Efficient Large-Area (81 cm2) Ternary Copper Halides Light-Emitting Diodes with External Quantum Efficiency Exceeding 13% via Host-Guest Strategy.

Ternary copper (Cu) halides are promising candidates for replacing toxic lead halides in the field of perovskite light-emitting diodes (LEDs) toward practical applications. However, the electroluminescent performance of Cu halide-based LEDs remains a great challenge due to the presence of serious nonradiative recombination and inefficient charge transport in Cu halide emitters. Here, the rational design of host-guest [dppb]2Cu2I2 (dppb denotes 1,2-bis[diphenylphosphino]benzene) emitters and its utility in fabricating efficient Cu halide-based green LEDs that show a high external quantum efficiency (EQE) of 13.39% are reported. The host-guest [dppb]2Cu2I2 emitters with mCP (1,3-bis(N-carbazolyl)benzene) host demonstrate a significant improvement of carrier radiative recombination efficiency, with the photoluminescence quantum yield increased by nearly ten times, which is rooted in the efficient energy transfer and type-I energy level alignment between [dppb]2Cu2I2 and mCP. Moreover, the charge-transporting mCP host can raise the carrier mobility of [dppb]2Cu2I2 films, thereby enhancing the charge transport and recombination. More importantly, this strategy enables a large-area prototype LED with a record-breaking area up to 81 cm2, along with a decent EQE of 10.02% and uniform luminance. It is believed these results represent an encouraging stepping stone to bring Cu halide-based LEDs from the laboratory toward commercial lighting and display panels.

Antibacterial polyurethane foams with quaternized-chitosan as a chain extender for nasal packing and hemostasis.

Endoscopic surgery is an effective and common clinical practice for chronic sinusitis. Nasal packing materials are applied in nasal surgery to prevent hemorrhage and promote wound healing. In this study, a degradable polyurethane foam dressing is successfully developed as a promising nasal packing material with good biocompatibility and antibacterial capability. Specifically, quaternized chitosan (QCS) serves as the crosslinker instead of polyols to offer polyurethane foam (PUF-QCS) antibacterial capability. The PUF-QCS2.0 % (with 2.0 wt% QCS) exhibits satisfactory liquid absorption capacity (19.4 g/g), high compressive strengths at both wet (14.5 kPa) and dry states (7.7 kPa), and a good degradation rate (8.3 %) within 7 days. Meanwhile, PUF-QCS2.0 % retains long-term antibacterial activity for 7 days and kills 97.3 % of S. aureus and 91.8 % of E. coli within 6 hours in antibacterial testing. Furthermore, PUF-QCS2.0 % demonstrates a positive hemostatic response in the rabbit nasal septum mucosa trauma model by reducing hemostatic time over 50.0 % and decreasing blood loss up to 76.1 % compared to the commercial PVA nasal packing sponge. Importantly, PUF-QCS also exhibits a significant antibacterial activity in nasal cavity. This nasal packing material has advantages in post-surgery bleeding control and infection prevention. STATEMENT OF SIGNIFICANCE: The performance of a nasal packing sponge requires good mechanical properties, fast and high liquid absorption rate, effective degradability and strong antibacterial activity. These features are helpful for improving the postoperative recovery and patient healing. However, integrating these into a single polyurethane foam is a challenge. In this study, quaternized chitosan (QCS) is synthesized and used as a chain extender and antibacterial agent in preparing a degradable polyurethane foam (PUF-QCS) dressing. PUF-QCS undergoes partial degradation and exhibits effective broad-spectrum antibacterial activity in 7 days. The reduction of postoperative bleeding and infection observed in the animal experiment further demonstrates that the PUF-QCS developed here outperforms the existing commercial nasal packing materials.

Preexisting Diabetes and Breast Cancer Treatment Among Low-Income Women.

