore can benefit from recommendations based on exhaustive mining of past clinical trial records. This study proposes an approach based on knowledge graph embeddings and semantics-driven inductive inference for generating such recommendations. METHOD: The proposed recommendation methodology is based on neural embeddings trained on first-of-its-kind knowledge graph constructed from clinical trials data. The methodology includes design of a knowledge graph for clinical trial data, evaluation of various knowledge graph embedding techniques for it, application of a novel inductive inference method using these embeddings, and generation of recommendations for clinical trial design. The study uses freely available data from clinicaltrials.gov and related sources. RESULTS: The proposed approach for recommendations obtained relevance scores ranging from 70% to 83%. These scores were determined by evaluating the text similarity of recommended elements to actual elements used in clinical trials that are in progress. Furthermore, the most pertinent recommendations were consistently located towards the top of the list, indicating the effectiveness of our method. CONCLUSION: Our study suggests that inductive inference using node semantics is a viable approach for generating recommendations using graphs neural embeddings, and that there is a potential for improvement in training graph embeddings using node semantics.

The clinical characteristics of 1894 cases of upper respiratory papillomatosis: A single-center retrospective analysis.

BACKGROUND: With advancements in medicine and economy, it would be expected that there will be changes in the clinical characteristics of upper respiratory papillomatosis. The aim of this study was to examine the current clinical characteristics of upper respiratory papillomatosis, as there are no recent data in the literature. METHODS: The medical records of 1894 patients with upper respiratory papillomatosis were retrospectively reviewed. Data extracted included clinical features, laryngoscopy images, and surgical procedure data. RESULTS: The upper frequency of upper respiratory papillomatosis in the oropharynx was 69.1 %, and in the larynx was held 28.9 %. The overall postoperative relapse rate was 2.4 %. The relapse rate of laryngeal papillomatosis was 6.5 %. Approximately 2.6 % of cases were in children. All postoperative recurrences in children were laryngeal, and the recurrence rate was 30.4 %. CONCLUSION: The oropharynx has the highest frequency of upper respiratory papillomatosis. The larynx, however, has the highest rate of postoperative recurrence. Compared to adults, children are more likely to experience a postoperative recurrence.

Near-Infrared Emission Beyond 900†nm from Stable Radicals in Nonconjugated Poly(diphenylmethane).

Organic radicals with narrow energy gaps are highly sought-after for the production of near-infrared (NIR) fluorophores. However, the current repertoire of developed organic radicals is notably limited, facing challenges related to stability and low fluorescence efficiency. This study addresses these limitations by achieving stable radicals in nonconjugated poly(diphenylmethane) (PDPM). Notably, PDPM exhibits a well-balanced structural flexibility and rigidity, resulting in a robust intra-/inter-chain through-space conjugation (TSC). The stable radicals within PDPM, coupled with strong TSC, yield a remarkable full-spectrum emission spanning from blue to NIR beyond 900 nm. This extensive tunability is achieved through careful adjustments of concentration and excitation wavelength. The findings highlight the efficacy of polymerization in stabilizing radicals and introduce a novel approach for developing nonconjugated NIR emitters based on triphenylmethane subunits.

Regulation of PKD2 channel function by TACAN.

Autosomal dominant polycystic kidney disease is caused by mutations in the membrane receptor PKD1 or the cation channel PKD2. TACAN (also termed TMEM120A), recently reported as an ion channel in neurons for mechanosensing and pain sensing, is also distributed in diverse non-neuronal tissues, such as kidney, heart and intestine, suggesting its involvement in other functions. In this study, we found that TACAN is in a complex with PKD2 in native renal cell lines. Using the two-electrode voltage clamp in Xenopus oocytes, we found that TACAN inhibits the channel activity of PKD2 gain-of-function mutant F604P. TACAN fragments containing the first and last transmembrane domains interacted with the PKD2 C- and N-terminal fragments, respectively. The TACAN N-terminus acted as a blocking peptide, and TACAN inhibited the function of PKD2 by the binding of PKD2 with TACAN. By patch clamping in mammalian cells, we found that TACAN inhibits both the single-channel conductance and the open probability of PKD2 and mutant F604P. PKD2 co-expressed with TACAN, but not PKD2 alone, exhibited pressure sensitivity. Furthermore, we found that TACAN aggravates PKD2-dependent tail curvature and pronephric cysts in larval zebrafish. In summary, this study revealed that TACAN acts as a PKD2 inhibitor and mediates mechanosensitivity of the PKD2-TACAN channel complex. KEY POINTS: TACAN inhibits the function of PKD2 in vitro and in vivo. TACAN N-terminal S1-containing fragment T160X interacts with the PKD2 C-terminal fragment N580-L700, and its C-terminal S6-containing fragment L296-D343 interacts with the PKD2 N-terminal A594X. TACAN inhibits the function of the PKD2 channel by physical interaction. The complex of PKD2 with TACAN, but not PKD2 alone, confers mechanosensitivity.

CRISPR/Cas9-mediated simultaneous mutation of three salicylic acid 5-hydroxylase (OsS5H) genes confers broad-spectrum disease resistance in rice.

