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Context Measurement of plasma steroids is necessary for diagnosis of congenital adrenal hyperplasia (CAH). We sought to establish an efficient strategy for detection and subtyping of CAH with a machine-learning algorithm. Methods Clinical phenotype and genetic testing were used to provide CAH diagnosis and subtype. We profiled 13 major steroid hormones by liquid chromatography-tandem mass spectrometry. A multiclassifier system was established to distinguish 11β-hydroxylase deficiency (11βOHD), 17α-hydroxylase/17,20-lyase deficiency (17OHD), and 21α-hydroxylase deficiency (21OHD) in a discovery cohort (n = 226). It was then validated in an independent cohort (n = 111) and finally applied in a perspective cohort of 256 patients. The diagnostic performance on the basis of area under receiver operating characteristic curves (AUCs) was evaluated. Results A cascade logistic regression model, we named the “Steroidogenesis Score”, was able to discriminate the 3 most common CAH subtypes: 11βOHD, 17OHD, and 21OHD. In the perspective application cohort, the steroidogenesis score had a high diagnostic accuracy for all 3 subtypes, 11βOHD (AUC, 0.994; 95% CI, 0.983-1.000), 17OHD (AUC, 0.993; 95% CI, 0.985-1.000), and 21OHD (AUC, 0.979; 95% CI, 0.964-0.994). For nonclassic 21OHD patients, the tool presented with significantly higher sensitivity compared with measurement of basal 17α-hydroxyprogesterone (17OHP) (0.973 vs 0.840, P = 0.005) and was not inferior to measurement of basal vs stimulated 17OHP (0.973 vs 0.947, P = 0.681). Conclusions The steroidogenesis score was biochemically interpretable and showed high accuracy in identifying CAH patients, especially for nonclassic 21OHD patients, thus offering a standardized approach to diagnose and subtype CAH.

MELAS (mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes) is a progressive neurodegenerative disease caused by pathogenic mitochondrial DNA variants. The pathogenic mechanism of MELAS remains enigmatic due to the exceptional clinical heterogeneity and the obscure genotype-phenotype correlation among MELAS patients. To gain insights into the pathogenic signature of MELAS, we designed a comprehensive strategy integrating proteomics and metabolomics in patient-derived dermal fibroblasts harboring the ultra-rare MELAS pathogenic variant m.14453G>A, specifically affecting the mitochondrial respiratory Complex I. Global proteomics was achieved by data-dependent acquisition (DDA) and verified by data-independent acquisition (DIA) using both Spectronaut and the recently launched MaxDIA platforms. Comprehensive metabolite coverage was achieved for both polar and nonpolar metabolites in both reverse phase and HILIC LC-MS/MS analyses. Our proof-of-principle MELAS study with multi-omics integration revealed OXPHOS dysregulation with a predominant deficiency of Complex I subunits, as well as alterations in key bioenergetic pathways, glycolysis, tricarboxylic acid cycle, and fatty acid β-oxidation. The most clinically relevant discovery is the downregulation of the arginine biosynthesis pathway, likely due to blocked argininosuccinate synthase, which is congruent with the MELAS cardinal symptom of stroke-like episodes and its current treatment by arginine infusion. In conclusion, we demonstrated an integrated proteomic and metabolomic strategy for patient-derived fibroblasts, which has great clinical potential to discover therapeutic targets and design personalized interventions after validation with a larger patient cohort in the future.Abstract FigureGraphic Abstract:Integrated proteomics and metabolomics of patient fibroblasts revealed dysregulations in arginine biosynthesis, OXPHOS complexes, and bioenergetic pathways in MELAS, a mitochondrial neurodegenerative disease caused by mitochondrial DNA mutations.

The ladybird beetle Henosepilachna vigintioctomaculata is an economically significant oligophagous pest that induces damage to many Solanaceae crops. An increasing number of studies have examined the population and phenotype diversity of ladybird beetles. However, few comparative genome analyses of ladybird beetle species have been conducted. Here, we obtained a high-quality chromosome-level genome assembly of H. vigintioctomaculata using various sequencing technologies, and the chromosome-level genome assembly was ~581.63 Mb, with 11 chromosomes successfully assembled. The phylogenetic analysis showed that H. vigintioctomaculata is a more ancient lineage than the other three sequenced ladybird beetles, Harmonia axyridis, Propylea japonica, and Coccinella septempunctata. We also compared positively selected genes (PSGs), transposable elements (TEs) ratios and insertion times, and key gene families associated with environmental adaptation among these ladybird beetles. The pattern of TEs evolution of H. vigintioctomaculata differs from the other three ladybird beetles. The PSGs were associated with ladybird beetles development. However, the key gene families associated with environmental adaptation in ladybird beetles varied. Overall, the high-quality draft genome sequence of H. vigintioctomaculata provides a useful resource for studies of beetle biology, especially for the invasive biology of ladybird beetles.

