Association between genetically proxied glucosamine and risk of cancer and non-neoplastic disease: A Mendelian randomization study.

Introduction: Observational investigations have examined the impact of glucosamine use on the risk of cancer and non-neoplastic diseases. However, the findings from these studies face limitations arising from confounding variables, reverse causation, and conflicting reports. Consequently, the establishment of a causal relationship between habitual glucosamine consumption and the risk of cancer and non-neoplastic diseases necessitates further investigation. Methods: For Mendelian randomization (MR) investigation, we opted to employ single-nucleotide polymorphisms (SNPs) as instruments that exhibit robust associations with habitual glucosamine consumption. We obtained the corresponding effect estimates of these SNPs on the risk of cancer and non-neoplastic diseases by extracting summary data for genetic instruments linked to 49 varied cancer types amounting to 378,284 cases and 533,969 controls, as well as 20 non-neoplastic diseases encompassing 292,270 cases and 842,829 controls. Apart from the primary analysis utilizing inverse-variance weighted MR, we conducted two supplementary approaches to account for potential pleiotropy (MR-Egger and weighted median) and assessed their respective MR estimates. Furthermore, the results of the leave-one-out analysis revealed that there were no outlying instruments. Results: Our results suggest divergence from accepted biological understanding, suggesting that genetically predicted glucosamine utilization may be linked to an increased vulnerability to specific illnesses, as evidenced by increased odds ratios and confidence intervals (95% CI) for diseases, such as malignant neoplasm of the eye and adnexa (2.47 [1.34-4.55]), benign neoplasm of the liver/bile ducts (2.12 [1.32-3.43]), benign neoplasm of the larynx (2.01 [1.36-2.96]), melanoma (1.74 [1.17-2.59]), follicular lymphoma (1.50 [1.06-2.11]), autoimmune thyroiditis (2.47 [1.49-4.08]), and autoimmune hyperthyroidism (1.93 [1.17-3.18]). In contrast to prior observational research, our genetic investigations demonstrate a positive correlation between habitual glucosamine consumption and an elevated risk of sigmoid colon cancer, lung adenocarcinoma, and benign neoplasm of the thyroid gland. Conclusion: Casting doubt on the purported purely beneficial association between glucosamine ingestion and prevention of neoplastic and non-neoplastic diseases, habitual glucosamine ingestion exhibits dichotomous effects on disease outcomes. Endorsing the habitual consumption of glucosamine as a preventative measure against neoplastic and non-neoplastic diseases cannot be supported.

Speech Perception and Quality-of-Life Outcomes in Mandarin-Speaking Postlingual Deaf Adults With Cochlear Implant: Any Difference With the Intonation Language Users?

OBJECTIVE: To evaluate the effects of related factors on long-term speech perception and quality-of-life (QoL) outcomes in postlingual deaf Mandarin-speaking adult cochlear implant (CI) recipients and to assess any differences between tone language and other intonation language CI adult users. STUDY DESIGN: Retrospective cases review. SETTING: Tertiary referral center. PATIENTS: Forty-five adult CI recipients (48 implanted ears). MAIN OUTCOME MEASURES: Post-CI outcomes were evaluated after follow-ups of more than 24 months using speech perception tests and QoL questionnaires. We analyzed the related factors affecting CI outcomes. RESULTS: A shorter duration of profound deafness was predictive factors for better post-CI speech perception. Earlier implantation and better performance of vowel scores were predictive of better subjective improvements in social and emotional life. Post-CI vowel scores of over 56% indicated promising improvements in QoL. CONCLUSION: Shorter duration of deafness could have better post-CI speech perception. Post-CI vowel scores instead of monosyllable words have the more potential to predict the QoL in Mandarin-speaking adult CI recipients.

A serine carboxypeptidase-like acyltransferase catalyzes consecutive four-step reactions of hydrolyzable tannin biosynthesis in Camellia oleifera.

