Multi-feature, Chinese-Western medicine-integrated prediction model for diabetic peripheral neuropathy based on machine learning and SHAP.

BACKGROUND: Clinical studies have shown that diabetic peripheral neuropathy (DPN) has been on the rise, with most patients presenting with severe and progressive symptoms. Currently, most of the available prediction models for DPN are derived from general clinical information and laboratory indicators. Several Traditional Chinese medicine (TCM) indicators have been utilised to construct prediction models. In this study, we established a novel machine learning-based multi-featured Chinese-Western medicine-integrated prediction model for DPN using clinical features of TCM. MATERIALS AND METHODS: The clinical data of 1581 patients with Type 2 diabetes mellitus (T2DM) treated at the Department of Endocrinology of the First Affiliated Hospital of Anhui University of Chinese Medicine were collected. The data (including general information, laboratory parameters and TCM features) of 1142 patients with T2DM were selected after data cleaning. After baseline description analysis of the variables, the data were divided into training and validation sets. Four prediction models were established and their performance was evaluated using validation sets. Meanwhile, the accuracy, precision, recall, F1 score and area under the curve (AUC) of ROC were calculated using ten-fold cross-validation to further assess the performance of the models. An explanatory analysis of the results of the DPN prediction model was carried out using the SHAP framework based on machine learning-based prediction models. RESULTS: Of the 1142 patients with T2DM, 681 had a comorbidity of DPN, while 461 did not. There was a significant difference between the two groups in terms of age, cause of disease, systolic pressure, HbA1c, ALT, RBC, Cr, BUN, red blood cells in the urine, glucose in the urine, and protein in the urine (p < 0.05). T2DM patients with a comorbidity of DPN exhibited diverse TCM symptoms, including limb numbness, limb pain, hypodynamia, thirst with desire for drinks, dry mouth and throat, blurred vision, gloomy complexion, and unsmooth pulse, with statistically significant differences (p < 0.05). Our results showed that the proposed multi-featured Chinese-Western medicine-integrated prediction model was superior to conventional models without characteristic TCM indicators. The model showed the best performance (accuracy = 0.8109, precision = 0.8029, recall = 0.9060, F1 score = 0.8511, and AUC = 0.9002). SHAP analysis revealed that the dominant risk factors that caused DPN were TCM symptoms (limb numbness, thirst with desire for drinks, blurred vision), age, cause of disease, and glycosylated haemoglobin. These risk factors were exerted positive effects on the DPN prediction models. CONCLUSIONS: A multi-feature, Chinese-Western medicine-integrated prediction model for DPN was established and validated. The model improves early-stage identification of high-risk groups for DPN in the diagnosis and treatment of T2DM, while also providing informative support for the intelligent management of chronic conditions such as diabetes.

The effects of psychological distress after surgery in patients undergoing lumbar spinal fusion.

BACKGROUND: The aim of this study was to evaluate the psychological distress pre-operatively, at 3, 6, and 12 months in patients who underwent lumbar spine fusion surgery. METHODS: A total of 440 patients received instrumented lumbar spine fusion were enrolled. Psychological distress was evaluated using the Modified Somatic Perception Questionnaire (MSPQ) and the Modified Zung Depressive Index (ZDI). The results of lumbar fusion surgery were evaluated using the Oswestry Disability Index (ODI), the Japanese Orthopedic Association (JOA-29), and the visual analog scale (VAS). RESULTS: Psychological distress was reported among 23% of patients and 7, 5.5, and 4.0% of the patients preoperatively, at 3, 6, and 12 months after lumbar surgery, respectively. The mean MSPQ score decreased from 8.78 (before surgery) to 4.30, 3.52, and 3.43 at 3, 6 and 12 months in after surgery, respectively, in patients with psychological distress patients (p < 0.001). The mean ZDI score decreased from 17.78 to 12.48, 10.35, and 9.61 (p < 0.001). The mean ODI score decreased from 22.91 to 11.78, 10.13, and 9.96 (P < 0.001). The mean JOA score increased from 13.65 to 22.30, 23.43, and 23.61 (P < 0.001). The mean low back pain (LBP) VAS score decreased from 4.48 to 1.96, 1.52, and 1.51 (P < 0.001); moreover, the mean leg pain (LP) VAS score decreased from 5.30 to 1.30, 1.04, and 1.03 (P < 0.001). CONCLUSIONS: Patients with psychological distress may experience surgical intervention benefits equal to those of ordinary patients. Moreover, reduced pain and disability after surgical intervention may also alleviate psychological distress. Hence, we highly recommend that patients with psychological distress undergo surgical intervention as normal patients do, but appropriate screening measures and interventions are necessary.