IMPORTANCE: Diabetes is associated with poorer prognosis of patients with breast cancer. The association between diabetes and adjuvant therapies for breast cancer remains uncertain. OBJECTIVE: To comprehensively examine the associations of preexisting diabetes with radiotherapy, chemotherapy, and endocrine therapy in low-income women with breast cancer. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study included women younger than 65 years diagnosed with nonmetastatic breast cancer from 2007 through 2015, followed up through 2016, continuously enrolled in Medicaid, and identified from the linked Missouri Cancer Registry and Medicaid claims data set. Data were analyzed from January 2022 to October 2023. EXPOSURE: Preexisting diabetes. MAIN OUTCOMES AND MEASURES: Logistic regression was used to estimate odds ratios (ORs) of utilization (yes/no), timely initiation (≤90 days postsurgery), and completion of radiotherapy and chemotherapy, as well as adherence (medication possession ratio ≥80%) and persistence (<90-consecutive day gap) of endocrine therapy in the first year of treatment for women with diabetes compared with women without diabetes. Analyses were adjusted for sociodemographic and tumor factors. RESULTS: Among 3704 women undergoing definitive surgery, the mean (SD) age was 51.4 (8.6) years, 1038 (28.1%) were non-Hispanic Black, 2598 (70.1%) were non-Hispanic White, 765 (20.7%) had a diabetes history, 2369 (64.0%) received radiotherapy, 2237 (60.4%) had chemotherapy, and 2505 (67.6%) took endocrine therapy. Compared with women without diabetes, women with diabetes were less likely to utilize radiotherapy (OR, 0.67; 95% CI, 0.53-0.86), receive chemotherapy (OR, 0.67; 95% CI, 0.48-0.93), complete chemotherapy (OR, 0.71; 95% CI, 0.50-0.99), and be adherent to endocrine therapy (OR, 0.71; 95% CI, 0.56-0.91). There were no significant associations of diabetes with utilization (OR, 0.95; 95% CI, 0.71-1.28) and persistence (OR, 1.09; 95% CI, 0.88-1.36) of endocrine therapy, timely initiation of radiotherapy (OR, 1.09; 95% CI, 0.86-1.38) and chemotherapy (OR, 1.09; 95% CI, 0.77-1.55), or completion of radiotherapy (OR, 1.25; 95% CI, 0.91-1.71). CONCLUSIONS AND RELEVANCE: In this cohort study, preexisting diabetes was associated with subpar adjuvant therapies for breast cancer among low-income women. Improving diabetes management during cancer treatment is particularly important for low-income women with breast cancer who may have been disproportionately affected by diabetes and are likely to experience disparities in cancer treatment and outcomes.

Prolonged intermittent theta burst stimulation for post-stroke aphasia: protocol of a randomized, double-blinded, sham-controlled trial.

Background: Post-stroke aphasia (PSA) is one of the most devastating symptoms after stroke, yet limited treatment options are available. Prolonged intermittent theta burst stimulation (piTBS) is a promising therapy for PSA. However, its efficacy remains unclear. Therefore, we aim to investigate the efficacy of piTBS over the left supplementary motor area (SMA) in improving language function for PSA patients and further explore the mechanism of language recovery. Methods: This is a randomized, double-blinded, sham-controlled trial. A total of 30 PSA patients will be randomly allocated to receive either piTBS stimulation or sham stimulation for 15 sessions over a period of 3 weeks. The primary outcome is the Western Aphasia Battery Revised (WAB-R) changes after treatment. The secondary outcomes include The Stroke and Aphasia Quality of Life Scale (SAQOL-39 g), resting-state electroencephalogram (resting-state EEG), Event-related potentials (ERP), brain derived neurotrophic factor (BDNF). These outcome measures are assessed before treatment, after treatment, and at 4-weeks follow up. This study was registered in Chinese Clinical Trial Registry (No. ChiCTR23000203238). Discussion: This study protocol is promising for improving language in PSA patients. Resting-state EEG, ERP, and blood examination can be used to explore the neural mechanisms of PSA treatment with piTBS. Clinical trial registration: https://www.chictr.org.cn/index.html, ChiCTR2300074533.