Hydrolyzable tannins (HTs), a class of polyphenolic compounds found in dicotyledonous plants, are widely used in food and pharmaceutical industries because of their beneficial effects on human health. Although the biosynthesis of simple HTs has been verified at the enzymatic level, relevant genes have not yet been identified. Here, based on the parent ion-fragment ion pairs in the feature fragment data obtained using UPLC-Q-TOF-/MS/MS, galloyl phenolic compounds in the leaves of Camellia sinensis and C. oleifera were analyzed qualitatively and quantitatively. Correlation analysis between the transcript abundance of serine carboxypeptidase-like acyltransferases (SCPL-ATs) and the peak area of galloyl products in Camellia species showed that SCPL3 expression was highly correlated with HT biosynthesis. Enzymatic verification of the recombinant protein showed that CoSCPL3 from C. oleifera catalyzed the four consecutive steps involved in the conversion of digalloylglucose to pentagalloylglucose. We also identified the residues affecting the enzymatic activity of CoSCPL3 and determined that SCPL-AT catalyzes the synthesis of galloyl glycosides. The findings of this study provide a target gene for germplasm innovation of important cash crops that are rich in HTs, such as C. oleifera, strawberry, and walnut.

The effect of refined psychological pain nursing combined with IMB nursing on the pain, sleep and quality of life of patients after cervical cancer surgery.

To explore the effect of refined psychological pain nursing combined with information-motivation-behavioral (IMB) care model on the pain, sleep and quality of life of patients after cervical cancer surgery, so as to provide reference and basis for the nursing of patients after cervical cancer surgery. The clinical data of 798 postoperative cervical cancer patients who were nursing in our hospital from January 2018 to December 2022 were included in this retrospective study and divided into the control group (n = 382) and observation group (n = 416) according to the different care methods. The control group used refined psychological pain nursing, and on this basis, the observation group used IMB nursing to observe and compare the differences in pain, sleep and quality of life between the 2 groups. There was no significant difference in pain between the 2 groups before nursing (P > .05). After nursing, the pain of both groups was significantly improved. The scores of NRS, VAS, and PSEQ of the observation group were significantly better than those of the control group (P < .001). After nursing, the quality of life scores such as emotion, cognition, society, and overall health were significantly higher in the observation group than those of the control group, while physical, fatigue, nausea, vomiting, and pain were significantly lower than those of the control group (P < .05). The negative emotion score of the observation group was significantly lower than that of the control group (P < .001). The residual urine volume and urinary tract infection rate of the observation group were significantly lower than those of the control group (P < .05). The bladder function was significantly better than that of the control group (P < .05). The analgesic effect of refined psychological pain nursing combined with IMB nursing on patients after cervical cancer surgery is better than that of refined psychological pain nursing alone, which can promote pain recovery and further improve the quality of life and sleep quality of patients.

Bilateral cochlear implants in a MELAS patient.

BACKGROUND: Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a maternally inherited mitochondrial disease that affects various systems in the body, particularly the brain, nervous system, and muscles. Among these systems, sensorineural hearing loss is a common additional symptom. METHODS: A 42-year-old female patient with MELAS who experienced bilateral profound deafness and underwent bilateral sequential cochlear implantation (CIs). Speech recognition and subjective outcomes were evaluated. RESULTS: Following the first CI follow-up, the patient exhibited improved speech recognition ability and decided to undergo the implantation of the second ear just two months after the initial CI surgery. The second CI also demonstrated enhanced speech recognition ability. Subjective outcomes were satisfactory for bilateral CIs. CONCLUSIONS: MELAS patients receiving bilateral CIs can attain satisfactory post-CI speech recognition, spatial hearing, and sound qualities.

The fabrication of silicon/dual-network carbon nanofibers/carbon nanotubes as free-standing anodes for lithium-ion batteries.

Silicon, known for its high theoretical capacity and abundant resources, is regarded as one of the most promising anode materials for lithium-ion batteries (LIBs). However, the application of silicon anode materials is limited by huge expansion and poor electricity of silicon. Herein, a novel free-standing Si/C anode (noted as Si/CNFs/CNTs) is synthesized by combining electrospinning and in situ chemical vapor deposition, in which Si nanoparticles are composited with a conducting dual-network composed of carbon nanofibers (CNFs) and in situ deposited carbon nanotubes (CNTs). In situ deposited CNTs surround the surface of CNFs to form an elastic buffer layer on the surface of Si attached to CNFs, which ensures structural integrity. CNTs with excellent conductivity and a large specific surface area shorten Li+ transport pathways. Therefore, Si/CNFs/CNTs exhibits stable cycling performance and maintains a capacity of 639.9 mA h g-1 and a capacity retention rate of 69.9% after 100 cycles at a current density of 0.1 A g-1. This work provides a promising approach for the structural modification of self-supporting Si/C electrodes.