The Amazon sailfin catfish (Pterygoplichthys pardalis), which belongs to the Loricariidae family, is an invasive species that has caused massive damage to the ecological environment. However, a high-quality reference genome for this catfish species has not yet been reported. Here, we successfully assembled the first chromosome-level high-quality genome of P. pardalis using data produced from multiple sequencing platforms. The assembled genome contains 26 chromosomes, with a scaffold N50 of 49.47 Mb. Different evaluation methods indicated the high connectivity and accuracy genome we got. In total, 23 859 protein-coding genes were predicted in the genome, 22 169 (92.92%) of which were functionally annotated in public databases. Phylogenetic analysis showed that P. pardalis was clustered with all other catfish studied and diverged from their common ancestor 132.5 million years ago. Whole-genome collinearity analysis indicated the chromosome 6 of P. pardalis was aligned to two distinct chromosomes in Ameiurus melas, Pangasianodon hypophthalmus, and Ictalurus punctatus, suggesting the occurrence of potential chromosomal fusion/fission events. Furthermore, many immune system-related genes were expanded in the P. pardalis genome, which may have contributed to their adaptive traits to highly polluted environments and successful invasion. This study not only provides insights into the genetic basis of the successful invasion of P. pardalis, but also provides important data for comparative genomic analysis of P. pardalis in Siluriformes in the future.

Brachymystax tsinlingensis Li, 1966 is an endangered freshwater fish with economic, ecological, and scientific values. Study of the genome of B. tsinlingensis might be particularly insightful given that this is the only Brachymystax species with genome. We present a high-quality chromosome-level genome assembly and protein-coding gene annotation for B. tsinlingensis with Illumina short reads, Nanopore long reads, Hi-C sequencing reads, and RNA-seq reads from 5 tissues/organs. The final chromosome-level genome size is 2,031,709,341 bp with 40 chromosomes. We found that the salmonids have a unique GC content and codon usage, have a slower evolutionary rate, and possess specific positively selected genes. We also confirmed the salmonids have undergone a whole-genome duplication event and a burst of transposon-mediated repeat expansion, and lost HoxAbβ Hox cluster, highly expressed genes in muscle may partially explain the migratory habits of B. tsinlingensis. The high-quality B. tsinlingensis assembled genome could provide a valuable reference for the study of other salmonids as well as aid the conservation of this endangered species.

Protein biotinylation via chemical or enzymatic reactions is often coupled with streptavidin-based enrichment and on-bead digestion in numerous biological applications. However, the popular on-bead digestion method faces major challenges of streptavidin contamination, overwhelming signals from endogenous biotinylated proteins, the lost information on biotinylation sites, and limited sequence coverage of enriched proteins. Here, we explored thiol-cleavable biotin as an alternative approach to elute biotinylated proteins from streptavidin-coated beads for both chemical biotinylation and biotin ligase-based proximity labeling. All possible amino acid sites for biotinylation were thoroughly evaluated in addition to the primary lysine residue. We found that biotinylation at lysine residues notably reduces the trypsin digestion efficiency, which can be mitigated by the thiol-cleavable biotinylation method. We then evaluated the applicability of thiol-cleavable biotin as a substrate for proximity labeling in living cells, where TurboID biotin ligase was engineered onto the mitochondrial inner membrane facing the mitochondrial matrix. As a proof-of-principle study, thiol-cleavable biotin-assisted TurboID proteomics achieved remarkable intraorganelle spatial resolution with significantly enriched proteins localized in the mitochondrial inner membrane and mitochondrial matrix.