Successive accumulation of biotic assemblages at a fine spatial scale along glacier-fed waters.

Glacier-fed waters create strong environmental filtering for biota, whereby different organisms may assume distinct distribution patterns. By using environmental DNA-based metabarcoding, we investigated the multi-group biodiversity distribution patterns of the Parlung No. 4 Glacier, on the Tibetan Plateau. Altogether, 642 taxa were identified from the meltwater stream and the downstream Ranwu Lake, including 125 cyanobacteria, 316 diatom, 183 invertebrate, and 18 vertebrate taxa. As the distance increased from the glacier terminus, community complexity increased via sequential occurrences of cyanobacteria, diatoms, invertebrates, and vertebrates, as well as increasing taxa numbers. The stream and lake showed different community compositions and distinct taxa. Furthermore, the correlations with environmental factors and community assembly mechanisms showed group- and habitat-specific patterns. Our results reveal the rapid spatial succession and increasing community complexity along glacial flowpaths and highlight the varying adaptivity of different organisms, while also providing insight into the ecosystem responses to global change.

Protopanaxadiols Eliminate Behavioral Impairments and Mitochondrial Dysfunction in Parkinson's Disease Mice Model.

Currently, there are no effective therapies to cure Parkinson's disease (PD), which is the second most common neurodegenerative disease primarily characterized by motor dysfunction and degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc). Protopanaxadiols (PPDs), including 20 (R)- protopanaxadiol (R-PPD) and 20 (S)- protopanaxadiol (S-PPD), are main metabolites of ginsenosides. The role of ginsenosides in neurodegenerative diseases has been thoroughly studied, however, it is unknown whether PPDs can attenuate behavioral deficits and dopaminergic neuron injury in PD model mice to date. Here, we administered PPDs to MPTP-induced PD model mice and monitored the effects on behavior and dopaminergic neurons to investigate the effects of R-PPD and S-PPD against PD. Our results showed that R-PPD and S-PPD (at a dose of 20 mg/kg, i.g.) treatment alleviated MPTP (30 mg/kg, i.p.) induced behavioral deficits. Besides, R-PPD and S-PPD protected MPP+-induced neuron injury and mitochondrial dysfunction, and reduced the abnormal expression of Cyt C, Bax, caspase-3 and Bcl-2. These findings demonstrate that R-PPD and S-PPD were potentially useful to ameliorate PD.

STUB1 increases adiponectin expression by inducing ubiquitination and degradation of NR2F2, thereby reducing hepatic stellate cell activation and alleviating non-alcoholic fatty liver disease.

BACKGROUND: Adiponectin (APN) has exhibited ameliorating effects on non-alcoholic fatty liver disease (NAFLD). This study investigates the roles of APN and its regulatory molecules in hepatic stellate cell (HSC) activation and the progression of NAFLD. METHODS: Mice were subjected to a high-fat diet (HFD) to establish NAFLD models. Liver tissue was examined for lipid metabolism, fibrosis, and inflammation. Mouse 3T3-L1 adipocytes were exposed to palmitic acid (PA) to mimic a high-fat environment. The conditioned medium (CM) from adipocytes was collected for the culture of isolated mouse HSCs. Gain- or loss-of-function studies of APN, nuclear receptor subfamily 2 group F member 2 (NR2F2), and STIP1 homology and U-box containing protein 1 (STUB1) were performed to analyze their roles in NAFLD and HSC activation in vivo and in vitro. RESULTS: APN expression was poorly expressed in HFD-fed mice and PA-treated 3T3-L1 adipocytes, which was attributed to the transcription inhibition mediated by NR2F2. Silencing of NR2F2 restored the APN expression, ameliorating liver steatosis, fibrosis, and inflammatory cytokine infiltration in mouse livers and reducing HSC activation. Similarly, the NR2F2 silencing condition reduced HSC activation in vitro. However, these effects were counteracted by artificial APN silencing. STUB1 facilitated the ubiquitination and protein degradation of NR2F2, and its upregulation mitigated NAFLD-like symptoms in mice and HSC activation, effects reversed by the NR2F2 overexpression. CONCLUSION: This study highlights the role of STUB1 in reducing HSC activation and alleviating NAFLD by attenuating NR2F2-mediated transcriptional repression of APN.