Alterations of lower respiratory tract microbiome and short-chain fatty acids in different segments in lung cancer: a multiomics analysis.

Introduction: The lower respiratory tract microbiome is widely studied to pinpoint microbial dysbiosis of diversity or abundance that is linked to a number of chronic respiratory illnesses. However, it is vital to clarify how the microbiome, through the release of microbial metabolites, impacts lung health and oncogenesis. Methods: In order to discover the powerful correlations between microbial metabolites and disease, we collected, under electronic bronchoscopy examinations, samples of paired bronchoalveolar lavage fluids (BALFs) from tumor-burden lung segments and ipsilateral non-tumor sites from 28 lung cancer participants, further performing metagenomic sequencing, short-chain fatty acid (SCFA) metabolomics, and multiomics analysis to uncover the potential correlations of the microbiome and SCFAs in lung cancer. Results: In comparison to BALFs from normal lung segments of the same participant, those from lung cancer burden lung segments had slightly decreased microbial diversity in the lower respiratory tract. With 18 differentially prevalent microbial species, including the well-known carcinogens Campylobacter jejuni and Nesseria polysaccharea, the relative species abundance in the lower respiratory tract microbiome did not significantly differ between the two groups. Additionally, a collection of commonly recognized probiotic metabolites called short-chain fatty acids showed little significance in either group independently but revealed a strong predictive value when using an integrated model by machine learning. Multiomics also discovered particular species related to SCFAs, showing a positive correlation with Brachyspira hydrosenteriae and a negative one with Pseudomonas at the genus level, despite limited detection in lower airways. Of note, these distinct microbiota and metabolites corresponded with clinical traits that still required confirmation. Conclusions: Further analysis of metagenome functional capacity revealed that genes encoding environmental information processing and metabolism pathways were enriched in the lower respiratory tract metagenomes of lung cancer patients, further supporting the oncogenesis function of various microbial species by different metabolites. These findings point to a potent relationship between particular components of the integrated microbiota-metabolites network and lung cancer, with implications for screening and diagnosis in clinical settings.

AIM2 fosters lung adenocarcinoma immune escape by modulating PD-L1 expression in tumor-associated macrophages via JAK/STAT3.

This work was devised to discuss the effect of AIM2 on the immunosuppression of LUAD tumors, as well as its molecular mechanism. An allograft mouse model was built. Mouse macrophages were isolated and collected. The infiltration level of Mø and expression of M1 Mø, M2 Mø markers, and PD-L1 were assayed by IHC and flow cytometry. Expression levels of M1 Mø and M2 Mø marker genes and PD-L1 were detected by qPCR. The expression of proteins linked with JAK/STAT3 was tested by western blot. CD8+T cells and NK cells were activated in vitro and co-cultured with mouse macrophages, and their cytotoxicity was detected by LDH method. The proportion of CD206+PD-L1+ cells and the activation and proliferation of CD8+T cells were assayed by flow cytometry. Multicolor immunofluorescence was utilized to assay the co-localization of proteins. AIM2 demonstrated a high expression in LUAD, exhibiting a conspicuous positive correlation with the expression of the M2 Mø markers as well as PD-L1. Expression of M1 markers was upregulated after knockdown of AIM2, while M2 markers expression and PD-L1 were downregulated, and the colocalization of proteins linked with PD-L1 and M2 Mø was decreased. The infiltration and cytotoxicity of CD8+T cells and NK cells increased after silencing AIM2. After the knockdown of AIM2, which was enriched in the JAK/STAT3 pathway, the phosphorylation levels of JAK1, JAK2, and STAT3 were reduced, the immune infiltration level of CD8+T cells increased, and the co-localization level of PD-L1 and PD-1 dropped. The activity and proliferation level of CD8+T cells were increased with the reduced PD-1 expression. AIM2 fosters M2 Mø polarization and PD-L1 expression via the JAK/STAT3 pathway. Moreover, AIM2 promotes the immune escape of LUAD via the PD-1/PD-L1 axis. Our work may blaze a trail for the clinical treatment of LUAD.

