Explainable El Niño predictability from climate mode interactions.

The El Niño-Southern Oscillation (ENSO) provides most of the global seasonal climate forecast skill1-3, yet, quantifying the sources of skilful predictions is a long-standing challenge4-7. Different sources of predictability affect ENSO evolution, leading to distinct global effects. Artificial intelligence forecasts offer promising advancements but linking their skill to specific physical processes is not yet possible8-10, limiting our understanding of the dynamics underpinning the advancements. Here we show that an extended nonlinear recharge oscillator (XRO) model shows skilful ENSO forecasts at lead times up to 16-18 months, better than global climate models and comparable to the most skilful artificial intelligence forecasts. The XRO parsimoniously incorporates the core ENSO dynamics and ENSO's seasonally modulated interactions with other modes of variability in the global oceans. The intrinsic enhancement of ENSO's long-range forecast skill is traceable to the initial conditions of other climate modes by means of their memory and interactions with ENSO and is quantifiable in terms of these modes' contributions to ENSO amplitude. Reforecasts using the XRO trained on climate model output show that reduced biases in both model ENSO dynamics and in climate mode interactions can lead to more skilful ENSO forecasts. The XRO framework's holistic treatment of ENSO's global multi-timescale interactions highlights promising targets for improving ENSO simulations and forecasts.

Auxin resistant 2 and short hypocotyl 2 regulate cotton fiber initiation and elongation.

Auxin, a pivotal regulator of diverse plant growth processes, remains central to development. The auxin-responsive genes auxin/indole-3-acetic acids (AUX/IAAs) are indispensable for auxin signal transduction, which is achieved through intricate interactions with auxin response factors (ARFs). Despite this, the potential of AUX/IAAs to govern the development of the most fundamental biological unit, the single cell, remains unclear. In this study, we harnessed cotton (Gossypium hirsutum) fiber, a classic model for plant single-cell investigation, to determine the complexities of AUX/IAAs. Our research identified 2 pivotal AUX/IAAs, auxin resistant 2 (GhAXR2) and short hypocotyl 2 (GhSHY2), which exhibit opposite control over fiber development. Notably, suppressing GhAXR2 reduced fiber elongation, while silencing GhSHY2 fostered enhanced fiber elongation. Investigating the mechanistic intricacies, we identified specific interactions between GhAXR2 and GhSHY2 with distinct ARFs. GhAXR2's interaction with GhARF6-1 and GhARF23-2 promoted fiber cell development through direct binding to the AuxRE cis-element in the constitutive triple response 1 promoter, resulting in transcriptional inhibition. In contrast, the interaction of GhSHY2 with GhARF7-1 and GhARF19-1 exerted a negative regulatory effect, inhibiting fiber cell growth by activating the transcription of xyloglucan endotransglucosylase/hydrolase 9 and cinnamate-4-hydroxylase. Thus, our study reveals the intricate regulatory networks surrounding GhAXR2 and GhSHY2, elucidating the complex interplay of multiple ARFs in AUX/IAA-mediated fiber cell growth. This work enhances our understanding of single-cell development and has potential implications for advancing plant growth strategies and agricultural enhancements.

Author Correction: El Niño-Southern Oscillation complexity.

In this Review, the middle initial of author Kim M. Cobb was omitted. The original Review has been corrected online.

Interfacial Polarization Locked Flexible ß-Phase Glycine/Nb2CTx Piezoelectric Nanofibers.

Biomolecular piezoelectric materials show great potential in the field of wearable and implantable biomedical devices. Here, a self-assemble approach is developed to fabricating flexible ß-glycine piezoelectric nanofibers with interfacial polarization locked aligned crystal domains induced by Nb2CTx nanosheets. Acted as an effective nucleating agent, Nb2CTx nanosheets can induce glycine to crystallize from edges toward flat surfaces on its 2D crystal plane and form a distinctive eutectic structure within the nanoconfined space. The interfacial polarization locking formed between O atom on glycine and Nb atom on Nb2CTx is essential to align the ß-glycine crystal domains with (001) crystal plane intensity extremely improved. This ß-phase glycine/Nb2CTx nanofibers (Gly-Nb2C-NFs) exhibit fabulous mechanical flexibility with Young's modulus of 10 MPa, and an enhanced piezoelectric coefficient of 5.0 pC N-1 or piezoelectric voltage coefficient of 129 × 10-3Vm N-1. The interface polarization locking greatly improves the thermostability of ß-glycine before melting (≈210°C). A piezoelectric sensor based on this Gly-Nb2C-NFs is used for micro-vibration sensing in vivo in mice and exhibits excellent sensing ability. This strategy provides an effective approach for the regular crystallization modulation for glycine crystals, opening a new avenue toward the design of piezoelectric biomolecular materials induced by 2D materials.