Analyzing the factors associated with efficacy among teriparatide treatment in postmenopausal women with osteoporosis.

BACKGROUND: Teriparatide (TPTD) is a widely used anabolic agent for the treatment of osteoporosis. Several factors have been identified to be related to bone mineral density (BMD) increase in anti-osteoporosis treatment with other agents; however, there has been no systematic analysis to summarize the associated determinants of BMD reaction to daily teriparatide treatment. METHODS: In this retrospective study, we performed a comprehensive investigation involving not only clinical data but also several relevant lifestyle factors to be examined for their potential contribution to BMD response. This post-hoc analysis included 258 post-menopaused patients with osteoporosis who received TPTD at 20 µg/day for 12 months. Univariate and multivariate analyses were conducted to distinguish the response variables of lumbar spine (LS) BMD transformation, the principal outcome measure of efficacy, from the baseline at 12 months. RESULTS: Twelve months of TPTD treatment resulted in an absolute 0.39 ± 0.37 increase in T-score of LS BMD. Gastrointestinal disease, prior bisphosphonate or glucocorticoid treatment, no vitamin K2 supplementation, low levels of serum 25(OH)D and PINP, weak increment of PINP and ß-CTX at 3 months, unhealthy lifestyle (excessive smoking, tea, coffee, and drinking), vegetarian diet pattern, low ALT level, and high BMD at baseline were determined by univariate analyses to be related to the weak reaction of TPTD treatment (P < 0.10). In the multiple regression model, postmenopausal women with vitamin K2 supplementation, higher baseline serum 25(OH)D level, and higher PINP concentration at 3 months indicated a good reaction of LS BMD at 12 months (P < 0.05). Patients with gastrointestinal disease, prior bisphosphonate and glucocorticoid treatment, vegetarian diet pattern, and higher baseline BMD were significantly more likely to have a lower absolute LS BMD response compared to patients without these characteristics (P < 0.05). Further analysis confirmed the negative effect of unhealthy lifestyle on TPTD treatment. CONCLUSION: Our results emphasize the significance of a comprehensive assessment of clinical or lifestyle-related characteristics of postmenopausal women with osteoporosis in the management of TPTD therapy in routine care.

The Role of Calcium and Iron Homeostasis in Parkinson's Disease.

Calcium and iron are essential elements that regulate many important processes of eukaryotic cells. Failure to maintain homeostasis of calcium and iron causes cell dysfunction or even death. PD (Parkinson's disease) is the second most common neurological disorder in humans, for which there are currently no viable treatment options or effective strategies to cure and delay progression. Pathological hallmarks of PD, such as dopaminergic neuronal death and intracellular α-synuclein deposition, are closely involved in perturbations of iron and calcium homeostasis and accumulation. Here, we summarize the mechanisms by which Ca2+ signaling influences or promotes PD progression and the main mechanisms involved in ferroptosis in Parkinson's disease. Understanding the mechanisms by which calcium and iron imbalances contribute to the progression of this disease is critical to developing effective treatments to combat this devastating neurological disorder.

Deciphering the structure, function, and mechanism of lysine acetyltransferase cGNAT2 in cyanobacteria.