Accelerating the solar-thermal energy storage via inner-light supplying with optical waveguide.

Solar-thermal storage with phase-change material (PCM) plays an important role in solar energy utilization. However, most PCMs own low thermal conductivity which restricts the thermal charging rate in bulk samples and leads to low solar-thermal conversion efficiency. Here, we propose to regulate the solar-thermal conversion interface in spatial dimension by transmitting the sunlight into the paraffin-graphene composite with side-glowing optical waveguide fiber. This inner-light-supply mode avoids the overheating surface of the PCM, accelerates the charging rate by 123% than that of the traditional surface irradiation mode and increases the solar thermal efficiency to ~94.85%. Additionally, the large-scale device with inner-light-supply mode works efficiently outdoors, indicating the potential of this heat localization strategy in practical application.

The impact of hospital-family integrated continuation nursing based on information technology on patients unhealthy mood, family function and sexual function after cervical cancer surgery.

The objective of this study was to explore the impact on hospital-family integrated continuation care based on information technology on the negative emotions, family function, and sexual function of patients after cervical cancer surgery. The clinical case data onto 114 postoperative cervical cancer patients who were nursing in our hospital from July 2019 to July 2021 were selected and were divided into a control group and an observation group. The control group used routine nursing care, and on this basis, the observation group used information technology as the basis for hospital-family integrated continuation care, and we observed and compared the differences in the 2 groups of patients bad mood, family function, and sexual function. The score of anxiety (P = .017), depression (P = .009), fatigue rating (P = .012), and anger (P < .001) in the observation group after care were significantly lower than those in the control group. Problem solving, role, emotional response, emotional involvement, and family function total score in the observation group after care was significantly lower than those in the control group (P < .05). Sexual desire score, sexual arousal score, vaginal lubrication score, orgasm score, sexual satisfaction score, dyspareunia score, and Female Sexual Function Inventory total scores in the observation and control groups after care were significantly higher than those before care (P < .05). The sexual function scores in the observation group after care was significantly higher than those in the control group (P < .05). The hospital-family integrated continuation care based on information technology is more effective than conventional nursing care for patients after cervical cancer surgery.

Long-term auditory performance and psychosocial benefits of cochlear implantation in Mandarin-speaking older adults.

PURPOSE: Although previous studies have shown the efficacy of cochlear implants (CIs) in older adults, no study written in English has focused on Mandarin-speaking older recipients. Mandarin is a tonal language, it is hard to lip-read and tone recognition for CI users. This study aimed to evaluate the long-term post-CI outcomes in Mandarin-speaking older adults and the difference between them and younger recipients. MATERIALS AND METHODS: Forty-six post-lingually deafened adults were included. Speech perception tests (vowel, consonant, disyllable words, Mandarin monosyllable recognition test, and categories of audiology performance were evaluated) and psychosocial scale were evaluated. RESULTS: There were no significant differences between older and younger recipients in post-CI open-set speech perception. However, older recipients had significantly lower social and total scores in the subjective questionnaire than younger recipients. In both duration of deafness less than seven years and hearing years in life over 92.6 %, older recipients had no less capable speech perception than in younger. CONCLUSION: Mandarin-speaking older recipients can improve not only speech perception but also psychosocial benefits. Well hearing experience may confer an advantage to older recipients, despite their older implanted age. These results can help provide pre-CI consultation guidelines for older Mandarin-speaking recipients.

A universal hydrochloric acid-assistant powder-to-powder strategy for quick and mass preparation of lead-free perovskite microcrystals.

