Search

Abstract The 2-oxoglutarate dehydrogenase complex (OGDHc) orchestrates a critical reaction regulating the TCA cycle. Although the structure of each OGDHc subunit has been solved, the architecture of the intact complex and inter-subunit interactions still remain unknown. Here we report the assembly of native, intact OGDHc from Sus scrofa heart tissue using cryo-electron microscopy (cryo-EM), cryo-electron tomography (cryo-ET), and subtomogram averaging (STA) to discern native structures of the whole complex and each subunit. Our cryo-EM analyses revealed the E2o cubic core structure comprising eight homotrimers at 3.3-Å resolution. More importantly, the numbers, positions and orientations of each OGDHc subunit were determined by cryo-ET and the STA structures of the core were resolved at 7.9-Å with the peripheral subunits reaching nanometer resolution. Although the distribution of the peripheral subunits E1o and E3 vary among complexes, they demonstrate a certain regularity within the position and orientation. Moreover, we analyzed and validated the interactions between each subunit, and determined the flexible binding mode for E1o, E2o and E3, resulting in a proposed model of Sus scrofa OGDHc. Together, our results reveal distinctive factors driving the architecture of the intact, native OGDHc.

Abstract Enzymatic breakdown of sphingomyelin by sphingomyelinase (SMase) is the main source of the membrane lipids, ceramides, which are involved in many cellular physiological processes. However, the full-length structure of human neutral SMase has not been resolved; therefore, its catalytic mechanism remains unknown. Here, we resolve the structure of human full-length neutral SMase, sphingomyelinase 1 (SMPD2), which reveals that C-terminal transmembrane helices contribute to dimeric architecture of hSMPD2 and that D111 − K116 loop domain is essential for substrate hydrolysis. Coupled with molecular docking, we clarify the binding pose of sphingomyelin, and site-directed mutagenesis further confirms key residues responsible for sphingomyelin binding. Hybrid quantum mechanics/molecular mechanics (QM/MM) molecular dynamic (MD) simulations are utilized to elaborate the catalysis of hSMPD2 with the reported in vitro substrates, sphingomyelin and lyso-platelet activating fator (lyso-PAF). Our study provides mechanistic details that enhance our knowledge of lipid metabolism and may lead to an improved understanding of ceramide in disease and in cancer treatment.

Diabetic neuropathy is the most common complication of diabetes and lacks effective treatments. Although sensory dysfunction during the early stages of diabetes has been extensively studied in various animal models, the functional and morphological alterations in sensory and motor systems during late stages of diabetes remain largely unexplored. In the current work, we examined the influence of diabetes on sensory and motor function as well as morphological changes in late stages of diabetes. The obese diabetic Leprdb/db mice (db/db) were used for behavioral assessments and subsequent morphological examinations. The db/db mice exhibited severe sensory and motor behavioral defects at the age of 32 weeks, including significantly higher mechanical withdrawal threshold and thermal latency of hindpaws compared with age-matched nondiabetic control animals. The impaired response to noxious stimuli was mainly associated with the remarkable loss of epidermal sensory fibers, particularly CGRP-positive nociceptive fibers. Unexpectedly, the area of CGRP-positive terminals in the spinal dorsal horn was dramatically increased in diabetic mice, which was presumably associated with microglial activation. In addition, the db/db mice showed significantly more foot slips and took longer time during the beam-walking examination compared with controls. Meanwhile, the running duration in the rotarod test was markedly reduced in db/db mice. The observed sensorimotor deficits and motor dysfunction were largely attributed to abnormal sensory feedback and muscle atrophy as well as attenuated neuromuscular transmission in aged diabetic mice. Morphological analysis of neuromuscular junctions (NMJs) demonstrated partial denervation of NMJs and obvious fragmentation of acetylcholine receptors (AChRs). Intrafusal muscle atrophy and abnormal muscle spindle innervation were also detected in db/db mice. Additionally, the number of VGLUT1-positive excitatory boutons on motor neurons was profoundly increased in aged diabetic mice as compared to controls. Nevertheless, inhibitory synaptic inputs onto motor neurons were similar between the two groups. This excitation-inhibition imbalance in synaptic transmission might be implicated in the disturbed locomotion. Collectively, these results suggest that severe sensory and motor deficits are present in late stages of diabetes. This study contributes to our understanding of mechanisms underlying neurological dysfunction during diabetes progression and helps to identify novel therapeutic interventions for patients with diabetic neuropathy.