The Atlantic sea nettle ( Chrysaora quinquecirrha) has an important evolutionary position due to its high ecological value. However, due to limited sequencing technologies and complex jellyfish genomic sequences, the current C. quinquecirrha genome assembly is highly fragmented. Here, we used the most advanced high-throughput chromosome conformation capture (Hi-C) technology to obtain high-coverage sequencing data of the C. quinquecirrha genome. We then anchored these data to the previously published contig-level assembly to improve the genome. Finally, a high-continuity genome sequence of C. quinquecirrha was successfully assembled, which contained 1 882 scaffolds with a N50 length of 3.83 Mb. The N50 length of the genome assembly was 5.23 times longer than the previously released one, and additional analysis revealed that it had a high degree of genomic continuity and accuracy. Acquisition of the high-continuity genome sequence of C. quinquecirrha not only provides a basis for the study of jellyfish evolution through comparative genomics but also provides an important resource for studies on jellyfish growth and development.

Introduction East Asians are more susceptible to early-onset diabetes than Europeans and exhibit reduced insulin secretion at earlier stages. PAX4 plays a critical role in the development of β-cells. The dysfunction-missense variants PAX4 R192H and PAX4 R192S are common in East Asians but rare in Europeans. Therefore, we aim to investigate the diabetes-associated genes, including PAX4 R192H/S, in East Asians with early-onset diabetes. Methods Exome variants of 80 Chinese early-onset diabetes patients (onset age

The blue king crab, Paralithodes platypus, which belongs to the family Lithodidae, is a commercially and ecologically important species. However, a high‐quality reference genome for the king crab has not yet been reported. Here, we assembled the first chromosome‐level blue king crab genome, which contains 104 chromosomes and an N50 length of 51.15 Mb. Furthermore, we determined that the large genome size can be attributed to the insertion of long interspersed nuclear elements and long tandem repeats. Genome assembly assessment showed that 96.54% of the assembled transcripts could be aligned to the assembled genome. Phylogenetic analysis showed the blue king crab to have a close relationship with the Eubrachyura crabs, from which it diverged 272.5 million years ago. Population history analyses indicated that the effective population of the blue king crab declined sharply and then gradually increased from the Cretaceous and Neogene periods, respectively. Furthermore, gene families related to developmental pathways, steroid and thyroid hormone synthesis, and inflammatory regulation were expanded in the genome, suggesting that these genes contributed substantially to the environmental adaptation and unique body plan evolution of the blue king crab. The high‐quality reference genome reported here provides a solid molecular basis for further study of the blue king crab's development and environmental adaptation.

Mild thyroid peroxidase (TPO) deficiency is rare and can be extremely occult. This study aimed to replenish the phenotypic and genetic spectrum of mild TPO deficiency. Four unrelated patients with progressive goiter were described in this study. Genes associated with congenital hypothyroidism were analyzed and in vitro functional experiments were conducted to evaluate the residual TPO enzyme activities of each mutant. The four patients (age: 5–27 years old) were characterized by progressive goiter, discordant alteration in thyroid hormones with free triiodothyronine (FT3) to free thyroxine (FT4) ratio ranging from 0.557 to 1.012, two with slightly elevated TSH level and two with normal TSH level. Six different mutations of TPO gene were identified including three novel mutations (p.Glu337Lys, p.Ala544Val, and p.Glu641Lysfs∗21). Two mutants (p.Asp224del and p.Ala544Val) with residual TPO activity of 41 and 65% may explain the mild TPO-deficient picture in our study. After levothyroxine (L-T4) therapy, three patients showed gradual decline of FT3 to FT4 ratio and two patients showed reduced thyroid size. Patients with mild TPO deficiency can present with progressive goiter, normal TSH level, and largely reserved TPO activities.

Gobiocypris rarus is sensitive to environmental pollution, especially to heavy metal and grass carp reovirus (GCRV). Hence, it has potential utility as a biological monitor. Genetic deciphering of its unique immune system will advance our understanding of its unique adaptive strategies, which provide cues for its better application. A de novo genome of rare minnow was obtained, and its sex determination mechanism is ZZ/ZW. We identified several specific mutation genes and specific lost genes of rare minnow, and these might be related to the sensitivity of rare minnow to environmental stimuli. We also analyzed the gene expression level of different organs/tissues and found that several IFIT genes may play key roles in GCRV resistance. In addition, knockout of the gene PCDH10L indicates that PCDH10L affects Pb 2+ -induced mortality in rare minnow. Rare minnow is ready for genetic manipulation and shows potential as an emerging experimental model.