Lead-free halide perovskite materials possess low toxicity, broadband luminescence and robust stability compared with conventional lead-based perovskites, thus holding great promise for eyes-friendly white light LEDs. However, the traditionally used preparation methods with a long period and limited product yield have curtailed the commercialization of these materials. Here we introduce a universal hydrochloric acid-assistant powder-to-powder strategy which can accomplish the goals of thermal-, pressure-free, eco-friendliness, short time, low cost and high product yield, simultaneously. The obtained Cs2Na0.9Ag0.1In0.95Bi0.05Cl6 microcrystals exhibit bright self-trapped excitons emission with quantum yield of (98.3 ± 3.8)%, which could retain (90.5 ± 1.3)% and (96.8 ± 0.8)% after continuous heating or ultraviolet-irradiation for 1000 h, respectively. The phosphor converted-LED exhibited near-unity conversion efficiency from ultraviolet chip to self-trapped excitons emission at ~200 mA. Various ions doping (such as Cs2Na0.9Ag0.1InCl6:Ln3+) and other derived lead-free perovskite materials (such as Cs2ZrCl6 and Cs4MnBi2Cl12) with high luminous performance are all realized by our proposed strategy, which has shown excellent availability towards commercialization.

COVID-19 pandemic: impacts on air quality and economy before, during and after lockdown in China in 2020.

This paper comprehensively evaluates the dynamic effects on China's environment and economy during the COVID-19 pandemic. Results show that the COVID-19 lockdown resulted in a temporary improvement in air quality. Furthermore, nitrogen dioxide (NO2) levels in the atmosphere in China were 36% lower than in the week after last year's Lunar New Year holiday, but this also led to an economic downturn. Moreover, the aerosol optical depth (AOD) decreased significantly. During the back-to-work period, the economy recovered and there was an increase in energy consumption, and CO2, NO2 emissions sharply increased to pre-lockdown levels. In the post-lockdown period, the AOD was lower than that of the same period last year. This study can provide reference for environmental policy making, as it demonstrates to what extent the control of pollution sources can improve air quality. Precise emission reduction and regional joint prevention and control are important and effective means for the prevention and control of O3 pollution. The health and economic benefits of COVID-19 pandemic control measures are incalculable. And this can provide an effective scientific basis and theoretical support for the prevention and control of air pollution.

Combining a Density Gradient of Biomacromolecular Nanoparticles with Biological Effectors in an Electrospun Fiber-Based Nerve Guidance Conduit to Promote Peripheral Nerve Repair.

Peripheral nerve injury is a serious medical problem with limited surgical and clinical treatment options. It is of great significance to integrate multiple guidance cues in one platform of nerve guidance conduits (NGCs) to promote axonal elongation and functional recovery. Here, a multi-functional NGC is constructed to promote nerve regeneration by combining ordered topological structure, density gradient of biomacromolecular nanoparticles, and controlled delivery of biological effectors to provide the topographical, haptotactic, and biological cues, respectively. On the surface of aligned polycaprolactone nanofibers, a density gradient of bioactive nanoparticles capable of delivering recombinant human acidic fibroblast growth factor is deposited. On the graded scaffold, the proliferation of Schwann cells is promoted, and the directional extension of neurites from both PC12 cells and dorsal root ganglions is improved in the direction of increasing particle density. After being implanted in vivo for 6 and 12 weeks to repair a 10-mm rat sciatic nerve defect, the NGC promotes axonal elongation and remyelination, achieving the regeneration of the nerve not only in anatomical structure but also in functional recovery. Taken together, the NGC provides a favorable microenvironment for peripheral nerve regeneration and holds great promise for realizing nerve repair with an efficacy close to autograft.

The debatable role of immune checkpoint blockade therapy in lung adenocarcinoma-oriented liver metastatic malignant lesions.

BACKGROUND: The use of anti-PD-1 or PD-L1 inhibitors in combination with other anti-cancer agents was a priority for treating advanced non-small cell lung cancer (NSCLC) patients with considerable PD-L1 expression. However, studies seldom show the progression of liver metastases after using immune checkpoint inhibitors (ICIs). METHODS: Data were obtained from the Department of Pulmonary and Critical Care of Medicine, the First Affiliated Hospital of the Air Force Military Medical University. In the present study, we analyzed five non-small cell lung cancer (NSCLC) patients who had liver metastases after they were treated with pembrolizumab between 2019 and 2021. All of them had both stable primary lesions and liver progression with pembrolizumab intervention. Blood laboratory tests and imaging examinations were performed regularly during the treatment to assess the tumor responses of patients. RESULTS: All patients displayed reduction or stability in the initial lesions as a result, but they also experienced the emergence of metastatic liver locations, which were regularly detected throughout immunotherapy. Additionally, the appearance of liver metastasis weakened their liver function gradually with the escalation of carcinoembryonic antigen, regarded as a predictor for evaluating the progression of tumors. These individuals were highly distinctive with hyper-progressive diseases associated with immunotherapy. We drew individualized intervention schemes for metastatic lesions in each patient and found that their life expectancy shared no significance given the restricting subjected population. CONCLUSIONS: Our study indicated a clinical phenomenon after using immune checkpoint inhibitors and presented a necessity for implementing large scales clinical studies to manage NSCLC-oriented liver metastasis.

