The ribosomal chaperone NACA recruits PHD2 to cotranslationally modify HIF-α.

Prolyl hydroxylase domain protein 2 (PHD2)-catalyzed modification of hypoxia-inducible factor (HIF)-α is a key event in oxygen sensing. We previously showed that the zinc finger of PHD2 binds to a Pro-Xaa-Leu-Glu (PXLE) motif. Here, we show that the zinc finger binds to this motif in the ribosomal chaperone nascent polypeptide complex-α (NACA). This recruits PHD2 to the translation machinery to cotranslationally modify HIF-α. Importantly, this cotranslational modification is enhanced by a translational pause sequence in HIF-α. Mice with a knock-in Naca gene mutation that abolishes the PXLE motif display erythrocytosis, a reflection of HIF pathway dysregulation. In addition, human erythrocytosis-associated mutations in the zinc finger of PHD2 ablate interaction with NACA. Tibetans, who have adapted to the hypoxia of high altitude, harbor a PHD2 variant that we previously showed displays a defect in zinc finger binding to p23, a PXLE-containing HSP90 cochaperone. We show here that Tibetan PHD2 maintains interaction with NACA, thereby showing differential interactions with PXLE-containing proteins and providing an explanation for why Tibetans are not predisposed to erythrocytosis.

Arabidopsis FIN219/JAR1 interacts with phytochrome A under far-red light and jasmonates in regulating hypocotyl elongation via a functional demand manner.

Integration of light and phytohormones is essential for plant growth and development. FAR-RED INSENSITIVE 219 (FIN219)/JASMONATE RESISTANT 1 (JAR1) participates in phytochrome A (phyA)-mediated far-red (FR) light signaling in Arabidopsis and is a jasmonate (JA)-conjugating enzyme for the generation of an active JA-isoleucine. Accumulating evidence indicates that FR and JA signaling integrate with each other. However, the molecular mechanisms underlying their interaction remain largely unknown. Here, the phyA mutant was hypersensitive to JA. The double mutant fin219-2phyA-211 showed a synergistic effect on seedling development under FR light. Further evidence revealed that FIN219 and phyA antagonized with each other in a mutually functional demand to modulate hypocotyl elongation and expression of light- and JA-responsive genes. Moreover, FIN219 interacted with phyA under prolonged FR light, and MeJA could enhance their interaction with CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) in the dark and FR light. FIN219 and phyA interaction occurred mainly in the cytoplasm, and they regulated their mutual subcellular localization under FR light. Surprisingly, the fin219-2 mutant abolished the formation of phyA nuclear bodies under FR light. Overall, these data identified a vital mechanism of phyA-FIN219-COP1 association in response to FR light, and MeJA may allow the photoactivated phyA to trigger photomorphogenic responses.

A coherent FOXO3-SNAI2 feed-forward loop in autophagy.

SignificanceUnderstanding autophagy regulation is instrumental in developing therapeutic interventions for autophagy-associated disease. Here, we identified SNAI2 as a regulator of autophagy from a genome-wide screen in HeLa cells. Upon energy stress, SNAI2 is transcriptionally activated by FOXO3 and interacts with FOXO3 to form a feed-forward regulatory loop to reinforce the expression of autophagy genes. Of note, SNAI2-increased FOXO3-DNA binding abrogates CRM1-dependent FOXO3 nuclear export, illuminating a pivotal role of DNA in the nuclear retention of nucleocytoplasmic shuttling proteins. Moreover, a dFoxO-Snail feed-forward loop regulates both autophagy and cell size in Drosophila, suggesting this evolutionarily conserved regulatory loop is engaged in more physiological activities.

Miat and interacting protein Metadherin maintain a stem-like niche to promote medulloblastoma tumorigenesis and treatment resistance.