Camrelizumab plus famitinib in previously chemo-immunotherapy treated patients with advanced NSCLC: results from an open-label multicenter phase 2 basket study.

BACKGROUND: The combination of immune checkpoint inhibitors and antiangiogenic agents has been effective in treating multiple cancers. This was further explored in an open-label, multicenter phase 2 basket study (NCT04346381), which evaluated the antitumor activity and safety of camrelizumab (an anti-PD-1 antibody) plus famitinib (a receptor tyrosine kinase inhibitor) in patients with advanced solid tumors. We herein report the findings from the cohort of advanced NSCLC patients who progressed after treatment with platinum-doublet chemotherapy and immunotherapy. METHODS: Eligible patients were enrolled and treated with camrelizumab (200 mg once every 3 weeks via intravenous infusion) and oral famitinib (20 mg once daily). The primary endpoint was the objective response rate (ORR). Secondary endpoints included the disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Forty patients were enrolled in this cohort, with a median follow-up duration of 11.5 months. Three patients (7.5%) achieved a partial response, and 29 patients (72.5%) achieved stable disease. The ORR and DCR with this combination regimen were 7.5% (95% CI, 1.6-20.4) and 80.0% (95% CI, 64.4-90.9), respectively. The median DoR was 12.1 months (95% CI, 10.3-not reached). The median PFS was 5.4 months (95% CI, 4.1-7.5), and the median OS was 12.1 months (95% CI, 9.1-16.7). The estimated 12-month OS rate was 51.5% (95% CI, 34.9-65.9). The most frequent grade 3 or higher treatment-related adverse events occurring in more than 5% of patients included hypertension (27.5%), palmar-plantar erythrodysesthesia syndrome (10%), decreased neutrophil count (10%), and proteinuria (7.5%). CONCLUSION: Camrelizumab plus famitinib demonstrated favorable benefits in PFS and OS, along with manageable safety profiles, in patients with advanced NSCLC who progressed after platinum-doublet chemotherapy and immunotherapy. This finding warrants further exploration.

MICAL-L2, as an estrogen-responsive gene, is involved in ER-positive breast cancer cell progression and tamoxifen sensitivity via the AKT/mTOR pathway.

Endocrine treatment, particularly tamoxifen, has shown significant improvement in the prognosis of patients with estrogen receptor-positive (ER-positive) breast cancer. However, the clinical utility of this treatment is often hindered by the development of endocrine resistance. Therefore, a comprehensive understanding of the underlying mechanisms driving ER-positive breast cancer carcinogenesis and endocrine resistance is crucial to overcome this clinical challenge. In this study, we investigated the expression of MICAL-L2 in ER-positive breast cancer and its impact on patient prognosis. We observed a significant upregulation of MICAL-L2 expression in ER-positive breast cancer, which correlated with a poorer prognosis in these patients. Furthermore, we found that estrogen-ERß signaling promoted the expression of MICAL-L2. Functionally, our study demonstrated that MICAL-L2 not only played an oncogenic role in ER-positive breast cancer tumorigenesis but also influenced the sensitivity of ER-positive breast cancer cells to tamoxifen. Mechanistically, as an estrogen-responsive gene, MICAL-L2 facilitated the activation of the AKT/mTOR signaling pathway in ER-positive breast cancer cells. Collectively, our findings suggest that MICAL-L2 could serve as a potential prognostic marker for ER-positive breast cancer and represent a promising molecular target for improving endocrine treatment and developing therapeutic approaches for this subtype of breast cancer.

Discharge within 24 h, transvaginal natural orifice transluminal endoscopic surgery- more suitable for ambulatory surgery in gynecology procedures: a retrospective study.

BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) is an achievement in the field of minimally invasive surgery. However, the vantage point of vaginal natural orifice transluminal endoscopic surgery (vNOTES) in gynecologicalprocedures remains unclear. The main purpose of this study was to compare vNOTES with laparo-endoscopic single-site surgery, and to determine which procedure is more suitable for ambulatory surgery in gynecologic procedures. METHODS: This retrospective observational study was conducted at the Department of Gynecology, Chengdu Women's and Children's Central Hospital. The 207 enrolled patients had accepted vNOTES and laparo-endoscopic single-site surgery in gynecology procedures from February 2021 to March 2022. Surgically relevant information regarding patients who underwent ambulatory surgery was collected, and 64 females underwent vNOTES. RESULTS: Multiple outcomes were analyzed in 207 patients. The Wilcoxon Rank-Sum test showed that there were statistically significant differences between the vNOTES and laparo-endoscopic single-site surgery groups in terms of postoperative pain score (0 vs. 1 scores, p = 0.026), duration of anesthesia (90 vs. 101 min, p = 0.025), surgery time (65 vs. 80 min, p = 0.015), estimated blood loss (20 vs. 40 mL, p < 0.001), and intestinal exhaustion time (12.20 vs. 17.14 h, p < 0.001). Treatment with vNOTES resulted in convenience, both with respect to time savings and hemorrhage volume in surgery and with respect to the quality of the prognosis. CONCLUSION: These comprehensive data reveal the capacity of vNOTES to increase surgical efficiency. vNOTES in gynecological procedures may demonstrate sufficient feasibility and provide a new medical strategy compared with laparo-endoscopic single-site surgery for ambulatory surgery in gynecological procedures.

Shared xerophytic genes and their re-use in local adaptation to aridity in the desert plant Gymnocarpos przewalskii.

In order to thrive and survive, plant species need to combine stability in the long term and rapid response to environmental challenges in the short term. The former would be reflected by parallel or convergent adaptation across species, and the latter by pronounced local adaptation among populations of the same species. In the present study, we generated a high-quality genome and re-sequenced 177 individuals for Gymnocarpos przewalskii, an important desert plant species from North-West China, to detect local adaptation. We first focus on ancient adaptation to aridity at the molecular level by comparing the genomic data of 15 species that vary in their ability to withstand aridity. We found that a total of 118 genes were shared across xerophytic species but absent from non-xerophytic species. Of the 65 found in G. przewalskii, 63 were under purifying selection and two under positive selection. We then focused on local adaptation. Up to 20% of the G. przewalskii genome showed signatures of local adaptation to aridity during population divergence. Thirteen of the selected shared xerophytic genes were reused in local adaptation after population differentiation. Hence, only about 20% of the genes shared and specific to xerophytic species and associated with adaptation to aridity were later recruited for local adaptation in G. przewalskii.

Brain Network Characterization of Preterm Infants With Bronchopulmonary Dysplasia.

BACKGROUND: Bronchopulmonary dysplasia (BPD) affects the microstructure of white matter in preterm infants, but its influence on the changes of the brain structural network has not been elaborated. This study aims to investigate the connectivity characteristics of the brain structural network of BPD by using diffusion tensor imaging. METHODS: Thirty-three infants with BPD and 26 infants without BPD were enrolled in this study. Brain structural networks were constructed utilizing automated anatomic labeling mapping by tracing the fibers between each pair of regions in individual space. We calculated network metrics such as global efficiency, local efficiency, clustering coefficients, characteristic path length, and small-worldness. Then we compared the network metrics of these infants with those of 57 healthy term infants of comparable postmenstrual age at magnetic resonance imaging scan. Finally, network-based statistics was used to analyze the differences in brain network connectivity between the groups with and without BPD. RESULTS: Preterm infants with BPD had higher local efficiency and clustering coefficient, lower global efficiency, and longer characteristic path length. Also, preterm infants with BPD had decreased strength of limbic connections mainly in four brain regions: the left lingual gyrus, the left calcarine fissure and surrounding cortex, the right parahippocampal gyrus, and the left precuneus. CONCLUSIONS: Our findings suggest that preterm infants with BPD have lower network integration and higher segregation at term-equivalent age, which may reflect a compensatory mechanism. In addition, BPD affects brain regions involved in visual as well as cognitive functions; these findings provide a new approach to diagnose potential brain damage in preterm infants with BPD.