Salicylic acid (SA) is an essential plant hormone that plays critical roles in basal defence and amplification of local immune responses and establishes resistance against various pathogens. However, the comprehensive knowledge of the salicylic acid 5-hydroxylase (S5H) in rice-pathogen interaction is still elusive. Here, we reported that three OsS5H homologues displayed salicylic acid 5-hydroxylase activity, converting SA into 2,5-dihydroxybenzoic acid (2,5-DHBA). OsS5H1, OsS5H2, and OsS5H3 were preferentially expressed in rice leaves at heading stage and responded quickly to exogenous SA treatment. We found that bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo) strongly induced the expression of OsS5H1, OsS5H2, and OsS5H3. Rice plants overexpressing OsS5H1, OsS5H2, and OsS5H3 showed significantly decreased SA contents and increased 2,5-DHBA levels, and were more susceptible to bacterial blight and rice blast. A simple single guide RNA (sgRNA) was designed to create oss5h1oss5h2oss5h3 triple mutants through CRISPR/Cas9-mediated gene mutagenesis. The oss5h1oss5h2oss5h3 exhibited stronger resistance to Xoo than single oss5h mutants. And oss5h1oss5h2oss5h3 plants displayed enhanced rice blast resistance. The conferred pathogen resistance in oss5h1oss5h2oss5h3 was attributed to the significantly upregulation of OsWRKY45 and pathogenesis-related (PR) genes. Besides, flg22-induced reactive oxygen species (ROS) burst was enhanced in oss5h1oss5h2oss5h3. Collectively, our study provides a fast and effective approach to generate rice varieties with broad-spectrum disease resistance through OsS5H gene editing.

SEMI-ROLLED LEAF 10 stabilizes catalase isozyme B to regulate leaf morphology and thermotolerance in rice (Oryza sativa L.).

Plant architecture and stress tolerance play important roles in rice breeding. Specific leaf morphologies and ideal plant architecture can effectively improve both abiotic stress resistance and rice grain yield. However, the mechanism by which plants simultaneously regulate leaf morphogenesis and stress resistance remains elusive. Here, we report that SRL10, which encodes a double-stranded RNA-binding protein, regulates leaf morphology and thermotolerance in rice through alteration of microRNA biogenesis. The srl10 mutant had a semi-rolled leaf phenotype and elevated sensitivity to high temperature. SRL10 directly interacted with catalase isozyme B (CATB), and the two proteins mutually increased one other's stability to enhance hydrogen peroxide (H2 O2 ) scavenging, thereby contributing to thermotolerance. The natural Hap3 (AGC) type of SRL10 allele was found to be present in the majority of aus rice accessions, and was identified as a thermotolerant allele under high temperature stress in both the field and the growth chamber. Moreover, the seed-setting rate was 3.19 times higher and grain yield per plant was 1.68 times higher in near-isogenic line (NIL) carrying Hap3 allele compared to plants carrying Hap1 allele under heat stress. Collectively, these results reveal a new locus of interest and define a novel SRL10-CATB based regulatory mechanism for developing cultivars with high temperature tolerance and stable yield. Furthermore, our findings provide a theoretical basis for simultaneous breeding for plant architecture and stress resistance.

Exact New Mobility Edges between Critical and Localized States.

The disorder systems host three types of fundamental quantum states, known as the extended, localized, and critical states, of which the critical states remain being much less explored. Here we propose a class of exactly solvable models which host a novel type of exact mobility edges (MEs) separating localized states from robust critical states, and propose experimental realization. Here the robustness refers to the stability against both single-particle perturbation and interactions in the few-body regime. The exactly solvable one-dimensional models are featured by a quasiperiodic mosaic type of both hopping terms and on-site potentials. The analytic results enable us to unambiguously obtain the critical states which otherwise require arduous numerical verification including the careful finite size scalings. The critical states and new MEs are shown to be robust, illustrating a generic mechanism unveiled here that the critical states are protected by zeros of quasiperiodic hopping terms in the thermodynamic limit. Further, we propose a novel experimental scheme to realize the exactly solvable model and the new MEs in an incommensurate Rydberg Raman superarray. This Letter may pave a way to precisely explore the critical states and new ME physics with experimental feasibility.

Tuning Anomalous Floquet Topological Bands with Ultracold Atoms.

The Floquet engineering opens the way to create new topological states without counterparts in static systems. Here, we report the experimental realization and characterization of new anomalous topological states with high-precision Floquet engineering for ultracold atoms trapped in a shaking optical Raman lattice. The Floquet band topology is manipulated by tuning the driving-induced band crossings referred to as band inversion surfaces (BISs), whose configurations fully characterize the topology of the underlying states. We uncover various exotic anomalous topological states by measuring the configurations of BISs that correspond to the bulk Floquet topology. In particular, we identify an unprecedented anomalous Floquet valley-Hall state that possesses anomalous helical-like edge modes protected by valleys and a chiral state with high Chern number.

