Fabrication strategies for chiral self-assembly surface.

Chiral self-assembly is the spontaneous organization of individual building blocks from chiral (bio)molecules to macroscopic objects into ordered superstructures. Chiral self-assembly is ubiquitous in nature, such as DNA and proteins, which formed the foundation of biological structures. In addition to chiral (bio) molecules, chiral ordered superstructures constructed by self-assembly have also attracted much attention. Chiral self-assembly usually refers to the process of forming chiral aggregates in an ordered arrangement under various non-covalent bonding such as H-bond, π-π interactions, van der Waals forces (dipole-dipole, electrostatic effects, etc.), and hydrophobic interactions. Chiral assembly involves the spontaneous process, which followed the minimum energy rule. It is essentially an intermolecular interaction force. Self-assembled chiral materials based on chiral recognition in electrochemistry, chiral catalysis, optical sensing, chiral separation, etc. have a broad application potential with the research development of chiral materials in recent years.

Eosinophil-mediated suppression and anti-IL-5 enhancement of plasmacytoid dendritic cell interferon responses in asthma.

BACKGROUND: Virus-induced IFN-α secretion by plasmacytoid dendritic cells (pDCs) is negatively impacted by IgE and has been linked to asthma exacerbations. Eosinophils, another contributor to type 2 inflammation, are also associated with asthma severity. OBJECTIVE: We sought to investigate the impact of eosinophils on pDC antiviral interferon responses and determine whether anti-IL-5/5Rα therapy enhances pDC antiviral function. METHODS: Blood pDCs purified from anonymous donors were stimulated in vitro with rhinovirus (RV)-16 in the presence or absence of eosinophils/eosinophil supernatants. IFN-α was measured in supernatants and RNA collected for bulk RNA-sequencing. Next, purified pDCs from 8 individuals with moderate to severe asthma, treated or not treated with anti-IL-5/5Rα therapy, were cultured ex vivo with or without RV; IFN-α secretion and differential gene expression analysis were compared between groups. RESULTS: Exposure to either eosinophils or eosinophil supernatants inhibited RV-induced pDC IFN-α secretion in a dose-dependent manner and did not impact pDC viability. Eosinophil-derived neurotoxin and TGF-ß partially recapitulated pDC IFN-α inhibition. Transcriptome analysis revealed global repression of pDC interferon response patterns by eosinophils, most notably in basal expression of interferon-stimulated genes. Increased RV-induced IFN-α secretion and transcription as well as increased basal interferon-stimulated gene expression was detected in pDCs from participants treated with anti-IL-5/5Rα therapy. CONCLUSIONS: Our findings highlight a novel mechanism through which type 2 inflammation regulates pDC IFN-α responses relevant to RV respiratory infections in the context of eosinophilic airway disease, suggesting a potential mechanism through which eosinophil-depleting therapies may reduce severity of RV illnesses.

Declining global warming effects on the phenology of spring leaf unfolding.

Earlier spring leaf unfolding is a frequently observed response of plants to climate warming. Many deciduous tree species require chilling for dormancy release, and warming-related reductions in chilling may counteract the advance of leaf unfolding in response to warming. Empirical evidence for this, however, is limited to saplings or twigs in climate-controlled chambers. Using long-term in situ observations of leaf unfolding for seven dominant European tree species at 1,245 sites, here we show that the apparent response of leaf unfolding to climate warming (ST, expressed in days advance of leaf unfolding per °C warming) has significantly decreased from 1980 to 2013 in all monitored tree species. Averaged across all species and sites, ST decreased by 40% from 4.0 ± 1.8 days °C(-1) during 1980-1994 to 2.3 ± 1.6 days °C(-1) during 1999-2013. The declining ST was also simulated by chilling-based phenology models, albeit with a weaker decline (24-30%) than observed in situ. The reduction in ST is likely to be partly attributable to reduced chilling. Nonetheless, other mechanisms may also have a role, such as 'photoperiod limitation' mechanisms that may become ultimately limiting when leaf unfolding dates occur too early in the season. Our results provide empirical evidence for a declining ST, but also suggest that the predicted strong winter warming in the future may further reduce ST and therefore result in a slowdown in the advance of tree spring phenology.