Background The black widow spider has both extraordinarily neurotoxic venom and three-dimensional cobwebs composed of diverse types of silk. However, a high-quality reference genome for the black widow spider was still unavailable, which hindered deep understanding and application of the valuable biomass. Findings We assembled the Latrodectus elegans genome, including a genome size of 1.57 Gb with contig N50 of 4.34 Mb and scaffold N50 of 114.31 Mb. Hi-C scaffolding assigned 98.08% of the genome to 14 pseudo-chromosomes, and with BUSCO, completeness analysis revealed that 98.4% of the core eukaryotic genes were completely present in this genome. Annotation of this genome identified that repetitive sequences account for 506.09 Mb (32.30%) and 20,167 protein-coding genes, and specifically, we identified 55 toxin genes and 26 spidroins and provide preliminary analysis of their composition and evolution. Conclusions We present the first chromosome-level genome assembly of a black widow spider and provide substantial toxin and spidroin gene resources. These high-qualified genomic data add valuable resources from a representative spider group and contribute to deep exploration of spider genome evolution, especially in terms of the important issues on the diversification of venom and web-weaving pattern. The sequence data are also firsthand templates for further application of the spider biomass.

Origination of new genes are of inherent interest of evolutionary geneticists for decades, but few studies have addressed the general pattern in a fish lineage. Using our recent released whole genome data of flatfishes, which evolved one of the most specialized body plans in vertebrates, we identified 1541 (6.9% of the starry flounder genes) flatfish-lineage-specific genes. The origination pattern of these flatfish new genes is largely similar to those observed in other vertebrates, as shown by the proportion of DNA-mediated duplication (1317, 85.5%), RNA-mediated duplication (retrogenes, 96, 6.2%), and de novo&amp, x2013, origination (128, 8.3%). The emergence rate of species-specific genes is 32.1 per Mya and the whole average level rate for the flatfish-lineage-specific genes is 20.9 per Mya. A large proportion (31.4%) of these new genes have been subjected to selection, in contrast to the 4.0% in primates, while the old genes remain quite similar (66.4% vs. 65.0%). In addition, most of these new genes (70.8%) are found to be expressed, indicating their functionality. This study not only presents one example of systematic new gene identification in a teleost taxon based on comprehensive phylogenomic data, but also shows that new genes may play roles in body planning.

Ruminants comprise a highly successful group of mammals with striking morphological innovations, including the presence of a rumen. Many studies have shown that species-specific or lineage-specific genes (referred to as new genes) play important roles in phenotypic evolution. In this study, we identified 1064 ruminant-specific genes based on the newly assembled high-quality genomes of representative members of two ruminant families and other publically available high-quality genomes. Ruminant-specific genes shared similar evolutionary and expression patterns with new genes found in other mammals, such as primates and rodents. Most new genes were derived from gene duplication and tended to be expressed in the testes or immune-related tissues, but were depleted in the adult brain. We also found that most genes expressed in the rumen were genes predating sheep-sperm whale split (referred to as old genes), but some new genes were also involved in the evolution of the rumen, and contributed more during rumen development than in the adult rumen. Notably, expression levels of members of the ruminant-specific PRD-SPRRII gene family, which are subject to positive selection, varied throughout rumen development and may thus play important roles in the development of the keratin-rich surface of the rumen. Overall, this study generated two novel ruminant genomes and also provided novel insights into the evolution of new mammalian organs.

Horseshoe crabs including Tachypleus tridentatus are a group of marine arthropods and living fossil species which have existed on the earth for ~500 million years. However, the genetic mechanisms underlying their unique adaptive ability are still unclear. Here, we assembled the first chromosome-level T. tridentatus genome, and proved that this genome is of high quality with contig N50 1.69 Mb. By comparison with other arthropods, some gene families of T. tridentatus experienced significant expansion, which are related to several signaling pathways, endonuclease activities, and metabolic processes. Based on the results of comparative analysis of genomics and 27 transcriptomes from nine tissues, we found that the expanded Dscam genes are located at key hub positions of immune network. Furthermore, the Dscam genes showed higher levels of expression in the yellow connective tissue (the birthplace of blood cells with strong differentiation capability) than the other eight tissues. Besides, the Dscam genes are positively correlated with the expression of the core immunity gene, clotting factor B, which is involved in the coagulation cascade reaction. The effective and unusual immune ability endowed by the expansion and expression of Dscam genes in the horseshoe crab may be a factor that makes the species have a strong environmental adaptability within ~500 million years. The high quality chromosome level genome of a horseshoe crab and unique genomic features reported in this study provide important data resources for future studies on the evolution of marine ecological systems.