To ensure the water quality of rivers, it is crucial to scientifically evaluate their water quality status. This study takes a river in Jiangsu, China, as an example to establish six targeted main indicators for river water quality evaluation and uses a projection pursuit model optimized by the genetic algorithm to determine weights. Applying the improved fuzzy evaluation model to the final evaluation of water quality, the results indicate that this article adopts a weight calculation model that reduces dimensionality without losing data features, and the comprehensive evaluation model is also more complete, resulting in more accurate evaluation results. According to model analysis, the summer water quality is good and peaks from June to July. This article proposes corresponding measures and suggestions in response to the reasons behind this seasonal change. The evaluation model used in this article is superior to other models in terms of accuracy and portability, making it an excellent choice for river water quality evaluation. It can provide valuable technical guidance for similar river water quality evaluations. HIGHLIGHTS In the evaluation of river water quality, the high-dimensional data dimensionality reduction operation optimized by the genetic algorithm projection pursuit (GA-PP) is not easy to lose the original features of the data and is quite suitable for calculating weights.; The improved fuzzy evaluation model is also superior to the traditional fuzzy comprehensive model and can more comprehensively evaluate water quality data.;

Abstract Dysregulation of pathogen-recognition pathways of the innate immune system is associated with multiple autoimmune disorders. Due to the intricacies of the molecular network involved, the identification of pathway- and disease-specific therapeutics has been challenging. Using a phenotypic assay monitoring the degradation of the immune adapter TASL, we identify feeblin, a chemical entity which inhibits the nucleic acid-sensing TLR7/8 pathway activating IRF5 by disrupting the SLC15A4-TASL adapter module. A high-resolution cryo-EM structure of feeblin with SLC15A4 reveals that the inhibitor binds a lysosomal outward-open conformation incompatible with TASL binding on the cytoplasmic side, leading to degradation of TASL. This mechanism of action exploits a conformational switch and converts a target-binding event into proteostatic regulation of the effector protein TASL, interrupting the TLR7/8-IRF5 signaling pathway and preventing downstream proinflammatory responses. Considering that all components involved have been genetically associated with systemic lupus erythematosus and that feeblin blocks responses in disease-relevant human immune cells from patients, the study represents a proof-of-concept for the development of therapeutics against this disease.

Abstract Toll-like receptors (TLRs) are a class of proteins that play critical roles in recognizing pathogens and initiating innate immune responses. TASL, a recently identified innate immune adaptor protein for endolysosomal TLR7/8/9 signaling, is recruited by the lysosomal proton-coupled amino-acid transporter SLC15A4, and then activates IRF5, which in turn triggers the transcription of type I interferons and cytokines. Here, we report three cryo-electron microscopy (cryo-EM) structures of human SLC15A4 in the apo monomeric and dimeric state and as a TASL-bound complex. The apo forms are in an outward-facing conformation, with the dimeric form showing an extensive interface involving four cholesterol molecules. The structure of the TASL-bound complex reveals an unprecedented interaction mode with solute carriers. During the recruitment of TASL, SLC15A4 undergoes a conformational change from an outward-facing, lysosomal lumen-exposed state to an inward-facing state to form a binding pocket, allowing the N-terminal helix of TASL to be inserted into. Our findings provide insights into the molecular basis of regulatory switch involving a human solute carrier and offers an important framework for structure-guided drug discovery targeting SLC15A4-TASL-related human autoimmune diseases.