Identifying the SUMO1 modification of FAM122A leading to the degradation of PP2A-Cα by ubiquitin-proteasome system.

FAM122A is a highly conserved protein in mammals. Here, we identify that FAM122A can be sumoylated at lysine 89, which can be de-conjugated by SENP1. Furthermore, the sumoylation of FAM122A reduces the PP2A-Cα protein level together with the reduced phosphatase activity of PP2A, which suppresses cell proliferation. Collectively, our results suggest that the sumoylation of FAM122A may have a significant role in cellular function.

Increased heat requirement for leaf flushing in temperate woody species over 1980-2012: effects of chilling, precipitation and insolation.

Recent studies have revealed large unexplained variation in heat requirement-based phenology models, resulting in large uncertainty when predicting ecosystem carbon and water balance responses to climate variability. Improving our understanding of the heat requirement for spring phenology is thus urgently needed. In this study, we estimated the species-specific heat requirement for leaf flushing of 13 temperate woody species using long-term phenological observations from Europe and North America. The species were defined as early and late flushing species according to the mean date of leaf flushing across all sites. Partial correlation analyses were applied to determine the temporal correlations between heat requirement and chilling accumulation, precipitation and insolation sum during dormancy. We found that the heat requirement for leaf flushing increased by almost 50% over the study period 1980-2012, with an average of 30 heat units per decade. This temporal increase in heat requirement was observed in all species, but was much larger for late than for early flushing species. Consistent with previous studies, we found that the heat requirement negatively correlates with chilling accumulation. Interestingly, after removing the variation induced by chilling accumulation, a predominantly positive partial correlation exists between heat requirement and precipitation sum, and a predominantly negative correlation between heat requirement and insolation sum. This suggests that besides the well-known effect of chilling, the heat requirement for leaf flushing is also influenced by precipitation and insolation sum during dormancy. However, we hypothesize that the observed precipitation and insolation effects might be artefacts attributable to the inappropriate use of air temperature in the heat requirement quantification. Rather than air temperature, meristem temperature is probably the prominent driver of the leaf flushing process, but these data are not available. Further experimental research is thus needed to verify whether insolation and precipitation sums directly affect the heat requirement for leaf flushing.

Unexpected role of winter precipitation in determining heat requirement for spring vegetation green-up at northern middle and high latitudes.

Heat requirement, expressed in growing degree days (GDD), is a widely used method to assess and predict the effect of temperature on plant development. Until recently, the analysis of spatial patterns of GDD requirement for spring vegetation green-up onset was limited to local and regional scales, mainly because of the sparse and aggregated spatial availability of ground phenology data. Taking advantage of the large temporal and spatial scales of remote sensing-based green-up onset data, we studied the spatial patterns of GDD requirement for vegetation green-up at northern middle and high latitudes. We further explored the correlations between GDD requirement for vegetation green-up and previous winter season chilling temperatures and precipitation, using spatial partial correlations. We showed that GDD requirement for vegetation green-up onset declines towards the north at a mean rate of 18.8 °C-days per degree latitude between 35°N and 70°N, and vary significantly among different vegetation types. Our results confirmed that the GDD requirement for vegetation green-up is negatively correlated with previous winter chilling, which was defined as the number of chilling days from the day when the land surface froze in the previous autumn to the day of green-up onset. This negative correlation is a well-known phenomenon from local studies. Interestingly, irrespective of the vegetation type, we also found a positive correlation between the GDD requirement and previous winter season precipitation, which was defined as the sum of the precipitation of the month when green-up onset occur and the precipitation that occurred during the previous 2 months. Our study suggests that GDD requirement, chilling and precipitation may have complex interactions in their effects on spring vegetation green-up phenology. These findings have important implications for improving phenology models and could therefore advance our understanding of the interplay between spring phenology and carbon fluxes.