Lysine acetylation is a conserved regulatory posttranslational protein modification that is performed by lysine acetyltransferases (KATs). By catalyzing the transfer of acetyl groups to substrate proteins, KATs play critical regulatory roles in all domains of life; however, no KATs have yet been identified in cyanobacteria. Here, we tested all predicted KATs in the cyanobacterium Synechococcus sp. PCC 7002 (Syn7002) and demonstrated that A1596, which we named cyanobacterial Gcn5-related N-acetyltransferase (cGNAT2), can catalyze lysine acetylation in vivo and in vitro. Eight amino acid residues were identified as the key residues in the putative active site of cGNAT2, as indicated by structural simulation and site-directed mutagenesis. The loss of cGNAT2 altered both growth and photosynthetic electron transport in Syn7002. In addition, quantitative analysis of the lysine acetylome identified 548 endogenous substrates of cGNAT2 in Syn7002. We further demonstrated that cGNAT2 can acetylate NAD(P)H dehydrogenase J (NdhJ) in vivo and in vitro, with the inability to acetylate K89 residues, thus decreasing NdhJ activity and affecting both growth and electron transport in Syn7002. In summary, this study identified a KAT in cyanobacteria and revealed that cGNAT2 regulates growth and photosynthesis in Syn7002 through an acetylation-mediated mechanism.

The effects of Danzhi Jiangtang capsule on clinical indices and vascular endothelial function in patients with impaired glucose tolerance of Qi-Yin deficiency type.

OBJECTIVE: To observe the effect of Danzhi Jiangtang capsule (DJC) on the clinical indexes and vascular endothelial function indexes in patients with impaired glucose tolerance (IGT). METHODS: A total of 106 patients were enrolled and randomly assigned to the treatment group and control group following a four-week washout period. The patients in the control group received a general lifestyle intervention, while those in the treatment group received DJC (2.0 g 3× a day) in conjunction with the intervention given to the control group patients. The physiological and biochemical levels, vascular endothelial function indices, and traditional Chinese medicine (TCM) syndrome ratings of the patients in the two groups were compared after 12 weeks of therapy. RESULTS: In the control group, the diastolic blood pressure (DBP) was significantly improved compared with those before treatment (83.31 ± 6.47 vs. 79.21 ± 6.17, p < .01) (CI: 1.45, 6.73; Cohen's d: 10.51), as was the case with the nitric oxide (NO) levels and TCM syndrome points (35.71 ± 4.58 vs. 43.96 ± 5.17, 9.57 ± 2.63 vs. 5.38 ± 1.79, p < .001) (CI: -10.28, -6.24; 3.12, 5.18; Cohen's d: 0.90). In the treatment group, the levels of fasting blood glucose, endothelin and vascular endothelial growth factor were significantly improved compared with control group (4.92 ± 0.21 vs. 5.59 ± 0.31, 59.37 ± 13.25 vs. 72.13 ± 12.37, 19.25 ± 2.80 vs. 26.76 ± 1.88, p < .001) (CI: 0.55, 0.78; 7.40, 18.13; 6.52, 8.50; Cohen's d: 4.94, 0.41, 1.32), as was the case with 2-h post-load plasma glucose and total cholesterol (TC) (8.33 ± 0.62 vs. 8.89 ± 1.55, 4.61 ± 1.05 vs. 5.22 ± 1.12, p < .05) (CI: 0.07, 1.07; 0.15, 1.06; Cohen's d: 0.40, 0.51). CONCLUSIONS: Treatment with DJC could significantly improve the physiological and biochemical indicators, vascular endothelial function, and TCM syndrome points of IGT patients, indicating that DJC could be a potential drug to treat patients with IGT of Qi-Yin deficiency type.

PatU3 plays a central role in coordinating cell division and differentiation in pattern formation of filamentous cyanobacterium Nostoc sp. PCC 7120.

Spatial periodic signal for cell differentiation in some multicellular organisms is generated according to Turing's principle for pattern formation. How a dividing cell responds to the signal of differentiation is addressed with the filamentous cyanobacterium Nostoc sp. PCC 7120, which forms the patterned distribution of heterocysts. We show that differentiation of a dividing cell was delayed until its division was completed and only one daughter cell became heterocyst. A mutant of patU3, which encodes an inhibitor of heterocyst formation, showed no such delay and formed heterocyst pairs from the daughter cells of cell division or dumbbell-shaped heterocysts from the cells undergoing cytokinesis. The patA mutant, which forms heterocysts only at the filament ends, restored intercalary heterocysts by a single nucleotide mutation of patU3, and double mutants of patU3/patA and patU3/hetF had the phenotypes of the patU3 mutant. We provide evidence that HetF, which can degrade PatU3, is recruited to cell divisome through its C-terminal domain. A HetF mutant with its N-terminal peptidase domain but lacking the C-terminal domain could not prevent the formation of heterocyst pairs, suggesting that the divisome recruitment of HetF is needed to sequester HetF for the delay of differentiation in dividing cells. Our study demonstrates that PatU3 plays a key role in cell-division coupled control of differentiation.