In biomedicine, the critical task is to decode Drug–Drug Interactions (DDIs) from complex biomedical texts. The scientific community employs Knowledge Graph Embedding (KGE) methods, enhanced with advanced neural network technologies, including capsule networks. However, existing methodologies primarily focus on the structural details of individual entities or relations within Biomedical Knowledge Graphs (BioKGs), overlooking the overall structural context of BioKGs, molecular structures, positional features of drug pairs, and their critical Relational Mapping Properties. To tackle the challenges identified, this study presents HSTrHouse an innovative hierarchical self-attention BioKGs embedding framework. This architecture integrates self-attention mechanisms with advanced neural network technologies, including Convolutional Neural Network (CNN) and Graph Neural Network (GNN), for enhanced computational modeling in biomedical contexts. The model bifurcates the BioKGs into entity and relation layers for structural analysis. It employs self-attention across these layers, utilizing PubMedBERT and CNN for position feature extraction, and a GNN for drug pair molecular structure analysis. Then, we connect the position and molecular structure features to integrate them into the self-attention calculation of entity and relation. After that, the output of the self-attention layer is combined with the connected vectors of the position feature and molecular structure feature to obtain the final representation vector, and finally, to model the Relational Mapping Properties (RMPs), the representation vector is embedded into the complex vector space using Householder projections to obtain the BioKGs model. The paper validates HSTrHouse’s efficacy by comparing it with advanced models on three standard BioKGs for DDIs research.

Zeaxanthin dipalmitate (ZD) is a chemical extracted from wolfberry that protects degenerated photoreceptors in mouse retina. However, the pure ZD is expensive and hard to produce. In this study, we developed a method to enrich ZD from wolfberry on a production line and examined whether it may also protect the degenerated mouse retina. The ZD-enriched wolfberry extract (ZDE) was extracted from wolfberry by organic solvent method, and the concentration of ZD was identified by HPLC. The adult C57BL/6 mice were treated with ZDE or solvent by daily gavage for 2 weeks, at the end of the first week the animals were intraperitoneally injected with N-methyl-N-nitrosourea to induce photoreceptor degeneration. Then optomotor, electroretinogram, and immunostaining were used to test the visual behavior, retinal light responses, and structure. The final ZDE product contained ~30mg/g ZD, which was over 9 times higher than that from the dry fruit of wolfberry. Feeding degenerated mice with ZDE significantly improved the survival of photoreceptors, enhanced the retinal light responses and the visual acuity. Therefore, our ZDE product successfully alleviated retinal morphological and functional degeneration in mouse retina, which may provide a basis for further animal studies for possible applying ZDE as a supplement to treat degenerated photoreceptor in the clinic.

Objectives: We aimed to explore the relationship among intolerance of uncertainty (IU), rumination, anxiety, and smartphone dependence (SPD) in preservice teachers during the COVID-19 pandemic. Methods: Two cross-sectional studies were conducted with Chinese preservice teachers, using questionnaires on IU, rumination, anxiety, and SPD. Data were analyzed using AMOS 24.0 and SPSS 25.0, and the mediating mechanism was tested using the macro program Model 6. Study 1 recruited participants who were forcibly sequestered in a university due to an anti-epidemic policy during the COVID-19 crisis. Study 2 was surveyed online from different universities to replicate and enhance the reliability of Study 1 finding. Results: Study 1 (N = 553, Mage = 20.8 ± 2.3, 30.0% female) and Study 2 (N = 1610, Mage = 21.1 ± 2.1, 51.4% female) both found that IU affected SPD through the independent mediators of rumination and anxiety, as well as the chain mediation of rumination→ anxiety. In Study 1, the indirect effect of IU on SPD was significant through rumination (β = 0.16, 95% CI [0.03, 0.06]), anxiety (β = 0.11, 95% CI [0.03, 0.06]), and the chain mediation (β = 0.02, 95% CI [0.01, 0.04]); in Study 2, the indirect effect of IU on SPD was significant through rumination (β = 0.08, 95% CI [0.05, 0.11]), anxiety (β = 0.10, 95% CI [0.08, 0.13]), and the chain mediation (β = 0.02, 95% CI [0.02, 0.03]). Conclusion: Two cross-sectional studies found that preservice teachers’ SPD is indirectly connected to IU, mediated by rumination and anxiety, and weakly mediated by the chain mediation of rumination and anxiety. Our findings may help educators understand the impact of anti-epidemic policies on preservice teachers and possible inclusive later interventions.