Moxibustion-mediated alleviation of synovitis in rats with rheumatoid arthritis through the regulation of NLRP3 inflammasome by modulating neutrophil extracellular traps.

Purpose: This study investigates the potential mechanism of moxibustion in the treatment of rheumatoid arthritis (RA) by regulating the neutrophil extracellular trap (NET)/NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome axis with the use of a rat model with adjuvant arthritis (AA). Methods: Four groups, including normal control (NC), AA, moxibustion (MOX), and chlor-amidine (Cl-amidine) were created from 24 Wistar male rats (6 rats/group). After the intervention and treatment respectively, the joint swelling degree (JSD) and arthritis index (AI) were compared. The pathological changes of synovium were observed with hematoxylin and eosin staining and transmission electron microscopy. The formation of NETs in synovial tissues was detected with immunofluorescence staining. The protein expression of myeloperoxidase (MPO), neutrophil elastase (NE), citrullinated histone (Cit-H3), acyl arginine deiminase 4 (PAD-4), and NLRP3 was measured in the synovium of rat ankle joints with western blotting, and the levels of anti-cyclic citrullinated peptide antibody (CCP-Ab) and interleukin (IL)-1ß were examined in rat serum with ELISA. Results: AA modeling markedly increased JSD, AI, synovial protein expression of MPO, NE, Cit-H3, PAD-4, and NLRP3, and serum levels of CCP-Ab and IL-1ß in rats (P < 0.01). JSD and AI, as well as the levels of MPO, NE, Cit-H3, PAD-4, NLRP3, CCP-Ab, and IL-1ß, were significantly lowered in AA rats by MOX and Cl-amidine (P < 0.01). In addition, AA modeling caused severe pathological injury in the synovium of rats, which was annulled by MOX and Cl-amidine. The formation of NETs in synovium was substantially promoted in rats by AA modeling and was significantly reduced in AA rats after the treatment. Conclusion: Moxibustion can markedly alleviate synovitis and repress inflammatory factor release in AA rats, which may be achieved by diminished synthesis of NETs or their constituents and the blocked formation of NLRP3 inflammasome.

Enhancing Electrochemical Signal for Efficient Chiral Recognition by Encapsulating C60 Fullerene into Chiral Lanthanum-Based MOFs.

Chiral metal-organic frameworks (MOFs) have attracted much attention due to their highly tunable regular microporous structures. However, chiral electrochemical recognition based on chiral MOFs is often limited by poor charge separation and slow charge transfer kinetics. In this case, C60 can be encapsulated into the cavity of [La(BTB)]n by virtue of host-guest interactions through π-π stacking to synthesize the chiral composite C60@[La(BTB)]n and amplify electrochemically controlled enantioselective interactions with the target enantiomers. A large electrostatic potential difference is generated in chiral C60@[La(BTB)]n due to the host-guest interaction and the inhomogeneity of the charge distribution, leading to the generation of a strong built-in electric field and thus an overall enhancement of the conductivity of the chiral material. Their enantioselective detection of tryptophan enantiomers was demonstrated by electrochemical measurement. The results showed that chiral MOF materials can be used for enantiomeric recognition. It is worth noting that this new material derived from the concept of host-guest interaction to enhance charge separation opens up unprecedented possibilities for future enantioselective recognition and separation.

pH-Tuned Enantioselectivity Reversal in a Defective Chiral Metal Organic Framework.