Properties of modified chitosan-based films and coatings and their application in the preservation of edible mushrooms: A review.

Edible mushrooms are prone to deteriorate during storage. A Single chitosan film or coating has limitations in preservation. Therefore, this article focused on the improvement of modified chitosan-based films and coatings on properties related to storage quality of edible mushrooms (e.g.: safety, barrier, mechanical, antioxidant and antibacterial properties). Besides, the application of chitosan-based materials in the preservation of mushrooms was also discussed. The modified chitosan film and coating can slow down the respiration of mushrooms, inhibit the growth of microorganisms, protect antioxidant compositions, and regulate the activity of related enzymes, thus improving the quality and prolonging the shelf life of mushrooms. Meanwhile, the added ingredients improve the water and gas barrier properties of chitosan through volume and group occupation, and reduce the light transmittance of chitosan through light transmission, scattering and absorption. Essential oils and polyphenolic compounds had a better enhancement of antioxidant and antimicrobial properties of chitosan.

Myasthenia gravis with tongue muscle atrophy: A case series.

Here, we presented 6 patients who were admitted to our institution and diagnosed as myasthenia gravis (MG) with tongue muscle atrophy. All these 6 patients developed symptoms of bulbar muscle weakness in acetylcholine receptor antibodies positive MG (AChR-MG) (3/6), muscle-specific receptor tyrosine kinase antibodies positive MG (MuSK-MG) (1/6), and sero-negative MG (2/6). Most of patients had "triple-furrowed" tongue except for patient 2 with irregular atrophy of tongue muscle. Tongue muscle atrophy occurs in patients with MuSK-MG, AChR-MG, and sero-negative MG. Atrophied tongue muscles of five patients with MG were reversible after immunotherapy.

A laser-Engraved Wearable Electrochemical Sensing Patch for Heat Stress Precise Individual Management of Horse.

In point-of-care diagnostics, the continuous monitoring of sweat constituents provides a window into individual's physiological state. For species like horses, with abundant sweat glands, sweat composition can serve as an early health indicator. Considering the salience of such metrics in the domain of high-value animal breeding, a sophisticated wearable sensor patch tailored is introduced for the dynamic assessment of equine sweat, offering insights into pH, potassium ion (K+), and temperature profiles during episodes of heat stress and under normal physiological conditions. The device integrates a laser-engraved graphene (LEG) sensing electrode array, a non-invasive iontophoretic module for stimulated sweat secretion, an adaptable signal processing unit, and an embedded wireless communication framework. Profiting from an admirable Truth Table capable of logical evaluation, the integrated system enabled the early and timely assessment for heat stress, with high accuracy, stability, and reproducibility. The sensor patch has been calibrated to align with the unique dermal and physiological contours of equine anatomy, thereby augmenting its applicability in practical settings. This real-time analysis tool for equine perspiration stands to revolutionize personalized health management approaches for high-value animals, marking a significant stride in the integration of smart technologies within the agricultural sector.

The resistance patterns and molecular characteristics of ESBL/AmpC-producing Escherichia coli from captive panda ecosystem in China.