Long noncoding RNAs (lncRNAs) play essential roles in the development and progression of many cancers. However, the contributions of lncRNAs to medulloblastoma (MB) remain poorly understood. Here, we identify Miat as an lncRNA enriched in the sonic hedgehog group of MB that is required for maintenance of a treatment-resistant stem-like phenotype in the disease. Loss of Miat results in the differentiation of tumor-initiating, stem-like MB cells and enforces the differentiation of tumorigenic stem-like MB cells into a nontumorigenic state. Miat expression in stem-like MB cells also facilitates treatment resistance by down-regulating p53 signaling and impairing radiation-induced cell death, which can be reversed by therapeutic inhibition of Miat using antisense oligonucleotides. Mechanistically, the RNA binding protein Metadherin (Mtdh), previously linked to resistance to cytotoxic therapy in cancer, binds to Miat in stem-like MB cells. Like the loss of Miat, the loss of Mtdh reduces tumorigenicity and increases sensitivity to radiation-induced death in stem-like MB cells. Moreover, Miat and Mtdh function to regulate the biogenesis of several microRNAs and facilitate tumorigenesis and treatment resistance. Taken together, these data reveal an essential role for the lncRNA Miat in sustaining a treatment-resistant pool of tumorigenic stem-like MB cells.

Variability in Leaf Color Induced by Chlorophyll Deficiency: Transcriptional Changes in Bamboo Leaves.

The diversity of leaf characteristics, particularly leaf color, underscores a pivotal area of inquiry within plant science. The synthesis and functionality of chlorophyll, crucial for photosynthesis, largely dictate leaf coloration, with varying concentrations imparting different shades of green. Complex gene interactions regulate the synthesis and degradation of chlorophyll, and disruptions in these pathways can result in abnormal chlorophyll production, thereby affecting leaf pigmentation. This study focuses on Bambusa multiplex f. silverstripe, a natural variant distinguished by a spectrum of leaf colors, such as green, white, and green-white, attributed to genetic variations influencing gene expression. By examining the physiological and molecular mechanisms underlying chlorophyll anomalies and genetic factors in Silverstripe, this research sheds light on the intricate gene interactions and regulatory networks that contribute to leaf color diversity. The investigation includes the measurement of photosynthetic pigments and nutrient concentrations across different leaf color types, alongside transcriptomic analyses for identifying differentially expressed genes. The role of key genes in pathways such as ALA biosynthesis, chlorophyll synthesis, photosynthesis, and sugar metabolism is explored, offering critical insights for advancing research and plant breeding practices.

Study of Iron Complex Photosensitizer with Hollow Double-Shell Nano Structure Used to Enhance Ferroptosis and Photodynamic Therapy.

Ferroptosis therapy, which uses ferroptosis inducers to produce lethal lipid peroxides and induce tumor cell death, is considered a promising cancer treatment strategy. However, challenges remain regarding how to increase the accumulation of reactive oxygen species (ROS) in the tumor microenvironment (TME) to enhance antitumor efficacy. In this study, a hyaluronic acid (HA) encapsulated hollow mesoporous manganese dioxide (H-MnO2 ) with double-shell nanostructure is designed to contain iron coordinated cyanine near-infrared dye IR783 (IR783-Fe) for synergistic ferroptosis photodynamic therapy against tumors. The nano photosensitizer IR783-Fe@MnO2 -HA, in which HA actively targets the CD44 receptor, subsequently dissociates and releases Fe3+ and IR783 in acidic TME. First, Fe3+ consumes glutathione to produce Fe2+ , which promotes the Fenton reaction in cells to produce hydroxyl free radicals (·OH) and induce ferroptosis of tumor cells. In addition, MnO2 catalyzes the production of O2 from H2 O2 and enhances the production of singlet oxygen (1 O2 ) by IR783 under laser irradiation, thus increasing the production and accumulation of ROS to provide photodynamic therapy. The highly biocompatible IR783-Fe@MnO2 -HA nano-photosensitizers have exhibited tumor-targeting ability and efficient tumor inhibition in vivo due to the synergistic effect of photodynamic and ferroptosis antitumor therapies.

FAR-RED INSENSITIVE 219 and phytochrome B corepress shade avoidance via modulating nuclear speckle formation.