The introduction of chirality into easy-scalable metal-organic frameworks (MOFs) gives rise to the development of advanced electrochemical sensors. However, integrating chirality by directly connecting metal ions and chiral ligands is unpredictable. Postmodification synthesis is a common method for synthesizing chiral MOFs, but it reduces the size of chiral channels and poses obstacles to the approach of chiral guest molecules. In this work, missing connection defects were introduced into the chiral MOFs through defect engineering strategies, which enhance the recognition of the target enantiomers. pH can tune enantioselectivity reversal in defective chiral MOFs. The chiral MOFs show enantioselectivity for d-Trp at pH = 5 and l-Trp at pH = 8. From the results of zeta potential, regardless of pH 5 or 8, the chiral MOF has a positive potential. The chiral MOFs are positively charged, while tryptophan is negatively charged when pH = 8. The difference in the positive and negative charge interactions between the two amino acids and chiral MOFs leads to chiral recognition. However, the difference in π-π interaction between chiral MOF and Trp enantiomers mainly drives chiral recognition under pH = 5. This study paves a pathway for the synthesis of defective chiral MOFs and highlights the pH-tuned enantioselectivity reversal.

Long-term species-level observations indicate the critical role of soil moisture in regulating China's grassland productivity relative to phenological and climatic factors.

As a sensitive indicator of climate change and a key variable in ecosystem surface-atmosphere interaction, vegetation phenology, and the growing season length, as well as climatic factors (i.e., temperature, precipitation, and sunshine duration) are widely recognized as key factors influencing vegetation productivity. Recent studies have highlighted the importance of soil moisture in regulating grassland productivity. However, the relative importance of phenology, climatic factors, and soil moisture to plant species-level productivity across China's grasslands remains poorly understood. Here, we use nearly four decades (1981 to 2018) of in situ species-level observations from 17 stations distributed across grasslands in China to examine the key mechanisms that control grassland productivity. The results reveal that soil moisture is the strongest determinant of the interannual variability in grassland productivity. In contrast, the spring/autumn phenology, the length of vegetation growing season, and climate factors have relatively minor impacts. Generally, annual aboveground biomass increases by 3.9 to 25.3 g∙m2 (dry weight) with a 1 % increase in growing season mean soil moisture across the stations. Specifically, the sensitivity of productivity to moisture in wetter and colder environments (e.g., alpine meadows) is significantly higher than that in drier and warmer environments (e.g., temperate desert steppes). In contrast, the sensitivity to the precipitation of the latter is greater than the former. The effect of soil moisture is the most pronounced during summer. Dominant herb productivity is more sensitive to soil moisture than the others. Moreover, multivariate regression analyses show that the primary climatic factors and their attributions to variations in soil moisture differ among the stations, indicating the interaction between climate and soil moisture is very complex. Our study highlights the interspecific difference in the soil moisture dependence of grassland productivity and provides guidance to climate change impact assessments in grassland ecosystems.

Moxibustion intervention improves synovitis by down-regulating NLRP3/Caspase-1/IL-1ß signaling of synovial tissue in rats with adjuvant arthritis. / 基于NLRP3/Caspase-1/IL-1ßä¿¡å·é€šè·¯æŽ¢è®¨è‰¾ç¸æ”¹å–„ä½å‰‚æ€§å ³èŠ‚ç‚Žå¤§é¼ æ»‘è†œç‚Žçš„æœºåˆ¶.