The structure of MgtE in the absence of magnesium provides new insights into channel gating.

MgtE is a Mg2+ channel conserved in organisms ranging from prokaryotes to eukaryotes, including humans, and plays an important role in Mg2+ homeostasis. The previously determined MgtE structures in the Mg2+-bound, closed-state, and structure-based functional analyses of MgtE revealed that the binding of Mg2+ ions to the MgtE cytoplasmic domain induces channel inactivation to maintain Mg2+ homeostasis. There are no structures of the transmembrane (TM) domain for MgtE in Mg2+-free conditions, and the pore-opening mechanism has thus remained unclear. Here, we determined the cryo-electron microscopy (cryo-EM) structure of the MgtE-Fab complex in the absence of Mg2+ ions. The Mg2+-free MgtE TM domain structure and its comparison with the Mg2+-bound, closed-state structure, together with functional analyses, showed the Mg2+-dependent pore opening of MgtE on the cytoplasmic side and revealed the kink motions of the TM2 and TM5 helices at the glycine residues, which are important for channel activity. Overall, our work provides structure-based mechanistic insights into the channel gating of MgtE.

Rapidly progressive necrotizing enterocolitis: Risk factors and a predictive model.

BACKGROUND: Rapidly progressive necrotizing enterocolitis (RP-NEC) is a particular subtype of NEC known for its rapid progression and high mortality rate. The objective of this study was to establish a predictive model for RP-NEC. METHODS: This was a retrospective single-center cohort study. Patients were newborn infants with NEC (Bell's stage ≥ IIB) admitted from January 1, 2016 to December 31, 2023. The primary outcome was RP-NEC defined as the need for surgical intervention and/or death within 48 hours of the onset of NEC. RESULTS: Totally 334 newborn infants were included, among which 82 (24.6%) were RP-NEC cases with a gestation age 34.1 (31.0, 37.0) weeks and birth weight 2100 (1413, 2800) g. Plasma sodium <135 mmol/L, C-reactive protein ≥10 mg/L, platelet count <100 × 109/L, lymphocyte count <1.5 × 109/L, pH <7.2 in blood gas, and ascites at NEC onset were identified as independent risk factors for RP-NEC. The model established presented an AUC value of 0.983 (95% CI 0.97-0.99). The calibration curve for validation was applied revealing a slope close to unity while the Hosmer-Lemeshow test yielded χ2 = 2.550 (p = 0.636). CONCLUSION: The predictive model established on the above 6 items of RP-NEC is highly promising. IMPACT: Currently, there is a paucity of research on this specific type of severe necrotizing enterocolitis (NEC) characterized by rapid progression. Our study was to investigate the risk factors associated with surgical intervention and/or death within 48 hours following onset in infants with NEC, establish a predictive model for infants with rapidly progressive NEC. The new data presented in this study was the ROC curve combining the above factors as well as hyponatremia.

Preparation of Indolin-3-one-Containing 1,4-Naphthoquinone Derivatives via Organocatalytic Asymmetric Michael Addition Reaction.

This article explores the asymmetric Michael addition reaction of 2-hydroxy-1,4-naphthoquinone and indole-3-ones catalyzed by cinchona alkaloids. This strategy utilizes 2-hydroxy-1,4-naphthoquinone and easily prepared indole-3-one as substrates, resulting in the synthesis of 23 unprecedented indolin-3-ones bearing a 1,4-naphthoquinone unit at the C2 position of indole under simple and mild reaction conditions, with up to 88% yield, 98% ee, and >20:1 dr.

El Niño-Southern Oscillation complexity.