Cryo-EM and femtosecond spectroscopic studies provide mechanistic insight into the energy transfer in CpcL-phycobilisomes.

Phycobilisomes (PBS) are the major light harvesting complexes of photosynthesis in the cyanobacteria and red algae. CpcL-PBS is a type of small PBS in cyanobacteria that transfers energy directly to photosystem I without the core structure. Here we report the cryo-EM structure of the CpcL-PBS from the cyanobacterium Synechocystis sp. PCC 6803 at 2.6-Å resolution. The structure shows the CpcD domain of ferredoxin: NADP+ oxidoreductase is located at the distal end of CpcL-PBS, responsible for its attachment to PBS. With the evidence of ultrafast transient absorption and fluorescence spectroscopy, the roles of individual bilins in energy transfer are revealed. The bilin 1Iß822 located near photosystem I has an enhanced planarity and is the red-bilin responsible for the direct energy transfer to photosystem I.

Pneu-HTP based extrusion actuation in bio-inspired soft joint.

Inspired by the joint structure and actuation mechanism of spider legs, a novel pneumatic soft joint actuator is designed, which achieves joint rotation by mutual compression of two hyperelastic sidewalls under inflation pressure. For this type of extrusion actuation, a pneumatic hyperelastic thin plate (Pneu-HTP) based actuation modeling method is proposed. The two actuating surfaces extruded mutually of the actuator are considered as Pneu-HTPs, and mathematical models for their parallel extrusion actuation and angular extrusion actuation are derived. The finite element analysis (FEA) simulations and experiments were also performed to evaluate the model accuracy of the Pneu-HTP extrusion actuation. The results for the parallel extrusion actuation show that the average relative error between the proposed model and the experiment is only 9.27%, and the goodness-of-fit is greater than 99%. For the angular extrusion actuation, the average relative error between the model and the experiment is 12.5%, and the goodness-of-fit is greater than 99%. The parallel extrusion actuating force and rotational extrusion actuating force of the Pneu-HTP are also highly consistent with the FEA simulation results, which provides a promising method for the accurate modeling of extrusion actuation in soft actuator.

Urban landscape-level biodiversity assessments of aquatic and terrestrial vertebrates by environmental DNA metabarcoding.

Globally, expansive urbanization profoundly alters natural habitats and the associated biota. Monitoring biodiversity in cities can provide essential information for conservation management, but the complexity of urban landscapes poses serious challenges to conventional observational and capture-based surveys. Here we assessed pan-vertebrate biodiversity, including both aquatic and terrestrial taxa, using environmental DNA (eDNA) sampled from 109 water sites across Beijing, China. Using eDNA metabarcoding with a single primer set (Tele02), we detected 126 vertebrate species, including 73 fish, 39 birds, 11 mammals, and 3 reptiles belonging to 91 genera, 46 families, and 22 orders. The probability of detection from eDNA varied substantially among species and was related to their lifestyle, as shown by the greater detectability of fish compared to that of terrestrial and arboreal (birds and mammals) groups, as well as the greater detectability of water birds compared to that of forest birds (Wilcoxon rank-sum test p = 0.007). Furthermore, the eDNA detection probabilities across all vertebrates (Wilcoxon rank-sum test p = 0.009), as well as for birds (p < 0.001), were higher at lentic sites in comparison with lotic sites. Also, the detected biodiversity was positively correlated with lentic waterbody size for fish (Spearman p = 0.012), but not for other groups. Our results demonstrate the capacity of eDNA metabarcoding to efficiently surveil diverse vertebrate communities across an extensive spatial scale in heterogenous urban landscapes. With further methodological development and optimization, the eDNA approach has great potential for non-invasive, efficient, economic, and timely assessments of biodiversity responses to urbanization, thus guiding city ecosystem conservation management.

Characterization of gut microbial and metabolite alterations in faeces of Goto Kakizaki rats using metagenomic and untargeted metabolomic approach.