Escherichia coli (E. coli) plays an important ecological role, and is a useful bioindicator to recognize the evolution of resistance in human, animal and environment. Recently, extended-spectrum ß-lactamases (ESBL) producing E.coli has posed a threat to public health. Generally, captive healthy giant pandas are not exposed to antibiotics; however, they still acquire antimicrobial resistant bacteria. In order to understand whether there is an exchange of resistance genes within the ecosystems of captive giant pandas, this study explored resistance characteristics of 330 commensal E. coli isolates from feces of giant pandas, the surroundings, and breeders. Isolates from different sources showed similar resistance phenotype, and ESBL/AmpC-producing isolates showed more profound resistance to antibiotics than non-ESBL/AmpC-producing isolates (P<0.05). Furthermore, the occurrence of broad-spectrum ß-lactamase related resistance genes and colistin resistance genes was detected, and isolates phylogenetic typing and multilocus sequence typing (MLST) were applied in this study. Seven different ß-lactamase resistance genes (blaCTX-M-55, blaCTX-M-15, blaCTX-M-27, blaCTX-M-65, blaTEM-1, blaOXA-1 and blaCMY) and mcr-1 were found in 68 ESBL/AmpC-producing isolates. blaCTX-M-55 (48.53 %) was found the most predominant resistance genes, followed by blaTEM-1 (19.12 %) and blaCTX-M-27 (16.18 %). Nonetheless, blaCTX-M-55 was commonly detected in the isolates from giant pandas (63.16 %), the surroundings (43.48 %), and breeders (33.33 %). However, there were no carbapenemase genes detected in this study. mcr-1 was harbored in only one isolate from giant panda. Forty-five tansconjugants were successfully obtained in the conjugation experiments. The presence of antimicrobial resistance and related resistance genes tested were observed in the transconjugants. The results indicated that 52.63 % of the isolates from giant panda 73.91 % of the isolates from surroundings, and 100 % of the isolates from breeders were phylogroup A. Total of 27 sequence types (ST) were recognized from the isolate by MLST and found that ST48 (19/68; 27.94 %) was the predominant ST type, especially in the isolates from giant pandas and the surroundings. In conclusion, commensal ESBL/AmpC-producing E. coli becomes a reservoir of ESBL resistance genes, which is a potential threaten to health of giant pandas. The interaction between giant pandas, surroundings and breeders contribute to development of resistant phenotypes and genotypes which might transfer across species or the surroundings easily; hence, strict monitoring based on a "One Health" approach is recommended.

Resonant exchange of Chiral Majorana Fermions modulated by two parallel quantum dots.

Resonant exchange of the chiral Majorana fermions (MFs) that is coupled to two parallel Majorana zero modes (MZMs) or two parallel quantum dots (QDs) is investigated. We find that, in the two QDs coupling case, the resonant exchange for the chiral MFs is analogous to that in the MZM coupling case. We further propose a circuit based on topological superconductor (TSC), which is formed by the proximity coupling of a quantum anomalous Hall insulator (QAHI) and a s-wave superconductor, to observe the resonant exchange of chiral MFs pairs. The numerical calculations show that the resonant transmission of the chiral MFs can be adjusted by varying the coupling parameters. It is particularly noteworthy that, by only modulating the coupling strength between the two QDs, the resonant exchange may be switched on or off. By adding another MZM, the non-Abelian braidinglike operation can be realized. Therefore, our design scheme may provide another way for non-Abelian braiding operation of MFs and the findings may have potential application value in the realization of topological quantum computers.

Safety of Repeated Low-level Red-Light Therapy for Children with Myopia.

BACKGROUD: To investigate the safety of repetitive low-level red-light therapy (RLRLT) in children with myopia. METHODS: Children with myopia were assigned to the RLRL and control groups. Axial length (AL) and spherical equivalent refraction (SER) were followed up at 3-, 6-, and 12-month. To evaluate the safety of RLRLT, at 6 and 12 months in the RLRL group, multifocal electroretinography (mfERG) and contrast sensitivity were recorded. Furthermore, optical coherence tomography was used to measure the relative reflectance of the ellipsoid zone (rEZR), photoreceptor outer segment (rPOSR), and retinal pigment epithelium (rRPER). RESULTS: A total of 108 children completed the trial (55 in the RLRL group and 53 in the control group). After 3, 6, and 12 months, axial length (AL) was shorter and SER less myopic in the RLRL group than in the control group. Regarding the safety of the RLRLT, the response density and amplitude of the P1 wave of the first ring of the mfERG increased significantly at 6 months (P =0.001 and P =0.017, respectively). At 6 and 12 months, contrast sensitivity at the high spatial frequency increased. Moreover, the rEZR increased significantly at 6 months (P =0.029), the rPOSR increased significantly at 6 and 12 months (both P <0.001), and the increase in rPOSR was greater with greater AL regression. CONCLUSIONS: Based on retinal function follow-up, RLRLT was safe within 12 months. However, rEZR and rPOSR increased, the effects of this phenomenon requires further observation.