El Niño events are characterized by surface warming of the tropical Pacific Ocean and weakening of equatorial trade winds that occur every few years. Such conditions are accompanied by changes in atmospheric and oceanic circulation, affecting global climate, marine and terrestrial ecosystems, fisheries and human activities. The alternation of warm El Niño and cold La Niña conditions, referred to as the El Niño-Southern Oscillation (ENSO), represents the strongest year-to-year fluctuation of the global climate system. Here we provide a synopsis of our current understanding of the spatio-temporal complexity of this important climate mode and its influence on the Earth system.

Design, synthesis, and antifungal activity of novel pyrazole carboxamide derivatives containing benzimidazole moiety as potential SDH inhibitors.

To address the urgent need for new antifungal agents, a collection of novel pyrazole carboxamide derivatives incorporating a benzimidazole group were innovatively designed, synthesized, and evaluated for their efficacy against fungal pathogens. The bioassay results revealed that the EC50 values for the compounds A7 (3-(difluoromethyl)-1-methyl-N-(1-propyl-1H-benzo[d]imidazol-2-yl)-1H-pyrazole-4-carboxamide) and B11 (N-(1-(4-chlorobenzyl)-1H-benzo[d]imidazol-2-yl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide) against B. cinerea were notably low to 0.79 µg/mL and 0.56 µg/mL, respectively, demonstrating the potency comparable to that of the control fungicide boscalid, which has an EC50 value of 0.60 µg/mL. Noteworthy is the fact that in vivo tests demonstrated that A7 and B11 showed superior protective effects on tomatoes and strawberries against B. cinerea infection when juxtaposed with the commercial fungicide carbendazim. The examination through scanning electron microscopy revealed that B11 notably alters the morphology of the fungal mycelium, inducing shrinkage and roughening of the hyphal surfaces. To elucidate the mechanism of action, the study on molecular docking and molecular dynamics simulations was conducted, which suggested that B11 effectively interacts with crucial amino acid residues within the active site of succinate dehydrogenase (SDH). This investigation contributes a novel perspective for the structural design and diversification of potential SDH inhibitors, offering a promising avenue for the development of antifungal therapeutics.

On the influence of ENSO complexity on Pan-Pacific coastal wave extremes.

Wind-generated waves are dominant drivers of coastal dynamics and vulnerability, which have considerable impacts on littoral ecosystems and socioeconomic activities. It is therefore paramount to improve coastal hazards predictions through the better understanding of connections between wave activity and climate variability. In the Pacific, the dominant climate mode is El Niño Southern Oscillation (ENSO), which has known a renaissance of scientific interest leading to great theoretical advances in the past decade. Yet studies on ENSO's coastal impacts still rely on the oversimplified picture of the canonical dipole across the Pacific. Here, we consider the full ENSO variety to delineate its essential teleconnection pathways to tropical and extratropical storminess. These robust seasonally modulated relationships allow us to develop a mathematical model of coastal wave modulation essentially driven by ENSO's complex temporal and spatial behavior. Accounting for this nonlinear climate control on Pan-Pacific wave activity leads to a much better characterization of waves' seasonal to interannual variability (+25% in explained variance) and intensity of extremes (+60% for strong ENSO events), therefore paving the way for significantly more accurate forecasts than formerly possible with the previous baseline understanding of ENSO's influence on coastal hazards.

Development of a Fluorescent Assay and Imidazole-Containing Inhibitors by Targeting SARS-CoV-2 Nsp13 Helicase.

Nsp13, a non-structural protein belonging to the coronavirus family 1B (SF1B) helicase, exhibits 5'-3' polarity-dependent DNA or RNA unwinding using NTPs. Crucially, it serves as a key component of the viral replication-transcription complex (RTC), playing an indispensable role in the coronavirus life cycle and thereby making it a promising target for broad-spectrum antiviral therapies. The imidazole scaffold, known for its antiviral potential, has been proposed as a potential scaffold. In this study, a fluorescence-based assay was designed by labeling dsDNA substrates with a commercial fluorophore and monitoring signal changes upon Nsp13 helicase activity. Optimization and high-throughput screening validated the feasibility of this approach. In accordance with the structural characteristics of ADP, we employed a structural-based design strategy to synthesize three classes of imidazole-based compounds through substitution reaction. Through in vitro activity research, pharmacokinetic parameter analysis, and molecular docking simulation, we identified compounds A16 (IC50 = 1.25 µM) and B3 (IC50 = 0.98 µM) as potential lead antiviral compounds for further targeted drug research.