OBJECTIVES: To observe the effect of moxibustion on activities of NOD-like receptor family protein 3 (NLRP3)/cysteine aspartic acid specific protease-1 (Caspase-1)/interleukin-1ß (IL-1ß) signaling pathway in rats with adjuvant arthritis (AA), so as to explore its mechanisms underlying improvement of rheumatoid arthritis (RA). Me-thods Thirty male Wistar rats were randomly divided into normal control, AA model and moxibustion groups, with 10 rats in each group. The AA model was replicated by raising in wind, cold and damp environment combined with complete Freund's adjuvant injection. In the moxibustion group, moxibustion was applied to bilateral "Shenshu" (BL23) and "Zusanli"(ST36) for 20 min each time, once daily for 21 days. Changes of joint swelling degree (JSD) and arthritis index (AI) in each group were observed. The ultrastructural changes of synovial cells in each group were observed by transmission electron microscopy. The protein expression levels of NLRP3, apoptosis-associated speck-like protein (ASC), Caspase-1, tumor necrosis factor-α (TNF-α) and IL-1ß in the synovial tissues of the knee joint were measured by Western blot. RESULTS: Compared with the normal control group, JSD, AI and the protein expressions of NLRP3, ASC, Caspase-1, TNF-α and IL-1ß in the synovial tissues were significantly increased (P<0.01) in the model group. In comparison with the model group, JSD, AI and the protein expression levels of NLRP3, ASC, Caspase-1, TNF-α and IL-1ß were significantly decreased (P<0.01) in the moxibustion group. Results of transmission electron microscope showed an irregular and vague nuclear membrane of synovial cells, and unclear mitochondrial membrane boundary with sparse, swelling crests in the model group, which was relatively milder in the damage degree in the moxibustion group. CONCLUSIONS: Moxibustion can relieve the inflammatory response in the synovial membrane of AA rats, which may be related to its function in down-regulating synovial NLRP3/Caspase-1/IL-1ß inflammatory signaling.

Biology of breast cancer brain metastases and novel therapies targeting the blood brain barrier: an updated review.

Brain metastasis (BM) is a critical cause of morbidity and mortality in patients with breast cancer (BC). Compared with other cancer cells, BC cells (BCs) exhibit special features in the metastatic process. However, the underlying mechanisms are still unclear, especially the crosstalk between tumour cells and the microenvironment. To date, novel therapies for BM, including targeted therapy and antibody‒drug conjugates, have been developed. Due to an improved understanding of the blood‒brain barrier (BBB) and blood-tumour barrier (BTB), the development and testing of therapeutic agents in clinical phases have substantially increased. However, these therapies face a major challenge due to the low penetration of the BBB or BTB. As a result, researchers have increasingly focused on finding ways to promote drug penetration through these barriers. This review provides an updated overview of breast cancer brain metastases (BCBM) and summarizes the newly developed therapies for BCBM, especially drugs targeting the BBB or BTB.

Factors influencing the diagnostic and prognostic values of circulating tumor cells in breast cancer: a meta-analysis of 8,935 patients.

Background: Circulating tumor cells (CTCs) could serve as a predictive biomarker in breast cancer (BC). Due to its high heterogeneity, the diagnostic and prognostic values of CTC are challenging. Methods: We searched published studies from the databases of PubMed, Cochrane Library, Embase, and MEDLINE. The detection capability and hazard ratios (HRs) of CTCs were extracted as the clinical diagnosis and prognosis evaluation. Subgroup analyses were divided according to the detection methods, continents, treatment periods, therapeutic plans, and cancer stages. Results: In this study, 35 publications had been retrieved with 8,935 patients enrolled. The diagnostic efficacy of CTC detection has 74% sensitivity and 98% specificity. The positive CTC detection (CTC+) would predict worse OS and PFS/DFS in both mid-therapy and post-therapy (HROS, 3.09; 95% CI, 2.17-4.39; HRPFS/DFS, 2.06; 95% CI, 1.72-2.47). Moreover, CTC+ indicated poor survival irrespective of the treatment phases and sampling times (HROS, 2.43; 95% CI, 1.85-3.19; HRPFS/DFS, 1.82; 95% CI, 1.66-1.99). The CTC+ was associated with poor survival regardless of the continents of patients (HROS = 2.43; 95% CI, 1.85-3.19). Conclusion: Our study suggested that CTC+ was associated with a worse OS and PFS/DFS in the Asian population. The detection method, the threshold level of CTC+, therapeutic approaches, and sampling times would not affect its diagnostic and prognostic values.