Plants can sense the shade from neighboring plants by detecting a reduction of the red:far-red light (R:FR) ratio. Phytochrome B (phyB) is the primary photoreceptor that perceives shade light and regulates jasmonic acid (JA) signaling. However, the molecular mechanisms underlying phyB and JA signaling integration in shade responses remain largely unknown. Here, we show the interaction of phyB and FAR-RED INSENSITIVE 219 (FIN219)/JASMONATE RESISTANT1 (JAR1) in a functional demand manner in Arabidopsis (Arabidopsis thaliana) seedling development. Genetic evidence and interaction studies indicated that phyB and FIN219 synergistically and negatively regulate shade-induced hypocotyl elongation. Moreover, phyB interacted with various isoforms of FIN219 under high and low R:FR light. Methyl jasmonate (MeJA) treatment, FIN219 mutation, and PHYBOE digalactosyldiacylglycerol synthase1-1 (dgd1-1) plants, which show increased levels of JA, altered the patterns of phyB-associated nuclear speckles under the same conditions. Surprisingly, PHYBOE dgd1-1 showed a shorter hypocotyl phenotype than its parental mutants under shade conditions. Microarray assays using PHYBOE and PHYBOE fin219-2 indicated that PHYB overexpression substantially affects defense response-related genes under shade light and coregulates expression of auxin-responsive genes with FIN219. Thus, our findings reveal that phyB substantially crosstalks with JA signaling through FIN219 to modulate seedling development under shade light.

Climate-associated variation in the drivers of benthic macroinvertebrate species-area relationships across shallow freshwater lakes.

The island species-area relationship (ISAR) describes how species richness increases with increasing area of a given island or island-like habitat, such as freshwater lakes. While the ISAR is one of the most common phenomena observed in ecology, there is variation in both the form of the relationship and its underlying mechanisms. We compiled a global data set of benthic macroinvertebrates from 524 shallow freshwater lakes, ranging from 1 to 293,300 ha in area. We used individual-based rarefaction to determine the degree to which ISAR was influenced by mechanisms other than passive sampling (larger islands passively sample more individuals from the regional pool and, therefore, have more species than smaller islands), which would bias results away from expected relationships between rarefied species richness (and other measures that capture relative abundances) and lake area. We also examined how climate may alter the shape of the ISARs. We found that both rarefied species richness (the number of species standardized by area or number of individuals) and a measure of evenness emphasizing common species exhibit shallow slopes in relationships with lake area, suggesting that the expected ISARs in these lakes most likely result from passive sampling. While there was considerable variation among ISARs across the investigated lakes, we found an overall positive rarefied ISAR for lakes in warm (i.e. tropical/subtropical) regions (n = 195), and in contrast, an overall negative rarefied ISAR in cool (i.e. north temperate) lakes (n = 329). This suggested that mechanisms beyond passive sampling (e.g. colonization-extinction dynamics and/or heterogeneity) were more likely to operate in warm lakes. One possible reason for this difference is that the area-dependent intensity of fish predation, which can lead to flatter ISARs, is weaker in warmer relative to cooler lakes. Our study illustrates the importance of understanding both the pattern and potential processes underlying the ISARs of freshwater lakes in different climatic regions. Furthermore, it provides a baseline for understanding how further changes to the ecosystem (i.e. in lake area or climate) might influence biodiversity patterns.

Spatial and temporal variation in lake macroinvertebrate communities is decreased by eutrophication.

Eutrophication impacts freshwater ecosystems and biodiversity across the world. While temporal monitoring has shown changes in the nutrient inputs in many areas, how spatial and temporal beta diversity change along the eutrophication gradient under a changing context remains unclear. In this regard, analyses based on time series spanning multiple years are particularly scarce. We sampled benthic macroinvertebrates in 32 sites across three lake habitat types (MACROPHYTE, OPEN WATER, PHYTOPLANKTON) along the eutrophication gradient of Lake Taihu in four seasons from 2007 to 2019. Our purpose was to identify the relative contributions of spatial and temporal dissimilarity (i.e., inter-annual dissimilarity and seasonal dissimilarity) to overall benthic biodiversity. We also examined spatio-temporal patterns in community assembly mechanisms and how associated variation in benthic macroinvertebrate communities responded to nutrient indicators. Results showed that eutrophication caused macroinvertebrate community homogenization both along spatial and temporal gradients. Though spatial variability dominated the variation of species richness, abundance and community dissimilarity, seasons within years dissimilarity, inter-annual dissimilarity and seasonal dissimilarity were much more sensitive to eutrophication. Moreover, eutrophication inhibited a strong environmental control in benthic macroinvertebrate community assembly, including a dominant role of deterministic process in the spatial variation of macroinvertebrate communities and transition from stochastic to deterministic process in the temporal assembly of macroinvertebrate communities along the eutrophication gradient. In addition, some sites in PHYTOPLANKTON habitats showed similar spatial dissimilarity and spatial SES as sites in MACROPHYTE habitats, and the decreased spatial dissimilarity of three habitats implying that lake ecosystem recovery projects have achieved their goal at least to a certain degree.