A fatal case of neonatal viral sepsis caused by human parainfluenza virus type 3.

BACKGROUND: Sepsis is a systemic inflammatory response syndrome caused by severe infection in children, but cases of sepsis associated with human parainfluenza virus (HPIV) have been rarely reported in newborns. CASE PRESENTATION: We report a case of HPIV-3 positive full-term newborn admitted to the Neonatal Intensive Care Unit of Beijing Children's Hospital due to hematuria, gloomy spirit, inactivity and loss of appetite for 6 h. He had septic shock when he arrived the Accident & Emergency Department requiring immediate intubation and mechanical ventilation. Intravenous antibiotics were started. He had completely negative response to all anti-shock treatments including fluid resuscitation and vasopressor supports, and died 14 h later. Viral nucleic acid detection and metagenomic next-generation sequencing (mNGS) analyses of nasopharyngeal aspirate and blood specimens verified an HPIV-3 infection, with negative bacterial culture results. The HPIV-3 strain detected in this patient was subtyped as HPIV C3a, and two unreported amino acid mutations were found in the HN protein region. CONCLUSION: The patient had a severe infection associated with HPIV-3, which was the cause of sepsis and septic shock. This study showed the diagnostic value of mNGS in etiological diagnosis, especially in severe neonatal case.

The effect of genetic variation and mRNA expression of interleukin-17A gene on susceptibility to asthma.

Analyzing the genetic variation and mRNA expression of interleukin-17A (IL-17A) gene and its impact on asthma susceptibility was the purpose of this study. 120 asthma patients were selected as the asthma group, and another 120 healthy individuals who underwent physical examination were selected as the health group; Compare the cytokine levels and mRNA expression of IL-17A between two groups, as well as the clinical indicator total immunoglobulin E (TIgE) levels; The genotype and allele distribution frequency of IL-17A Single-nucleotide polymorphism locus rs2275913 and rs8193036 were compared between the two groups; Compare the serum IL-17A and TIgE levels of different genotypes at rs2275913 and rs8193036 loci; and logistic regression was used to evaluate the impact of IL-17A on asthma susceptibility. The serum levels of IL-17A, TIgE, and IL-17AmRNA expression in the asthma group were higher than those in the healthy group (P<0.05). There were three genotypes of AA, AG and GG at rs2275913 locus, and the frequency distribution between the two groups was significant (P<0.05), and the frequency of A Allele frequency in asthma group was higher than that in healthy group (P<0.05). There are three genotypes of CC, CT, and TT at the rs8193036 locus, and there was no significant difference in the frequency distribution between the two groups (P>0.05). There is no difference in the frequency distribution of alleles C and T between the two groups (P>0.05). The levels of IL-17A and TIgE in the rs2275913AA genotype were higher than those in the AG and GG genotypes (P<0.05); There was no difference in IL-17A and TIgE levels among different genotypes of rs8193036 (P>0.05). The rs2275913 polymorphism was associated with asthma susceptibility and is an independent risk parameter for asthma susceptibility. Upregulation of serum IL-17A and TIgE, as well as overexpression of IL-17A mRNA, were closely related to asthma susceptibility in asthma patients. The rs2275913 polymorphism had a significant role in increasing the risk of asthma, and variant allele A may be a susceptibility factor for increasing asthma risk.

Summertime stationary waves integrate tropical and extratropical impacts on tropical cyclone activity.