Disseminated Talaromyces marneffei infection initially presenting as cutaneous and subcutaneous lesion in an HIV-Negative renal transplant recipient: a case report and literature review.

BACKGROUND: The incidence of Talaromyces marneffei (T. marneffei) infection has increased in recent years with the development of organ transplantation and the widespread use of immunosuppressive agents. However, the lack of clinical suspicion leading to delay or misdiagnosis is an important reason for the high mortality rate in non-human immunodeficiency virus (HIV) and non-endemic population. Herein, we report a case of disseminated T. marneffei infection in a non-HIV and non-endemic recipient after renal transplant, who initially presented with skin rashes and subcutaneous nodules and developed gastrointestinal bleeding. CASE PRESENTATION: We describe a 54-year-old renal transplantation recipient presented with scattered rashes, subcutaneous nodules and ulcerations on the head, face, abdomen, and right upper limb. The HIV antibody test was negative. The patient had no obvious symptoms such as fever, cough, etc. Histopathological result of the skin lesion sites showed chronic suppurative inflammation with a large number of fungal spores. Subsequent fungal culture suggested T. marneffei infection. Amphotericin B deoxycholate was given for antifungal treatment, and there was no deterioration in the parameters of liver and kidney function. Unfortunately, the patient was soon diagnosed with gastrointestinal bleeding, gastrointestinal perforation and acute peritonitis. Then he rapidly developed multiple organ dysfunction syndrome and abandoned treatment. CONCLUSIONS: The risk of fatal gastrointestinal bleeding can be significantly increased in kidney transplant patients with T. marneffei infection because of the long-term side effects of post-transplant medications. Strengthening clinical awareness and using mNGS or mass spectrometry technologies to improve the detection rate and early diagnosis of T. marneffei are crucial for clinical treatment in non-HIV and non-endemic population.

Specific biomarkers and neurons distribution of different brain regions in largemouth bass (Micropterus salmoides).

The brain regulates multiple physiological processes in fish. Despite this, knowledge about the basic structure and function of distinct brain regions in non-model fish species remains limited due to their diversity and the scarcity of common biomarkers. In the present study, four major brain parts, the telencephalon, diencephalon, mesencephalon and rhombencephalon, were isolated in largemouth bass, Micropterus salmoides. Within these parts, nine brain regions and 74 nuclei were further identified through morphological and cytoarchitectonic analysis. Transcriptome analysis revealed a total of 7153 region-highly expressed genes and 176 region-specifically expressed genes. Genes related to growth, reproduction, emotion, learning, and memory were significantly overexpressed in the olfactory bulb and telencephalon (OBT). Feeding and stress-related genes were in the hypothalamus (Hy). Visual system-related genes were predominantly enriched in the optic tectum (OT), while vision and hearing-related genes were widely expressed in the cerebellum (Ce) region. Sensory input and motor output-related genes were in the medulla oblongata (Mo). Osmoregulation, stress response, sleep/wake cycles, and reproduction-related genes were highly expressed in the remaining brain (RB). Three candidate marker genes were further identified for each brain regions, such as neuropeptide FF (npff) for OBT, pro-melanin-concentrating hormone (pmch) for Hy, vesicular inhibitory amino acid transporter (viaat) for OT, excitatory amino acid transporter 1 (eaat1) for Ce, peripherin (prph) for Mo, and isotocin neurophysin (itnp) for RB. Additionally, the distribution of seven neurotransmitter-type neurons and five types of non-neuronal cells across different brain regions were analyzed by examining the expression of their marker genes. Notably, marker genes for glutamatergic and GABAergic neurons showed the highest expression levels across all brain regions. Similarly, the marker gene for radial astrocytes exhibited high expression compared to other markers, while those for microglia were the least expressed. Overall, our results provide a comprehensive overview of the structural and functional characteristics of distinct brain regions in the largemouth bass, which offers a valuable resource for understanding the role of central nervous system in regulating physiological processes in teleost.