Mechanistic insights and implications of FOXO-SNAI interplay.

Autophagy promotes both health and disease, depending on tissue types and genetic contexts, yet the regulatory mechanism remain incompletely understood. Our recent publication has uncovered a coherent FOXO-SNAI feed-forward loop in autophagy, which is evolutionarily conserved from Drosophila to human. In addition, it's revealed that DNA binding plays a critical role in intracellular localization of nucleocytoplasmic shuttling proteins. Based on these findings, herein we further integrate mechanistic insights of FOXO-SNAI regulatory interplay in autophagy and unravel the potential link of FOXO-induced autophagy with SNAI in diseases. Besides, the generality of DNA-retention mechanism on transcription factor nuclear localization is illustrated with wide-ranging discussion, and more functions potentially regulated by FOXO-SNAI feedforward loop are provided. Elucidation of these unsolved paradigms will expand the understanding of FOXO-SNAI interplay and facilitate the development of new therapeutics targeting FOXO-SNAI axis in diseases.

CHRISTMAS: Chiral Pair Isobaric Labeling Strategy for Multiplexed Absolute Quantitation of Enantiomeric Amino Acids.

Amino acids (AAs) in the d-form are involved in multiple pivotal neurological processes, although their l-enantiomers are most commonly found. Mass spectrometry-based analysis of low-abundance d-AAs has been hindered by challenging enantiomeric separation from l-AAs, low sensitivity for detection, and lack of suitable internal standards for accurate quantification. To address these critical gaps, N,N-dimethyl-l-leucine (l-DiLeu) tags are first validated as novel chiral derivatization reagents for chromatographic separation of 20 pairs of d/l-AAs, allowing the construction of a 4-plex isobaric labeling strategy for enantiomer-resolved quantification through single step tagging. Additionally, the creative design of N,N-dimethyl-d-leucine (d-DiLeu) reagents offers an alternative approach to generate analytically equivalent internal references of d-AAs using d-DiLeu-labeled l-AAs. By labeling cost-effective l-AA standards using paired d- and l-DiLeu, this approach not only enables absolute quantitation of both d-AAs and l-AAs from complex biological matrices with enhanced precision but also significantly boosts the combined signal intensities from all isobaric channels, greatly improving the detection and quantitation of low-abundance AAs, particularly d-AAs. We term this quantitative strategy CHRISTMAS, which stands for chiral pair isobaric labeling strategy for multiplexed absolute quantitation. Leveraging the ion mobility collision cross section (CCS) alignment, interferences from coeluting isomers/isobars are effectively filtered out to provide improved quantitative accuracy. From wild-type and Alzheimer's disease (AD) mouse brains, we successfully quantified 20 l-AAs and 5 d-AAs. The significant presence and differential trends of certain d-AAs compared to those of their l-counterparts provide valuable insights into the involvement of d-AAs in aging, AD progression, and neurodegeneration.

Halide perovskites enable polaritonic XY spin Hamiltonian at room temperature.

Exciton polaritons, the part-light and part-matter quasiparticles in semiconductor optical cavities, are promising for exploring Bose-Einstein condensation, non-equilibrium many-body physics and analogue simulation at elevated temperatures. However, a room-temperature polaritonic platform on par with the GaAs quantum wells grown by molecular beam epitaxy at low temperatures remains elusive. The operation of such a platform calls for long-lifetime, strongly interacting excitons in a stringent material system with large yet nanoscale-thin geometry and homogeneous properties. Here, we address this challenge by adopting a method based on the solution synthesis of excitonic halide perovskites grown under nanoconfinement. Such nanoconfinement growth facilitates the synthesis of smooth and homogeneous single-crystalline large crystals enabling the demonstration of XY Hamiltonian lattices with sizes up to 10 × 10. With this demonstration, we further establish perovskites as a promising platform for room temperature polaritonic physics and pave the way for the realization of robust mode-disorder-free polaritonic devices at room temperature.

Bispecific antibody targeting both B7-H3 and PD-L1 exhibits superior antitumor activities.