Tropical cyclones (TC) are one of the most severe storm systems on Earth and cause significant loss of life and property upon landfall in coastal areas. A better understanding of their variability mechanisms will help improve the TC seasonal prediction skill and mitigate the destructive impacts of the storms. Early studies focused primarily on tropical processes in regulating the variability of TC activity, while recent studies suggest also some long-range impacts of extratropical processes, such as lateral transport of dry air and potential vorticity by large-scale waves. Here we show that stationary waves in the Northern Hemisphere integrate tropical and extratropical impacts on TC activity in July through October. In particular, tropical upper-tropospheric troughs (TUTTs), as part of the summertime stationary waves, are associated with the variability of large-scale environmental conditions in the tropical North Atlantic and North Pacific and significantly correlated to the variability of TC activity in these basins. TUTTs are subject to the modulation of diabatic heating in various regions and are the preferred locations for extratropical Rossby wave breaking (RWB). A strong TUTT in a basin is associated with enhanced RWB and tropical-extratropical stirring in that basin, and the resultant changes in the tropical atmospheric conditions modulate TC activity. In addition, the anticorrelation of TUTTs between the North Atlantic and North Pacific makes the TC activity indices over the two basins compensate each other, rendering the global TC activity less variable than otherwise would be the case if TUTTs were independent.

Responses of the gut microbiota to environmental heavy metal pollution in tree sparrow (Passer montanus) nestlings.

Gut microbiota plays a critical role in regulating the health and adaptation of wildlife. However, our understanding of how exposure to environmental heavy metals influences the gut microbiota of wild birds, particularly during the vulnerable and sensitive nestling stage, remains limited. In order to investigate the relationship between heavy metals and the gut microbiota, we analyzed the characteristics of gut microbiota and heavy metals levels in tree sparrow nestlings at different ages (6, 9 and 12-day-old). The study was conducted in two distinct areas: Baiyin (BY), which is heavily contaminated with heavy metals, and Liujiaxia (LJX), a relatively unpolluted area. Our result reveled a decrease in gut microbiota diversity and increased inter-individual variation among nestlings in BY. However, we also observed an increase in the abundance of bacterial groups and an up-regulation of bacterial metabolic functions associated with resistance to heavy metals toxicity in BY. Furthermore, we identified a metal-associated shift in the relative abundance of microbial taxa in 12-day-old tree sparrow nestlings in BY, particularly involving Aeromonadaceae, Ruminococcaceae and Pseudomonadaceae. Moreover, a significant positive correlation was found between the body condition of tree sparrow nestlings and the abundance of Bifidobacteriaceae in BY. Collectively, our findings indicate that the gut microbiota of tree sparrow nestlings is susceptible to heavy metals during early development. However, the results also highlight the presence of adaptive responses that enable them to effectively cope with environmental heavy metal pollution.

A completely digital approach to fabricating multiple-unit fixed partial dentures to retrofit existing removable partial dentures in patients with fixed and removable prostheses.

Fabricating a multiple-unit fixed partial denture to retrofit an existing removable partial denture in patients with fixed and removable prostheses is challenging. The presented completely digital approach is an efficient and precise treatment that does not deprive the patient of the removable partial denture.

Clinical outcomes of EGFR-TKIs in advanced squamous cell lung cancer.

We aimed to explore the treatment efficacy of first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for lung squamous cell carcinoma (SCC) patients and identify potential beneficial subgroups of EGFR-mutated lung SCC patients in this study. Between February 1st, 2013 and December 1st, 2021, 657 advanced lung SCC patients were enrolled at Zhejiang Cancer Hospital. Amplification refractory mutation system PCR or next-generation sequencing were used to detect gene abnormality. Clinicopathological features were analyzed by chi-square test and the clinical results of lung SCC patients who received first-generation EGFR-TKI were analyzed by the Kaplan-Meier method. Lung SCC patients harboring EGFR mutation accounted for 11.0% in this study. Of 657 lung SCC patients, the median PFS and OS of 116 patients who received targeted therapy were 3.6 months and 16.2 months, patients treated with targeted therapy had similar OS to patients without targeted therapy (p=0.839). Of 110 lung SCC patients who received first-generation EGFR-TKI, EGFR-mutated patients had long PFS (p=0.000) but similar OS (p=0.472) than patients with EGFR wide type. EGFR-mutated SCC patients who received first-generation EGFR-TKI as a first-line benefit are equal to patients who received first-generation EGFR-TKI as the second line or beyond according to similar PFS (p=0.311) and OS (p=0.721) between them. In addition, there was also no significant difference in PFS (p=0.376) and OS (p=0.205) between patients with exon 19 deletion and L858R point mutation. Lung SCC patients harboring EGFR mutation received first-generation EGFR-TKI had better clinical survival than patients with EGFR wide type.