IntroductionInappropriate residue and nutrient management leads to soil degradation and the decline of soil quality and water storage capacity.MethodsAn ongoing field experiment has been conducted since 2011 to investigate the effects of straw mulching (SM), and straw mulching combined with organic fertilizer (SM+O), on winter wheat yield, including a control treatment (CK, no straw). We studied the effects of these treatments on soil microbial biomass nitrogen and carbon, soil enzyme activity in 2019, photosynthetic parameters, evapotranspiration (ET), water use efficiency (WUE), and yields over five consecutive years (2015-2019). We also analyzed the soil organic carbon, soil structure, field capacity, and saturated hydraulic conductivity in 2015 and 2019. ResultsResults indicate that compared with CK, SM and SM+O treatments increased the proportion of >0.25mm aggregates, soil organic carbon, field capacity, and saturated hydraulic conductivity, but decreased the soil bulk density. In addition, the SM and SM+O treatments also increased soil microbial biomass nitrogen and carbon, the activity of soil enzymes, and decreased the carbon-nitrogen ratio of microbial biomass. Therefore, SM and SM+O treatments both increased the leaf water use efficiency (LWUE) and photosynthetic rate (Pn), and improved the yields and water use efficiency (WUE) of winter wheat. The combination SM (4.5 t/ha)+O (0.75 t/ha) was more effective than SM alone, and both treatments were superior to the control.ConclusionBased on the results of this study, SM+O is recommended as the most effective cultivation practice.

Background: Following China’s strategy of developing applied and compound social talents, vocational undergraduates are surging rapidly, and it is essential to understand the causes of their depression to effectively prevent and intervene in schools. Objective: We aimed to investigate the relationship between negative life events (NLEs) and depression among vocational undergraduates in China, along with the mediating role of loneliness and the moderating role of socioeconomic status (SES). Methods: A convenience sample survey was conducted at a vocational education university (N = 1487), and analyzed using partial least squares structural equation modeling. Results: Findings showed that NLEs directly predicted depression (β = 0.399, 95% CI [0.339, 0.452], p < 0.001) among vocational undergraduates. Furthermore, this relationship was partially mediated by loneliness (β = 0.182, 95% CI [0.145, 221], p < 0.001); SES moderated the link between NLEs and depression (β = 0.051, 95% CI [0.004, 092], p < 0.05), but not between NLEs and loneliness (p > 0.05). Conclusions: The current study highlights the impact of NLEs on depression among vocational undergraduates, indicating the importance of addressing NLEs and consequent feelings of loneliness to promote mental health. In addition, the moderating role of SES underscores the necessity of targeted interventions to mitigate the impact of NLEs on depression. The present study contributes to our understanding of the unique characteristics of depression in vocational undergraduates and has practical implications for psychological support services. Moreover, it probably has broader implications for addressing mental health challenges in global education settings for vocational undergraduates.

The prevalence of depression among adolescents is increasing, which can hinder their healthy development and is intricately linked to the intolerance of uncertainty (IU). IU involves both prospective anxiety and inhibitory anxiety. However, the precise relationship between depressive symptoms and these two components of IU remains unclear, particularly when considering the specific context of rural adolescents in China. A total of 1488 adolescents (male, 848; Meanage = 20, SDage = 1.51, age range from 16 to 24) in China were recruited and divided into urban adolescents (N = 439) and rural adolescents (N = 1049) groups. The Patient Health Questionnaire-9 and Intolerance of Uncertainty Scale-12 were utilized to measure depression and IU. The symptom network approach and the flow network approach were employed. The prevalence of depression was significantly higher (χ2 = 4.09, p = 0.04) among rural adolescents (N = 419, 40.1%) than urban adolescents (N = 152, 34.8%). The node strength of “motor” demonstrated some discrepancy between rural and urban adolescents, while there was no notable disparity in the global strength and structure of the network between the two groups. However, rural adolescents exhibited a significantly higher global strength in the flow network (including depression and IU) than their urban counterparts. In the flow networks of rural adolescents, “guilt” was directly associated with prospective and inhibitory anxiety. These findings highlight the urgent need for interventions that enhance the ability of rural adolescents to cope with uncertainty and prevent their depressive symptoms more effectively.