BACKGROUND: In recent years, the incidence of type 2 diabetes (T2DM) has shown a rapid growth trend. Goto Kakizaki (GK) rats are a valuable model for the study of T2DM and share common glucose metabolism features with human T2DM patients. A series of studies have indicated that T2DM is associated with the gut microbiota composition and gut metabolites. We aimed to systematically characterize the faecal gut microbes and metabolites of GK rats and analyse the relationship between glucose and insulin resistance. AIM: To evaluate the gut microbial and metabolite alterations in GK rat faeces based on metagenomics and untargeted metabolomics. METHODS: Ten GK rats (model group) and Wistar rats (control group) were observed for 10 wk, and various glucose-related indexes, mainly including weight, fasting blood glucose (FBG) and insulin levels, homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of ß cell (HOMA-ß) were assessed. The faecal gut microbiota was sequenced by metagenomics, and faecal metabolites were analysed by untargeted metabolomics. Multiple metabolic pathways were evaluated based on the differential metabolites identified, and the correlations between blood glucose and the gut microbiota and metabolites were analysed. RESULTS: The model group displayed significant differences in weight, FBG and insulin levels, HOMA-IR and HOMA-ß indexes (P < 0.05, P < 0.01) and a shift in the gut microbiota structure compared with the control group. The results demonstrated significantly decreased abundances of Prevotella sp. CAG:604 and Lactobacillus murinus (P < 0.05) and a significantly increased abundance of Allobaculum stercoricanis (P < 0.01) in the model group. A correlation analysis indicated that FBG and HOMA-IR were positively correlated with Allobaculum stercoricanis and negatively correlated with Lactobacillus murinus. An orthogonal partial least squares discriminant analysis suggested that the faecal metabolic profiles differed between the model and control groups. Fourteen potential metabolic biomarkers, including glycochenodeoxycholic acid, uric acid, 13(S)-hydroxyoctadecadienoic acid (HODE), N-acetylaspartate, ß-sitostenone, sphinganine, 4-pyridoxic acid, and linoleic acid, were identified. Moreover, FBG and HOMA-IR were found to be positively correlated with glutathione, 13(S)-HODE, uric acid, 4-pyridoxic acid and allantoic acid and ne-gatively correlated with 3-α, 7-α, chenodeoxycholic acid glycine conjugate and 26-trihydroxy-5-ß-cholestane (P < 0.05, P < 0.01). Allobaculum stercoricanis was positively correlated with linoleic acid and sphinganine (P < 0.01), and 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate was negatively associated with Prevotella sp. CAG:604 (P < 0.01). The metabolic pathways showing the largest differences were arginine biosynthesis; primary bile acid biosynthesis; purine metabolism; linoleic acid metabolism; alanine, aspartate and glutamate metabolism; and nitrogen metabolism. CONCLUSION: Metagenomics and untargeted metabolomics indicated that disordered compositions of gut microbes and metabolites may be common defects in GK rats.

Application of machine learning in Chinese medicine differentiation of dampness-heat pattern in patients with type 2 diabetes mellitus.

Background: China has become the country with the largest number of people with type 2 diabetes mellitus (T2DM), and Chinese medicine (CM) has unique advantages in preventing and treating T2DM, while accurate pattern differentiation is the guarantee for proper treatment. Objective: The establishment of the CM pattern differentiation model of T2DM is helpful to the pattern diagnosis of the disease. At present, there are few studies on dampness-heat pattern differentiation models of T2DM. Therefore, we establish a machine learning model, hoping to provide an efficient tool for the pattern diagnosis of CM for T2DM in the future. Methods: A total of 1021 effective samples of T2DM patients from ten CM hospitals or clinics were collected by a questionnaire including patients' demographic and dampness-heat-related symptoms and signs. All information and the diagnosis of the dampness-heat pattern of patients were completed by experienced CM physicians at each visit. We applied six machine learning algorithms (Artificial Neural Network [ANN], K-Nearest Neighbor [KNN], Naïve Bayes [NB], Support Vector Machine [SVM], Extreme Gradient Boosting [XGBoost] and Random Forest [RF]) and compared their performance. And then we also utilized Shapley additive explanation (SHAP) method to explain the best performance model. Results: The XGBoost model had the highest AUC (0.951, 95% CI 0.925-0.978) among the six models, with the best sensitivity, accuracy, F1 score, negative predictive value, and excellent specificity, precision, and positive predictive value. The SHAP method based on XGBoost showed that slimy yellow tongue fur was the most important sign in dampness-heat pattern diagnosis. The slippery pulse or rapid-slippery pulse, sticky stool with ungratifying defecation also performed an important role in this diagnostic model. Furthermore, the red tongue acted as an important tongue sign for the dampness-heat pattern. Conclusion: This study constructed a dampness-heat pattern differentiation model of T2DM based on machine learning. The XGBoost model is a tool with the potential to help CM practitioners make quick diagnosis decisions and contribute to the standardization and international application of CM patterns.