Effect of Crop Rotation on Fusarium Mycotoxins and Fusarium Species in Cereals in Sichuan Province (China).

The present study was performed to evaluate the effect of crop rotation on Fusarium mycotoxins and species in cereals in Sichuan Province. A total of 311 cereal samples were randomly collected and analyzed from 2018 to 2019 in Sichuan Province. The results of mycotoxin analysis showed that the major trichothecene mycotoxins in Sichuan Province were nivalenol (NIV) and deoxynivalenol (DON), and the mean concentration of total trichothecenes (including NIV, fusarenone X [4ANIV], DON, 3-acetyldeoxynivalenol [3ADON], and 15-acetyldeoxynivalenol [15ADON]) in wheat was significantly higher than that in maize and rice. The concentration of total trichothecenes in the succeeding crops was significantly higher than that in the previous crops. In addition, wheat grown after maize had reduced incidence and concentration of trichothecene mycotoxins compared with that grown after rice, and ratooning rice grown after rice had increased incidence and concentration of trichothecene mycotoxins. Our data indicated that Fusarium asiaticum with the NIV chemotype was predominant in wheat and rice samples, while the number of the NIV chemotypes of F. asiaticum and Fusarium meridionale and the 15ADON chemotype of Fusarium graminearum in maize were almost the same. Although the composition of Fusarium species was affected by crop rotations, there were no differences when comparing the same crop rotation except for the maize-wheat rotation. Moreover, the same species and chemotype of Fusarium strains originated from different crops in various rotations, but there were no significant differences in pathogenicity in wheat and rice. These results contribute to the knowledge of the effect of crop rotation on Fusarium mycotoxins and species affecting cereals in Sichuan Province, which may lead to improved strategies for control of Fusarium mycotoxins and fungal disease in China.

Microtubes with gradient decellularized porcine sciatic nerve matrix from microfluidics for sciatic nerve regeneration.

Long-range peripheral nerve defect is a severe and worldwide disease. With the increasing development of tissue engineering, the excellent ability of nerve extracellular matrix (ECM) in peripheral nerve injury (PNI) has been widely studied and verified. Here, we present a novel microtube that contains gradient decellularized porcine sciatic nerve ECM hydrogel (pDScNM-gel) from microfluidics for sciatic nerve regeneration. The pDScNM is confirmed to enhance cell proliferation and migration, and improve the axon growth of primary dorsal root ganglions (DRGs) in a concentration-related manner. These behaviors were also achieved when cells were co-cultured in a gradient pDScNM microtube. The in vivo sciatic nerve regeneration and functional recovery were also demonstrated by assembling the gradient pDScNM microtubes with a medical silicon tube. These results indicated that the microtubes with gradient pDScNM could act as a promising alternative for repairing peripheral nerve defects and showed great potential in clinical use.

Influence of Different Pt Functionalization Modes on the Properties of CuO Gas-Sensing Materials.