Clinical application of PD-1 and PD-L1 monoclonal antibodies (mAbs) is hindered by their relatively low response rates and the occurrence of drug resistance. Co-expression of B7-H3 with PD-L1 has been found in various solid tumors, and combination therapies that target both PD-1/PD-L1 and B7-H3 pathways may provide  additional therapeutic benefits. Up to today, however, no bispecific antibodies targeting both PD-1 and B7-H3 have reached the clinical development stage. In this study, we generated a stable B7-H3×PD-L1 bispecific antibody (BsAb) in IgG1-VHH format by coupling a humanized IgG1 mAb against PD-L1 with a humanized camelus variable domain of the heavy-chain of heavy-chain antibody (VHH) against human B7-H3. The BsAb exhibited favorable thermostability, efficient T cell activation, IFN-γ production, and antibody-dependent cell-mediated cytotoxicity (ADCC). In a PBMC humanized A375 xenogeneic tumor model, treatment with BsAb (10 mg/kg, i.p., twice a week for 6 weeks) showed enhanced antitumor activities compared to monotherapies and, to some degree, combination therapies. Our results suggest that targeting both PD-1 and B7-H3 with BsAbs increases their specificities to B7-H3 and PD-L1 double-positive tumors and induces a synergetic effect. We conclude that B7-H3×PD-L1 BsAb is favored over mAbs and possibly combination therapies in treating B7-H3 and PD-L1 double-positive tumors.

Outer dynein arm docking complex subunit 2 polymorphism rs7893462 modulates hepatocellular carcinoma susceptibility and can serve as an overall survival biomarker for hepatitis B virus-related hepatocellular carcinoma after hepatectomy: a cohort study with a long-term follow-up.

BACKGROUND: Genetic variants of outer dynein arm docking complex subunit 2 (ODAD2) have been reported to be closely associated with primary ciliary dyskinesia and colorectal cancer in previous studies, but the association of genetic variants of ODAD2 with hepatocellular carcinoma (HCC) has not been reported. METHODS: We enrolled 80 healthy subjects and 468 Guangxi hepatitis B virus (HBV)-related HCC patients in this study. A case-control study method was used to explore the association of different ODAD2-rs7893462 genotypes with hepatocarcinogenesis. A comprehensive survival analysis was used to explore the association of rs7893462 with the prognosis of HBV-related HCC in Guangxi. RESULTS: Through a case-control study, we observed that patients carrying the G allele of rs7893462 had a markedly increased susceptibility to hepatocarcinogenesis (odds ratio = 1.712, 95% confidence interval = 1.032-2.839, P = 0.037). We found that there were significant prognosis differences among three different genotypes of rs7893462. Nomogram analysis suggested that the contribution of rs7893462 polymorphisms to the prognosis of HBV-related HCC was second only to the BCLC stage. Stratified survival analysis suggested that the AG genotype of rs7893462 was an independent prognostic risk factor for HBV-related HCC. Joint effect survival analysis also observed that the AG genotype of rs7893462 combined with clinical parameters could significantly identify HBV-related HCC patients with different prognostic outcomes more accurately, and the AG genotype was also observed to be independent of clinical factors in HBV-related HCC survival. CONCLUSION: The ODAD2-rs7893462 polymorphisms can be used as an independent prognostic indicator of HBV-related HCC overall survival and are significantly associated with susceptibility to hepatocarcinogenesis.

Clinical Significance of Visual Training in Improving Visual Function After Retinal Detachment in Adolescents.