Mutagenic analysis of the bundle-shaped phycobilisome from Gloeobacter violaceus.

Gloeobacter violaceus is an ancient cyanobacterium as it branches out from the basal position in the phylogenic tree of cyanobacteria. It lacks thylakoid membranes and its unique bundle-shaped type of phycobilisomes (PBS) for light harvesting in photosynthesis are located on the interior side of cytoplasmic membranes. The PBS from G. violaceus have two large linker proteins that are not present in any other PBS, Glr2806, and Glr1262, which are encoded by the genes glr2806 and glr1262, respectively. The location and functions of the linkers Glr2806 and Glr1262 are currently unclear. Here, we report the studies of mutagenetic analysis of glr2806 and the genes of cpeBA, encoding the ß and α subunits of phycoerythrin (PE), respectively. In the mutant lacking glr2806, the length of the PBS rods remains unchanged, but the bundles are less tightly packed as examined by electron microscopy with negative staining. It is also shown that two hexamers are missing in the peripheral area of the PBS core, strongly suggesting that the linker Glr2806 is located in the core area instead of the rods. In the mutant lacking the cpeBA genes, PE is no longer present and the PBS rods have only three layers of phycocyanin hexamers. The construction of deletional mutants in G. violaceus, achieved for the first time, provides critical information for our understanding of its unique PBS and should be useful in studies of other aspects of this interesting organism as well.

To the north: eDNA tracing of the seasonal and spatial dynamics of fish assemblages along the world's largest water diversion project.

Extensive water diversion projects that have been increasingly installed worldwide transport essential water resources as well as a large number of biota. However, studies of the dynamic processes of such transport have been limited. The South-to-North Water Diversion Project of China is the largest manmade water diversion system ever constructed. Here, in a year-long project, we used environmental DNA (eDNA) metabarcoding to assess fish biodiversity and assemblage composition along the Project's 1277-km main canal, while also investigating the temporal, spatial, and functional trait drivers of changes in the fish assemblages. Together, 45 fish taxa were detected, with substantial compositional variations between seasons. The number of detected species typically dropped upon entering the canal but remained relatively constant along the canal's length. Spatial variations in fish assemblages were generally dominated by the turnover component over nestedness, and a positive spatial autocorrelation of qualitative assemblage composition was detected within 80 km in all seasons. Furthermore, several functional traits, such as smaller body size, invertivorous diet, rheophilic living, and lithophilic and demersal spawning, were positive predictors of fish presence along the length of the canal and they may boost species chances of introduction to the recipient areas. Our results provide crucial information for ecological management of diversion projects and have key implications for modelling and predicting foreign species invasion through water transfers.

Multi-group biodiversity distributions and drivers of metacommunity organization along a glacial-fluvial-limnic pathway on the Tibetan plateau.