Berry Curvature and Bulk-Boundary Correspondence from Transport Measurement for Photonic Chern Bands.

Berry curvature is a fundamental element to characterize topological quantum physics, while a full measurement of Berry curvature in momentum space was not reported for topological states. Here we achieve two-dimensional Berry curvature reconstruction in a photonic quantum anomalous Hall system via Hall transport measurement of a momentum-resolved wave packet. Integrating measured Berry curvature over the two-dimensional Brillouin zone, we obtain Chern numbers corresponding to -1 and 0. Further, we identify bulk-boundary correspondence by measuring topology-linked chiral edge states at the boundary. The full topological characterization of photonic Chern bands from Berry curvature, Chern number, and edge transport measurements enables our photonic system to serve as a versatile platform for further in-depth study of novel topological physics.

Nomogram incorporating Epstein-Barr virus DNA and a novel immune-nutritional marker for survival prediction in nasopharyngeal carcinoma.

BACKGROUND: Since Immune response, nutritional status and Epstein-Barr Virus (EBV) DNA status have been confirmed to be relevant to the prognosis of patients with nasopharyngeal carcinoma (NPC), we believe that the combination of these factors is of great value for improving the predictive ability. LA (lymphocytes × albumin), a novel indicator, had not been studied yet in NPC. We combined it with EBV DNA and used nomograms to increase the accuracy of prognosis. METHODS: A total of 688 NPC patients were retrospectively reviewed and further divided into training and validation cohort randomly. Kaplan-Meier analyses were used to to distinguish the different survival outcomes. Multivariate Cox analyses were used to identify the independent prognostic factors for progression-free survival (PFS) and overall survival (OS). Calibration curves, concordance indexes (C-indexes) and decision curve analyses (DCA) were used to evaluate the nomograms' predictive value. RESULTS: Patients with low LA and positive EBV DNA correlated with poorer 5-year PFS and OS (all P < 0.005). In multivariate Cox analyses, LA and EBV DNA were both confirmed to be independent prognostic factors for PFS and OS (all P < 0.05). Prognostic nomograms incorporating LA and EBV DNA achieved ideal C-indexes of 0.69 (95% CI: 0.65-0.73) and 0.77 (95% CI: 0.71-0.82) in the prediction of PFS and OS. Otherwise, the calibration curves and DCA curves also revealed that our nomograms had pleasant predictive power. CONCLUSIONS: LA is a novel and powerful biomarker for predicting clinical outcomes in NPC. Our nomograms based on LA and EBV DNA can predict individual prognosis more accurately and effectively.

Impact of sex on treatment-related adverse effects and prognosis in nasopharyngeal carcinoma.

BACKGROUND: In nasopharyngeal cancer (NPC), women have a lower incidence and mortality rate than men. Whether sex influences the prognosis of NPC patients remains debatable. We retrospectively examined the influence of sex on treatment-related side effects and prognosis in NPC. METHODS: Clinical data of 1,462 patients with NPC treated at the Southern Hospital of Southern Medical University from January 2004 to December 2015 were retrospectively examined. Statistical analysis was performed to assess differences in overall survival (OS), distant metastasis-free survival (DMFS), local recurrence-free survival(LRFS), and progression-free survival(PFS), as well as treatment-related adverse effects, including myelosuppression, gastrointestinal responses, and radiation pharyngitis and dermatitis, between men and women. RESULTS: Women had better 5-year OS (81.5% vs. 87.1%, P = 0.032) and DMFS (76.2% vs. 83.9%, P = 0.004) than men. Analysis by age showed that the prognoses of premenopausal and menopausal women were better than those of men, whereas prognoses of postmenopausal women and men were not significantly different. Additionally, women had a better prognosis when stratified by treatment regimen. Furthermore, chemotherapy-related adverse effects were more severe in women than in men; however, the incidences of radiation laryngitis and dermatitis were not significantly different between the sexes. Logistic regression analysis revealed that the female sex was an independent risk factor for severe myelosuppression and gastrointestinal reactions. CONCLUSIONS: Chemotherapy-related side effects are more severe but the overall prognosis is better in women with NPC than in men with NPC. Patients may benefit from a personalized treatment approach for NPC. TRIAL REGISTRATION: This study was approved by the Medical Ethics Committee of Nanfang Hospital of the Southern Medical University (NFEC-201,710-K3).

Organophosphine as an Alkyl Transfer Shuttle for the Direct ß-Alkylation of Chalcones Using Alkyl Halides.

We report an efficient alkyl transfer strategy for the direct ß-alkylation of chalcones using commercially available alkyl bromides as alkyl reagents. In this transformation, the ortho-phosphanyl substituent in the chalcones is crucial for controlling their reactivity and selectivity. It also serves as a reliable alkyl transfer shuttle to transform electrophilic alkyl bromides into nucleophilic alkyl species in the form of quaternary phosphonium salts and transfer the alkyl group effectively to the ß-position of the chalcones. This alkyl transfer strategy can be further extended to the alkenylation of ortho-phosphanyl benzaldehydes to assemble functionalized polyenes.