Abstract Polyamines are important polycations that play critical roles in mammalian cells. ATP13A2 belongs to the orphan P5B adenosine triphosphatases (ATPase) family and has been established as a lysosomal polyamine exporter to maintain the normal function of lysosomes and mitochondria. Previous studies have reported that several human neurodegenerative disorders are related to mutations in the ATP13A2 gene. However, the transport mechanism of ATP13A2 in the lysosome remains unclear. Here, we report the cryo-electron microscopy (cryo-EM) structures of three distinct intermediates of the human ATP13A2, revealing key insights into the spermine (SPM) transport cycle in the lysosome. The transmembrane domain serves as a substrate binding site and the C-terminal domain is essential for protein stability and may play a regulatory role. These findings advance our understanding of the polyamine transport mechanism, the lipid-associated regulation, and the disease-associated mutants of ATP13A2.

IntroductionWater scarcity and seasonal drought are major constraints on agricultural development globally. Super absorbent polymer (SAP) is a good amendment that can improve soil structure, increase soil water retention, and promote crop growth even with less soil moisture. We hypothesize that long term application of SAP has a better effect on soil organic carbon, soil enzyme activity, photosynthetic characteristics, yield, and water and nitrogen use than short term application. MethodsA long term field experiment with different application rates (0 (CK), 15 (L), 30 (M), 45 (H) kg ha-1) of SAP was conducted at the Yuzhou water conservation agriculture base of the Henan Academy of Agricultural Sciences from 2011 to 2019.Results and DiscussionThe results indicate that applying SAP increases > 0.25 mm aggregates and decreased

Abstract ABCB6 plays a crucial role in energy-dependent porphyrin transport, drug resistance, toxic metal resistance, porphyrin biosynthesis, protection against stress, and encoding a blood group system Langereis antigen. However, the mechanism underlying porphyrin transport is still unclear. Here, we determined the cryo-electron microscopy (cryo-EM) structures of nanodisc-reconstituted human ABCB6 trapped in an apo-state and an ATP-bound state at resolutions of 3.6 and 3.5 Å, respectively. Our structures reveal a unique loop in the transmembrane domain (TMD) of ABCB6, which divides the TMD into two cavities. It restrains the access of substrates in the inward-facing state and is removed by ATP-driven conformational change. No ligand cavities were observed in the nucleotide-bound state, indicating a state following substrate release but prior to ATP hydrolysis. Structural analyses and functional characterizations suggest an “ATP-switch” model and further reveal the conformational changes of the substrate-binding pockets triggered by the ATP-driven regulation.

Abstract Pannexin1 (PANX1) is a large-pore ATP efflux channel with a broad distribution, which allows the exchange of molecules and ions smaller than 1 kDa between the cytoplasm and extracellular space. In this study, we show that in human macrophages PANX1 expression is upregulated by diverse stimuli that promote pyroptosis, which is reminiscent of the previously reported lipopolysaccharide-induced upregulation of PANX1 during inflammasome activation. To further elucidate the function of PANX1, we propose the full-length human Pannexin1 (hPANX1) model through cryo-electron microscopy (cryo-EM) and molecular dynamics (MD) simulation studies, establishing hPANX1 as a homo-heptamer and revealing that both the N-termini and C-termini protrude deeply into the channel pore funnel. MD simulations also elucidate key energetic features governing the channel that lay a foundation to understand the channel gating mechanism. Structural analyses, functional characterizations, and computational studies support the current hPANX1-MD model, suggesting the potential role of hPANX1 in pyroptosis during immune responses.