Ferroptosis as an emerging target in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology. Due to the rise in the incidence rate of RA and the limitations of existing therapies, the search for new treatment strategies for RA has become a global focus. Ferroptosis is a novel programmed cell death characterized by iron-dependent lipid peroxidation, with distinct differences from apoptosis, autophagy, and necrosis. Under the conditions of iron accumulation and the glutathione peroxidase 4 (GPX4) activity loss, the lethal accumulation of lipid peroxide is the direct cause of ferroptosis. Ferroptosis mediates inflammation, oxidative stress, and lipid oxidative damage processes, and also participates in the occurrence and pathological progression of inflammatory joint diseases including RA. This review provides insight into the role and mechanism of ferroptosis in RA and discusses the potential and challenges of ferroptosis as a new therapeutic strategy for RA, with an effort to provide new targets for RA prevention and treatment.

Increased productivity of temperate vegetation in the preceding year drives early spring phenology in the subsequent year in northern China.

Under global warming, rising temperature have advanced spring phenology in recent decades. However, the internal physiological mechanisms driving changes in spring phenology still remain poorly understood. Here, we investigated the effects of temperate vegetation gross primary productivity (GPP) during the preceding year on spring phenology of the subsequent year based on the start of growing season (SOS) extracted from NDVI datasets between 1982 and 2015. We found that the preceding year's GPP had an effect on the subsequent year's SOS, equivalent to 33 %-50 % of effect of the preseason's mean temperature. Specifically, in the temperate and semi-humid or humid conditions, the preceding year's GPP had a stronger effect on SOS than in boreal or semi-arid conditions. In addition, the SOS of the dwarf vegetation, with less transport pressure and higher carbon concentrations, was more sensitive to the preceding year's GPP than that of tall forests. We found the effects of the preceding year's GPP on SOS varied with space and vegetation types. Therefore, the physiological mechanism should be considered in future spring phenology model separately according to space and vegetation types, to improve the accuracy of future phenology and then global carbon sequestration predictions.

Adamantaniline Derivatives Target ATP5B to Inhibit Translation of Hypoxia Inducible Factor-1α.

Hypoxia inducible factor-1α (HIF-1α) plays a critical role in cellular adaptation to hypoxia and it is a potential therapeutic target for anti-cancer drugs. Applying high-throughput screening, here it is found that HI-101, a small molecule containing an adamantaniline moiety, effectively reduces HIF-1α protein expression. With the compound as a hit, a probe (HI-102) is developed for target identification by affinity-based protein profiling. The catalytic ß subunit of mitochondrial FO F1 -ATP synthase, ATP5B, is identified as the binding protein of HI-derivatives. Mechanistically, HI-101 promotes the binding of HIF-1α mRNA to ATP5B, thus inhibiting HIF-1α translation and the following transcriptional activity. Further modifications of HI-101 lead to HI-104, a compound with good pharmacokinetic properties, exhibiting antitumor activity in MHCC97-L mice xenograft model, and HI-105, the most potent compound with an IC50 of 26 nm. The findings provide a new strategy for further developing HIF-1α inhibitors by translational inhibition through ATP5B.

Generation of Human Blood Vessel and Vascularized Cerebral Organoids.

Brain organoids have been widely used to study diseases and the development of the nervous system. Many reports have investigated the application of brain organoids, but most of these models lack vascular structures, which play essential roles in brain development and neurological diseases. The brain and blood vessels originate from two different germ layers, making it difficult to induce vascularized brain organoids in vitro. We developed this protocol to generate brain-specific blood vessel and cerebral organoids and then fused them at a specific developmental time point. The fused cerebral organoids exhibited robust vascular network-like structures, which allows simulating the in vivo developmental processes of the brain for further applications in various neurological diseases. Key Features • Culturing vascularized brain organoids using human embryonic stem cells (hESCs). • The new approach generates not only neural cells and vessel-like networks but also brain-resident microglia immune cells in a single organoid.

Celastrol suppresses colorectal cancer via covalent targeting peroxiredoxin 1.