Variable patterns of retrotransposition in different HeLa strains provide mechanistic insights into SINE RNA mobilization processes.

Alu elements are non-autonomous Short INterspersed Elements (SINEs) derived from the 7SL RNA gene that are present at over one million copies in human genomic DNA. Alu mobilizes by a mechanism known as retrotransposition, which requires the Long INterspersed Element-1 (LINE-1 or L1) ORF2 -encoded protein (ORF2p). Here, we demonstrate that HeLa strains differ in their capacity to support Alu retrotransposition. Human Alu elements retrotranspose efficiently in HeLa-HA and HeLa-CCL2 ( Alu -permissive) strains, but not in HeLa-JVM or HeLa-H1 ( Alu -nonpermissive) strains. A similar pattern of retrotransposition was observed for other 7SL RNA -derived SINEs and tRNA -derived SINEs. In contrast, mammalian LINE-1s, a zebrafish LINE, a human SINE-VNTR - Alu ( SVA ) element, and an L1 ORF1 -containing messenger RNA can retrotranspose in all four HeLa strains. Using an in vitro reverse transcriptase-based assay, we show that Alu RNAs associate with ORF2p and are converted into cDNAs in both Alu -permissive and Alu -nonpermissive HeLa strains, suggesting that 7SL - and tRNA -derived SINE RNAs use strategies to 'hijack' L1 ORF2p that are distinct from those used by SVA elements and ORF1 -containing mRNAs. These data further suggest ORF2p associates with the Alu RNA poly(A) tract in both Alu -permissive and Alu -nonpermissive HeLa strains, but that Alu retrotransposition is blocked after this critical step in Alu -nonpermissive HeLa strains.

Gene mutation profiling in microsatellite instability colorectal cancer and its association with the efficacy of immunotherapy: A retrospective study.

BACKGROUND: Microsatellite instability-high (MSI-H) colorectal cancer (CRC) is known for its heightened responsiveness to immunotherapy. However, establishing robust predictive markers for immunotherapy efficacy remains imperative. This retrospective study aimed to elucidate the genetic landscape of MSI-H CRC and correlate these genetic alterations with immunotherapy outcomes in a cohort of 121 patients. METHODS: We analyzed clinical and molecular data from 121 patients with MSI-H CRC. We conducted a thorough genetic analysis of MSI-H CRC patients, with a specific emphasis on the APC, TP53, RAS, and MMR genes. We further analyzed the relationship between gene mutations and immunotherapy efficacy. The primary endpoints analyzed were objective response rate (ORR) and progression-free survival (PFS). All statistical analysis was conducted using SPSS26.0 and R 4.2.0 software. RESULTS: Our findings underscored the complexity of the genetic landscape in MSI-H CRC, shedding light on the intricate interplay of these genes in CRC development. Notably, mutations in MMR genes exhibited a distinctive pattern, providing insights into the underlying mechanisms of MSI-H. Furthermore, our results revealed correlations between specific genetic alterations and immunotherapy outcomes, with a particular focus on treatment response rates and progression-free survival. CONCLUSION: This study represents a significant step toward unraveling the genetic nuances of MSI-H CRC. The distinctive pattern of MMR gene mutations not only adds depth to our understanding of MSI-H CRC but also hints at potential avenues for targeted therapies. This research sets the stage for future investigations aimed at refining therapeutic strategies and improving outcomes for patients with MSI-H CRC.