ObjectiveThe aim of the study was to explore the relationship among gratitude, meaning in life (MIL), career calling, and career goal self-efficacy (CGSE) of the pre-service teachers in the Free Teacher Education program in China and the internal mechanism of action.MethodsIn this study, gratitude, MIL, career calling, and CGSE questionnaires were used to investigate 801 pre-service teachers. IBM SPSS 25.0 and AMOS 24.0 were used for data processing, and SPSS macro program Model 6 was used for the mediating mechanism.Results(1) Gratitude was positively correlated with MIL and career calling. MIL was positively correlated with career calling. Gratitude, MIL, and career calling were significantly and positively associated with CGSE. (2) Gratitude influences pre-service teachers’ CGSE mainly through the independent intermediary of MIL and career calling, and the chain intermediary of MIL→career calling, three indirect effects.ConclusionGratitude indirectly predicts CGSE of pre-service teachers not only through the independent intermediary of MIL and career calling but also through the chain intermediary of MIL and career calling.

Zhang et al. present the cryo-electron microscopy structures of the two neuronal cation-chloride cotransporters human NKCC1 and mouse KCC2, identifying their essential residues for ion transport. This study proposes mechanisms by which phosphorylation regulates the activity of these cation-chloride cotransporters.

Abstract Background MicroRNAs (miRNAs) have been reported to serve pivotal roles in tumorigenesis. This study sough to assess the expression and clinical significance of microRNA-1298 (miR-1298) in patients with non-small cell lung cancer (NSCLC), and explore the functional role of miR-1298 in tumorigenesis. Methods One hundred and twenty-one NSCLC patients were recruited in this study. The expression of miR-1298 was estimated using quantitative real-time PCR. Kaplan-Meier survival curves and Cox regression analysis were used to evaluate the prognostic value of miR-1298. Gain- and loss-of-function experiments were preformed to explore the biological function of miR-1298 in NSCLC cells. Results Expression levels of miR-1298 were downregulated in NSCLC tissues and cells compared with the corresponding normal controls. The decreased expression of miR-1298 was associated with patients’ lymph node metastasis and TNM stage. The low expression of miR-1298 predicted poor overall survival and served as an independent prognostic indicator in NSCLC patients. According to the cell experiments, NSCLC cell proliferation, migration and invasion were inhibited by the overexpression of miR-1298. Conclusion All the data indicated that the downregulation of miR-1298 predicts poor prognosis of NSCLC, and the overexpression of miR-1298 in NSCLC cells leads to inhibited tumorigenesis. The aberrant miR-1298 may serve as a novel biomarker and therapeutic target in NSCLC.

One of the major challenges in treating Alzheimer's disease (AD) is its early diagnosis. Increasing data from clinical and animal research indicate that the retina may facilitate an early diagnosis of AD. However, a previous study on the 5xFAD (a fast AD model), showing retinal changes before those in the brain, has been questioned because of the involvement of the retinal degeneration allele Pde6brd1. Here, we tested in parallel, at 4 and 6 months of age, both the retinal and the brain structure and function in a 5xFAD mouse line that carries no mutation of rd1. In the three tested regions of the 5xFAD brain (hippocampus, visual cortex, and olfactory bulb), the Aβ plaques were more numerous than in wild-type (WT) littermates already at 4 months, but deterioration in the cognitive behavioral test and long-term potentiation (LTP) lagged behind, showing significant deterioration only at 6 months. Similarly in the retina, structural changes preceded functional decay. At 4 months, the retina was generally normal except for a thicker outer nuclear layer in the middle region than WT. At 6 months, the visual behavior (as seen by an optomotor test) was clearly impaired. While the full-field and pattern electroretinogram (ERG) responses were relatively normal, the light responses of the retinal ganglion cells (measured with multielectrode-array recording) were decreased. Structurally, the retina became abnormally thick with few more Aβ plaques and activated glia cells. In conclusion, the timeline of the degenerative processes in the retina and the brain is similar, supporting the use of non-invasive methods to test the retinal structure and function to reflect changes in the brain for early AD diagnosis.