As a terpenoids natural product isolated from the plant Thunder God Vine, Celastrol is widely studied for its pharmacological activities, including anti-tumor activities. The clinical application of Celastrol is strictly limited due to its severe side effects, whereas previously revealed targets and mechanism of Celastrol seldom reduce its in vivo toxicity via structural optimization. Target identification has a far-reaching influence on the development of innovative drugs, and omics data has been widely used for unbiased target prediction. However, it is difficult to enrich target of specific phenotype from thousands of genes or proteins, especially for natural products with broad promising activities. Here, we developed a text-mining-based web-server tool to enrich targets from omics data of inquired compounds. Then peroxiredoxin 1 (PRDX1) was identified as the ROS-manipulating target protein of Celastrol in colorectal cancer. Our solved high-resolution crystal structure revealed the unique covalent binding mode of Celastrol with PRDX1. New derivative compound 19-048 with improved potency against PRDX1 and selectivity towards PRDX2~PRDX6 were synthesized based on crystal structure analysis. Both Celastrol and 19-048 effectively suppressed the proliferation of colorectal cancer cells. The anti-tumor efficacy of Celastrol and 19-048 was significantly diminished on xenograft nude mice bearing PRDX1 knock-down colorectal cancer cells. Several downstream genes of p53 signaling pathway were dramatically up-regulated with Celastrol or 19-048 treatment. Our findings reveal that the side effects of Celastrol could be reduced via structural modification, and PRDX1 inhibition is promising for the treatment of colorectal cancer.

Efficacy of Infants Release of Ankyloglossia on Speech Articulation: A Randomized Trial.

PURPOSE: The relationship between ankyloglossia and speech is controversial. Our objective in the present study was to determine the most appropriate intervention and optimal timing for infants with speech articulation caused by ankyloglossia. PATIENTS AND METHODS: A total of 341 pediatric patients (aged 2 to 5 years) being referred for speech concerns due to ankyloglossia were enrolled in a randomized trial and assigned to either a surgical intervention (N = 166) or a no surgical intervention (N = 175) group. Subsequently, patients were further categorized into 3 groups according to age: 2 to < 3 years, 3 to < 4 years, and 4 to < 5 years. Measures of tongue appearance, tongue mobility, speech production, and parent and clinician intelligibility ratings were collected at preintervention (T0), 2-month postintervention (T1), 6-month postintervention (T2), and 12-month postintervention (T3). RESULTS: No statistically significant difference was found between surgical intervention and no surgical intervention groups for tongue appearance, tongue mobility, speech production, and intelligibility in the 2 to < 3 years age. However, there was significantly improved speech production and intelligibility in the surgical intervention group when compared to the no surgical intervention group in the 3 to < 4 and 4 to < 5 years old age. CONCLUSION: Surgical intervention should not be performed too early for infants aged 2 to < 3 years with speech articulation caused by ankyloglossia, but rather watch and wait for the physiological growth of the lingual frenulum. The optimal timing range for surgical intervention is 4 to 5 years. This should provide certain significant guidance for infants with speech articulation caused by ankyloglossia.

Ultra-slim flexible bronchoscopy-guided topical hemostatic drugs administration for the management of life-threatening refractory pulmonary hemorrhage in a preterm infant: Case report.

Pulmonary hemorrhage (PH) is a rare acute catastrophic event with high mortality among neonates, especially preterm infants. Primary treatments included pulmonary surfactant, high-frequency oscillatory ventilation, epinephrine, coagulopathy management, and intermittent positive pressure ventilation. However, there are still challenges in diagnosing and treating refractory or focal pulmonary hemorrhages. Ultra-slim bronchoscopy has been widely used in the field of critically ill children and is increasingly being done in neonates with critical respiratory disease in recent years. In this study, we report a case with refractory pulmonary hemorrhage in premature infants, which was finally diagnosed as localized hemorrhage in the upper left lobe and cured by ultra-slim bronchoscopy-guided topical hemostatic drug administration. Bronchoscopy is an optional, safe, and practicable technique for early diagnosis and direct injection therapy of neonatal PH in managing life-threatening PH.