Context: Epidemiological data has shown that retinal detachment (RD) can occur at any age but has a poor prognosis in the adolescent population, which can cause huge obstacles to their life and learning. Although medications can achieve some curative effect, they have potential side effects and differences in individual efficacy. Objective: • The study intended to explore the clinical significance of visual training in improving recovery of postoperative visual function after external reduction of retinal detachment in adolescent patients. Design: The research team designed a prospective randomized controlled study. Setting: The study took place at Guiyang First People's Hospital in Guiyang, Guizhou, China. Participants: Participants were 110 adolescents with retinal detachments who underwent external reduction surgery, each on one eye for 110 eyes in total, and who were patients at the hospital between June 2015 and June 2019. Intervention: The research team assigned 52 participants to the visual-function training group, the intervention group, and 58 participants to the control group, according to the random-number-table method. Each group participated in training method for six months. Outcome Measures: To compare the groups, the research team measured visual function using the Visual Function scale (VF), binocular fusion function using the Worth Four Light Test (W4LT), and stereoscopic vision using the Titmus Stereo Test. The team obtained preoperative and postoperative data-at baseline, one day before surgery and postoperatively at one month and 3 months, and postintervention at 6 months. Results: Both groups had visual impairment after surgery. For visual function, the intervention group's scores after surgery increased gradually and were significantly higher than those of the control group at each follow-up time (P < .05). No significant difference in binocular fusion function existed between the groups at baseline or at one month after surgery (P > .05). At 3 months after surgery and postintervention, the proportions of participants in the intervention group with normal binocular fusion function were 86.54% and 88.46%, respectively, compared to that of the control group, at 68.97% and 70.69%, respectively. The intervention group's recovery was significantly better than that of the control group at 3 months after surgery and postintervention, at P < .028 and P < .022, respectively. No significant difference existed between the groups in stereoscopic vision at baseline, at 9.62% and 12.07%, respectively (P > .05). The proportion of participants in the intervention group with normal, binocular, stereoscopic vision increased gradually, and at one and 3 months after surgery and postintervention was 67.31%, 82.69%, and 88.46%, respectively. The intervention group's recovery was significantly better than that of the control group at one and 3 months after surgery and postintervention, at P < .028, P < .010, and P < .013, respectively. Conclusions: Visual training can effectively promote the recovery of visual function after external reduction of RD in adolescents and improve patients' prognoses. Moreover, long-term persistence can achieve significant effects, making the training worthy of clinical promotion.

Electrically Pumped Polarized Exciton-Polaritons in a Halide Perovskite Microcavity.

Recently, exciton-polaritons in lead halide perovskite microcavities have been extensively investigated to address striking phenomena such as polariton condensation and quantum emulation. However, a critical step in advancing these findings into practical applications, i.e., realizing electrically pumped perovskite polariton light-emitting devices, has not yet been presented. Here, we devise a new method to combine the device with a microcavity and report the first halide perovskite polariton light-emitting device. Specifically, the device is based on a CsPbBr3 capacitive structure, which can inject the electrons and holes from the same electrode, conducive to the formation of excitons and simultaneously maintaining the high quality of the microcavity. In addition, highly polarized polariton emissions have been demonstrated due to the optical birefringence in the CsPbBr3 microplate. This work paves the way for realizing practical polaritonic devices such as high-speed light-emitting devices for information communications and inversionless electrically pumped lasers based on perovskites.

Clinicopathological features and resistance mechanisms in HIP1-ALK-rearranged lung cancer: A multicenter study.

Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) respond well to ALK tyrosine kinase inhibitors (TKIs), and echinoderm microtubule-associated protein-like 4 (EML4)-ALK-rearranged NSCLC accounts for the majority of those patients. However, few studies have evaluated ALK-TKIs treatment for patients with huntingtin-interacting protein 1 (HIP1)-ALK fusions. This retrospective study evaluated the clinicopathological characteristics, genomic features, response to ALK-TKIs, and resistance mechanisms in 11 cases with HIP1-ALK fusions from five Chinese centers. Patients who received crizotinib at the Chinese centers had an objective response rate of 90% [9/10 cases, 95% confident index (CI): 54.1%-99.5%], median progression-free survival of 17.9 months (95% CI: 5.8-NA months), and median overall survival of 58.8 months (95% CI: 24.7-NA months). One patient who received first-line lorlatinib treatment achieved partial response for > 26.5 months. Despite the small sample size, HIP1-ALK (H21:A20) variant was the most common variant (four of 11 cases, 36.4%) and associated with better outcomes. Among the 11 cases, there were eight patients having available specimens for genetic testing before ALK-TKIs treatment and four patients undergoing biopsy after ALK-TKIs failure. The most common coexisting gene was TP53 among 11 patients and two of four patients after crizotinib failure harbored acquired ALK mutations (e.g., L1152V/Q1146K and L1196M). Brigatinib treatment appeared to be effective for a patient who failed crizotinib treatment because of the L1152V/Q1146K mutations, which might be related to increased binding affinity to these mutants. Although HIP1-ALK-rearranged NSCLC appears to initially respond well to ALK-TKIs, crizotinib resistance may be correlated with the AKAP9-BRAF fusion, ALK compound mutations (L1152V/Q1146K), and the ALK L1196M mutation. Larger studies are needed to evaluate the significance of HIP1-ALK-rearranged NSCLC.