Extensive global glacial retreats are threatening cryosphere ecosystem functioning and the associated biota in glacier-fed water systems. Understanding multi-group biodiversity distributions and compositional variation across diverse but hydrologically linked habitats under varying glacial influences will help explain the mechanisms underlying glacial community organization and ecosystem processes. However, such data are generally lacking due to the difficulty of obtaining biodiversity information across wide taxonomic ranges. Here, we used a multi-marker environmental DNA metabarcoding approach to simultaneously investigate the spatial patterns of community compositions and assembly mechanisms of four taxonomic groups (cyanobacteria, diatoms, invertebrates, and vertebrates) along the flowpaths of a tributary of Lake Nam Co on the Tibetan Plateau-from its glacier headwaters, through its downstream river and wetlands, to its estuary. We detected 869 operational taxonomic units: 119 cyanobacterial, 395 diatom, 269 invertebrate, and 86 vertebrate. Taxonomic richnesses consistently increased from upstream to downstream, and although all groups showed community similarity distance decay patterns, the trend for vertebrates was the weakest. Cyanobacteria, diatom, and invertebrate community compositions were significantly correlated with several environmental factors, while the vertebrate community was only correlated with waterway width. Variation partitioning analysis indicated that varying extents of environmental conditions and spatial factors affected community organizations for different groups. Furthermore, stochastic processes contributed prominently to the microorganisms' community assembly (Sloan's neutral model R2 = 0.77 for cyanobacteria and 0.73 for diatoms) but were less important for macroorganisms (R2 = 0.21 for invertebrates and 0.15 for vertebrates). That trend was further substantiated by modified stochasticity ratio analyses. This study provides the first holistic picture of the diverse biotic communities residing in a series of hydrologically connected glacier-influenced habitats. Our results both uncovered the distinct mechanisms that underlie the metacommunity organizations of different glacial organisms and helped comprehensively predict the ecological impacts of the world's melting glaciers.

Food webs reveal coexistence mechanisms and community organization in carnivores.

Globally, massive carnivore guild extirpations have led to trophic downgrading and compromised ecosystem services. However, the complexity of multi-carnivore food webs complicates accurate identification of species interactions and community organization. Here, we used fecal DNA metabarcoding to investigate three communities that together encompass eight large- and meso-carnivore species and their 44 prey taxa of the Qinghai-Tibet Plateau (QTP), one of the last places on Earth that still harbors intact carnivore assemblages. Quantitative food-web analyses revealed pronounced interspecific variations in the carnivores' prey compositions and dietary partitioning both between and within guilds. Additionally, body masses of the carnivores and their prey exhibited consistent hump-shaped correlations across communities. Overall, differences in prey diversity, size category, and proportional utilization among the carnivore species result in trophic niche segregation that likely promotes carnivore coexistence in the harsh QTP environment. Network structure analyses detected significant modularity in all food webs but nestedness in only one. Furthermore, network characterization identified pikas (Ochotona spp.), bharal (Pseudois nayaur), and domestic yak (Bos grunniens) as potential keystone prey across the areas. Our results paint a holistic and detailed picture of the QTP carnivore assemblages' trophic networks and demonstrate that the combined use of the molecular dietary approach and network analysis can generate structural insights into carnivore coexistence and can identify functionally important species in complex communities. Such knowledge can help safeguard carnivore guild integrity and enhance community resilience to environmental perturbations in the sensitive QTP ecosystems.

Association between short-term exposure to extreme humidity and painful diabetic neuropathy: a case-crossover analysis.

Painful diabetic neuropathy (PDN) is a common complication of diabetes mellitus, which reduces the quality of life. However, the association between PDN and environmental factors, especially ambient humidity, remains unclear. Therefore, this study investigated the impact of extreme humidity events on PDN. Data on PDN-related hospital admissions to two tertiary hospitals in Hefei, China (2014-2019) were obtained. A distributed lag non-linear model with a case-crossover design was used to quantitatively estimate the effects of ambient humidity on PDN, and the results were stratified by sex and age. The 1st, 10th, 90th, and 99th percentiles of relative humidity (RHU) were defined as extreme humidity, and the average relative humidity (74.94%) was set as the reference value. Non-linear exposure-response curves between the RHU and PDN cases were obtained. Extreme humidity (92%) had a significant effect on PDN with a relative risk (RR) of 1.13 (95% confidence interval (CI): 1.01-1.26) on a particular day, which increased with the RHU (RR: 1.21, 95% CI: 1.02-1.45 at 98% extreme humidity). Stratification analysis showed that women (RR: 1.38, 95% CI: 1.07-1.77) and patients aged < 65 years (RR: 1.26, 95% CI: 1.01-1.57) were highly susceptible to this effect on the same day. The results suggest that extreme humidity is a crucial trigger for PDN onset in diabetes patients. Furthermore, the effects vary with sex and age. This study provides detailed evidence of the adverse effects of extreme weather on diabetes patients.