The functionalization of noble metals is an effective approach to lowering the sensing temperature and improving the sensitivity of metal oxide semiconductor (MOS)-based gas sensors. However, there is a dearth of comparative analyses regarding the differences in sensitization mechanisms between the two functionalization modes of noble metal loading and doping. In this investigation, we synthesized Pt-doped CuO gas-sensing materials using a one-pot hydrothermal method. And for Pt-loaded CuO, Pt was deposited on the synthesized pristine CuO surface by using a dipping method. We found that both functionalization methods can considerably enhance the response and selectivity of CuO toward NO2 at low temperatures. However, we observed that CuO with Pt loading had superior sensing performance at 25 °C, while CuO with Pt doping showed more substantial response changes with an increase in the operating temperature. This is mainly due to the different dominant roles of electron sensitization and chemical sensitization resulting from the different forms of Pt present in different functionalization modes. For Pt doping, electron sensitization is stronger, and for Pt loading, chemical sensitization is stronger. The results of this study present innovative ideas for understanding the optimization of noble metal functionalization for the gas-sensing performance of metal oxide semiconductors.

Modulation of PC1/3 activity by a rare double-site homozygous mutation.

Objectives: Preprotein convertase 1/3 deficiency is a rare autosomal recessive disorder in which patients present with malabsorptive diarrhea and a series of symptoms of endocrine disorders such as polydipsia, reactive hypoglycemia, growth hormone deficiency, hypothyroidism, adrenal insufficiency, and early onset obesity. In its essence, pituitary hormone deficiency is caused by insufficient cleavage of pituitary prohormones. Here, we describe a female child with a rare double-site homozygous mutation in PCSK1 (Proprotein convertase subtilisin/kexin-type 1) gene, and thereby intend to investigate the relationship between these novel mutation sites and changes in protein synthesis and function. Methods: We tested this patient's blood and urine fecal indicators of infection, blood electrolytes, and relevant endocrine hormone levels in the laboratory. Next Generation Sequencing was applied to screen the patient's DNA. Western Blot was performed to evaluate the mutant protein's expression. The enzymatic activity was measured as the rate of cleavage of a synthetic fluorogenic substrate in a specific solution. Results: We found that this patient presented shortly after birth with uncorrectable diarrhea and symptoms of metabolic acidosis with hypothyroidism. Next Generation Sequencing revealed that a rare double-site homozygous missense mutation, c.763G > A (p.G255R) and c.758C > T (p.S253L), were detected in exon 7 of PCSK1 (Proprotein convertase subtilisin/kexin-type 1) gene on chromosome 5 of the patient. Western blotting revealed that there was no significant decrease in protein synthesis levels in the mutant phenotype compared to the wild type. Compared with WT type, the proteins expressed by the mutations showed a significant decrease in the enzyme activity towards the fluorescent substrates. However, neither the single site mutation p.S253L or p.G255R, nor the double-site mutation of both, all showed no significant differences from each other. Conclusions: These two missense mutations have not been reported before, and it is even rarer to find homozygous variation of two sites in one patient. This study identifies two novel mutations for the first time and further investigates the changes in protein synthesis and enzyme activity, providing a new pathway to continue to explore the pathogenesis of diseases associated with the function of PC1/3.

Structural and Functional Responses of the Heteromorphic Leaves of Different Tree Heights on Populus euphratica Oliv. to Different Soil Moisture Conditions.

Populus euphratica Oliv., a pioneer species of desert riparian forest, is characterized heterophylly. To understand the adaptation strategies of the heteromorphic leaves of P. euphratica to soil drought, we assessed the structural and functional characteristics of the heteromorphic leaves at different heights in suitable soil moisture conditions (groundwater depth 1.5 m) and drought conditions (groundwater depth 5 m), which include morphology, anatomical structure, photosynthetic capacity, water use efficiency, osmotic adjustment capacity, and endogenous hormones. These results indicate that leaf area, leaf thickness, fence tissue, palisade-to-sea ratio, main vein xylem area, vessel area, net photosynthetic rate, transpiration rate, and proline, MDA, IAA, GA3, and ZR contents showed a positive correlation with the tree height under the two soil moisture conditions, but leaf shape index, leaf water potential (LWP), and ABA content showed a decreasing trend. In addition, the main vein vascular bundle area, main vein xylem area, and contents of malondialdehyde, ABA, GA3, and IAA were significantly greater under soil drought conditions than normal soil water content. Under soil drought stress, the heteromorphic leaves of P. euphratica showed more investment in anatomical structure and greater water use efficiency, proline, and hormone contents, and synergistic changes to maintain high photosynthetic efficiency. This is an adaptation strategy to water stress caused by soil drought and tree height changes.