Robot-assisted laparoscopic enucleation in the treatment of leiomyosarcoma of urinary bladder: A case report. / æœºå™¨äººè¾ åŠ©è ¹è ”é•œä¸‹å‰œé™¤æœ¯æ²»ç–—è†€èƒ±å¹³æ»‘è‚Œè‚‰ç˜¤1例.

Leiomyosarcoma of urinary bladder (LMS-UB) is a highly malignant mesenchymal tumor, accounting for less than 0.5% of all bladder malignancies, with a predominant clinical presentation of hematuria. Here we report a case of low-grade LMS-UB. A 44-year-old male patient was admitted to the hospital with urodynia for 2 weeks. The patient's pelvis CT showed a mass on the right part of the bladder. For this reason, he was initially diagnosed with bladder cancer. We performed a robot-assisted laparoscopic enucleation of the bladder tumor and low-grade LMS-UB was diagnosed with the histopathological examination. He underwent 5 cycles of adjuvant chemotherapy after surgery. At 19months postoperative follow-up, the patient had no symptoms, recurrence, or distant metastasis. There is no report on the treatment of LMS-UB with minimally invasive enucleation worldwide. This case provides a new comprehensive treatment method of enucleation combined with adjuvant chemotherapy for early low-grade LMS-UB to reduce complications and improve patients' quality of life after surgery.

[Effect of breastfeeding on immune function in infants with human cytomegalovirus infection]. / æ¯ä¹³å–‚å »å¯¹äººå·¨ç»†èƒžç— æ¯’æ„ŸæŸ“å©´å„¿å ç–«åŠŸèƒ½çš„å½±å“.

OBJECTIVES: To study the effect of breastfeeding on immune function in infants with human cytomegalovirus (HCMV) infection. METHODS: A retrospective analysis was performed on the medical data of 135 infants with HCMV infection who were admitted to Children's Hospital Affiliated to Zhengzhou University from January 2021 to May 2022, and all these infants received breastfeeding. According to the results of breast milk HCMV-DNA testing, the infants were divided into two groups: breast milk HCMV positive (n=78) and breast milk HCMV negative (n=57). According to the median breast milk HCMV-DNA load, the infants in the breast milk HCMV positive group were further divided into two subgroups: high viral load and low viral load (n=39 each). Related indicators were compared between the breast milk positive and negative HCMV groups and between the breast milk high viral load and low viral load subgroups, including the percentages of peripheral blood lymphocyte subsets (CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells, and CD19+ B cells), CD4+/CD8+ ratio, IgG, IgM, IgA, and urine HCMV-DNA load. RESULTS: There were no significant differences in the percentages of CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells, and CD19+ B cells, CD4+/CD8+ ratio, IgG, IgM, IgA, and urine HCMV-DNA load between the breast milk HCMV positive and HCMV negative groups, as well as between the breast milk high viral load and low viral load subgroups (P>0.05). CONCLUSIONS: Breastfeeding with HCMV does not affect the immune function of infants with HCMV infection.

Less Configuration and More Dimensionality: Preparative Heart-Cut Multidimensional Liquid Chromatography Based on Trapping Arrays.

The resolving power of multiple dimensional liquid chromatography (mD-LC) is multiplicative as it adds dimensions. However, the issue in creating a preparative mD-LC system is that the higher the dimensionality, the more complicated the system configuration. Thus, we presented a new configuration of preparative mD-LC using one set of LC modules and trapping array-based multiple heart-cut interfaces. A preparative two-dimensional liquid chromatography (2D-LC) separation of herbal medicine formulation produced 40 compounds with a purity of >90%. During the separation process, the interface stores the fractions and allocates positions for the fractions from a different dimension; LC draws the fraction from the interface, makes nD separation, and sends isolated fractions to the interface. By repeating this process, we achieved variable dimensionality of LC separations. We also presented a preparative 3D-LC separation of herbal medicines to validate the principle of "less configuration and more dimensionality". Thus, we can explore the higher dimensional preparative separations. The developed preparative mD-LC displayed exceptional power in the isolation of various compounds and has great potential in the application of natural products.