Treatment of scarring alopecia in children using follicular unit hair transplantation.

BACKGROUND: Scarring alopecia can significantly affect children emotionally. Follicular unit excision (FUE) and follicular unit transplantation (FUT) have been applied for scar treatment. OBJECTIVE: This study aimed to evaluate the safety and feasibility of follicular unit hair transplantation in treating scarring alopecia in children. PATIENTS AND METHODS: A total of nine children (seven males and two females) with cicatricial alopecia, ranging in age from 5 years, 2 months to 12 years, 10 months were included in this study. Scar formation time ranged from 7 months to 5 years. Sites were vertex (2), eyebrow (3), frontal hairline (3), and temporal regions (2). RESULTS: Nine children in this group were followed up for 6-34 months with the following treatment options: FUE (5 cases), FUT (3 cases), and FUT combined with FUE (1 case). No significant complications were observed during the treatment. The transplanted hair grew well, the direction and shape were satisfactory, and the survival rate was >90%. CONCLUSION: For children with burn trauma and cicatricial alopecia after surgery, hair transplantation can significantly improve their appearance with low surgical risk and high patient satisfaction rate.

Preparation Process Optimization and Performance Characterization of Feed Plant Essential Oil Microcapsules.

The exploration of safe antibiotic substitutes is one of the research hotspots in animal husbandry. Adding suitable plant essential oils into feed could improve the growth performance and immune capacity of animals. In order to make plant essential oil play a better role in feed application, sodium alginate and chitosan were used as the wall materials, and blended plant essential oils (BEO) as the core material to prepare BEO microcapsules by the sharp-hole condensation method. On the basis of single-factor experiments, the optimal preparation conditions for BEO microcapsules were obtained by response surface experiments. The physicochemical properties were characterized and analyzed by Fourier-transform infrared spectroscopy (FTIR) and field scanning electron microscope (FSEM). Meanwhile, the release mechanism was studied by simulating a gastrointestinal sustained-release experiment. The results showed that under the optimal preparation conditions, the encapsulation efficiency of BEO microcapsules could reach 80.33 ± 2.35%. FTIR and SEM analysis displayed that the microcapsules obtained had uniform color and size and a complete and compact structure. In vitro study indicated that the release amount of BEO microcapsules in the simulated intestinal fluid is higher than that in the simulated intestinal fluid, which was consistent with animal digestive and absorptive characteristics.

Capturing the Missing Carbon Cage Isomer of C84 via Mutual Stabilization of a Triangular Monometallic Cyanide Cluster.

Monometallic cyanide clusterfullerenes (CYCFs) represent a unique branch of endohedral clusterfullerenes with merely one metal atom encapsulated, offering a model system for elucidating structure-property correlation, while up to now only C82 and C76 cages have been isolated for the pristine CYCFs. C84 is one of the most abundant fullerenes and has 24 isomers obeying the isolated pentagon rule (IPR), among which 14 isomers have been already isolated, whereas the C2v(17)-C84 isomer has lower relative energy than several isolated isomers but never been found for empty and endohedral fullerenes. Herein, four novel C84-based pristine CYCFs with variable encapsulated metals and isomeric cages, including MCN@C2(13)-C84 (M = Y, Dy, Tb) and DyCN@C2v(17)-C84, have been synthesized and isolated, fulfilling the first identification of the missing C2v(17)-C84 isomer, which can be interconverted from the C2(13)-C84 isomer through two steps of Stone-Wales transformation. The molecular structures of these four C84-based CYCFs are determined unambiguously by single-crystal X-ray diffraction. Surprisingly, although the ionic radii of Y3+, Dy3+, and Tb3+ differ slightly by only 0.01 Å, such a subtle difference leads to an obvious change in the metal-cage interactions, as inferred from the distance between the metal atom and the nearest hexagon center of the C2(13)-C84 cage. On the other hand, upon altering the isomeric cage from DyCN@C2(13)-C84 to DyCN@C2v(17)-C84, the Dy-cage distance changes as well, indicating the interplay between the encapsulated DyCN cluster and the outer cage. Therefore, we demonstrate that the metal-cage interactions within CYCFs can be steered via both internal and external routes.