Abstract TRPML1 channel is a non-selective group-2 transient receptor potential (TRP) channel with Ca2+ permeability. Located mainly in late endosome and lysosome of all mammalian cell types, TRPML1 is indispensable in the processes of endocytosis, membrane trafficking, and lysosome biogenesis. Mutations of TRPML1 cause a severe lysosomal storage disorder called mucolipidosis type IV (MLIV). In the present study, we determined the cryo-electron microscopy (cryo-EM) structures of Mus musculus TRPML1 (mTRPML1) in lipid nanodiscs and Amphipols. Two distinct states of mTRPML1 in Amphipols are added to the closed state, on which could represent two different confirmations upon activation and regulation. The polycystin-mucolipin domain (PMD) may sense the luminal/extracellular stimuli and undergo a “move upward” motion during endocytosis, thus triggering the overall conformational change in TRPML1. Based on the structural comparisons, we propose TRPML1 is regulated by pH, Ca2+, and phosphoinositides in a combined manner so as to accommodate the dynamic endocytosis process.

A variable-exponent taper equation was developed for Chinese fir (Cunninghamia lanceolate (Lamb.) Hook.) trees grown in southern China. Thirty taper equations from different groups of models (single, segmented, or variable-exponent taper equation) were compared to find the excellent basic model with S-plus software. The lowest Akaike information criteria (AIC), Bayesian information criteria (BIC), and -2loglikelihood (-2LL) was chosen to determine the best combination of random parameters. Single taper models were found having the lowest precision, and the variable-exponent taper equations had higher precision than the segmented taper equations. Four variable-exponent taper models that developed by Zeng and Liao, Bi, Kozak, Sharma, and Zhang respectively, were selected as basic model and had no difference in fit statistics between them. Compared with the model without seldom parameter, the nonlinear mixed-effects (NLME) model improves the fitting performance. The plot-level NLME model was found not to remove the residual autocorrelation. The tree-level and two-level NLME model had better simulation accuracy than the plot-level NLME model, and there were no significant differences between the tree-level and two-level NLME model. Variable-exponent taper model developed by Kozak showed the best performance while considering two-level or tree-level NLME model, and produced better predictions for medium stems compared to lower and upper stems.

Chinese fir (Cunninghamia lanceolata) is the most important commercial tree species in southern China. The objective of this study was to develop a variable taper equation for Chinese fir, and to quantify the effects of stand planting density on stem taper in Chinese fir. Five equations were fitted or evaluated using the diameter-height data from 293 Chinese fir trees sampled from stands with four different densities in Fenyi County, Jiangxi Province, in southern China. A total of 183 trees were randomly selected for the model development, with the remaining 110 trees used for model evaluation. The results show that the Kozak’s, Sharma/Oderwald, Sharma/Zhang and modified Brink’s equations are superior to the Pain/Boyer equation in terms of the fitting and validation statistics, and the modified Brink’s and Sharma/Zhang equations should be recommended for use as taper equations for Chinese fir because of their high accuracy and variable exponent. The relationships between some parameters of the three selected equations and stand planting densities can be built by adopting some simple mathematical functions to examine the effects of stand planting density on tree taper. The modelling and prediction precision of the three taper equations were compared with or without incorporation of the stand density variable. The predictive accuracy of the model was improved by including the stand density variable and the mean absolute bias of the modified Brink’s and Sharma/Zhang equations with a stand density variable were all below 1.0 cm in the study area. The modelling results showed that the trees have larger butt diameters and more taper when stand density was lower than at higher stand density.

The article presents a study deepens understanding of CLC-7/Ostm1 transporter and provides insights into the molecular basis of the disease-related mutations. It mentions that CLC family proteins translocate chloride ions across cell membranes to maintain the membrane potential, regulate the transepithelial Cl− transport, and control the intravesicular pH among different organelles.