Protein therapeutics are increasingly used to treat various diseases, yet they often suffer from short serum half-lives. An emerging strategy to extend lifetime in vivo is to attach fatty acids onto proteins to increase their binding to human serum albumin (HSA). Herein, the genetic encoding of ϵ-N-heptanoyl-l-lysine (HepoK) is reported, which introduces a fatty-acid-containing amino acid into proteins with exquisite site-specificity and homogeneity, overcoming issues associated with existing chemical conjugation methods. The expression in E .coli and purification of HepoK-incorporated glucagon-like peptide-1 (GLP1) is demonstrated. GLP1(HepoK) showed stronger binding to HSA than GLP1(WT), without impairing the stimulation of the GLP1 receptor in cells. Moreover, GLP1(HepoK) decreased blood glucose level to the same level as GLP1(WT) in mice, showing longer-lasting effects than GLP1(WT). HepoK incorporation will also be useful for investigating the function of protein lipidation.

This study aimed to develop and incorporate a secondary electrospray ionization (SESI) setup in combination with both targeted tandem mass spectrometry (MS/MS) and a hybrid metabolomics technique, globally optimized targeted mass spectrometry (GOT-MS), to sensitively detect volatile metabolites from the headspace of in vitro gut microbial culture in a human colonic model (HCM). Two SESI-tandem mass spectrometry panels with a comparable number of targeted metabolites/features (77 compounds in the targeted SESI-MS/MS panel and 75 features in the SESI-GOT-MS/MS panel) were established. The analytical performance of the SESI-GOT-MS/MS method, as well as its biological capability, were examined and compared with the targeted SESI-MS/MS method. As a result, the SESI-GOT-MS/MS method detected a similar number of metabolic features with good reproducibility (coefficient of variation

Mitochondria are dynamic multitask organelles that function as hubs for many metabolic pathways. They produce most ATP via the oxidative phosphorylation pathway, a critical pathway that the brain relies on its energy need associated with its numerous functions, such as synaptic homeostasis and plasticity. Therefore, mitochondrial dysfunction is a prevalent pathological hallmark of many neurodevelopmental and neurodegenerative disorders resulting in altered neurometabolic coupling. With the advent of mass spectrometry (MS) technology, MS-based metabolomics provides an emerging mechanistic understanding of their global and dynamic metabolic signatures. In this review, we discuss the pathogenetic causes of mitochondrial metabolic disorders and the recent MS-based metabolomic advances on their metabolomic remodeling. We conclude by exploring the MS-based metabolomic functional insights into their biosignatures to improve diagnostic platforms, stratify patients, and design novel targeted therapeutic strategies.

Purpose Widespread use of sensitive ultrasound examination led to an increasing detection of medullary thyroid microcarcinoma (micro-MTC). This prospective study evaluated the diagnostic accuracy of Fine-needle Aspiration Biopsy Cytology (FNAB-C) and calcitonin assay in Fine-needle Aspiration Biopsy wash-out fluid (FNAB-CT) in thyroid nodules less than 1cm with elevated serum calcitonin. Methods 87 thyroid nodules from 60 patients with elevated serum calcitonin(＞10pg/ml) were included and 51 were thyroid nodules less than 1cm. FNAB-CT and FNAB-C was performed to distinguish MTC lesions before surgery, histopathologic diagnoses served as main reference standards.Results FNAB-CT had a greater performance over FNAB-C for preoperative diagnosis of MTC (diagnostic accuracy: 98.85％vs 61.90％, sensitivity: 98.55％ vs 55.07％, specificity: 100％ vs 97.44％), especially for micro-MTC: FNAB-C established a sensitivity and diagnostic accuracy of 48.78％ and 58％ respectively, while FNAB-CT reached 97.56% sensitivity and 98.04% diagnostic accuracy. Conclusions FNAB-CT demonstrated high diagnostic accuracy in diagnosing micro-MTC. Patients with micro thyroid nodules and elevated sCT level should perform FNAB-CT to exclude the diagnosis of MTC lesions.

Context Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive genetic diseases caused by genetic deficiency in nine genes encoding steroidogenesis enzymes and cofactors. Objective To establish a targeted next-generation sequencing (NGS) assay for all nine CAH candidate genes. Methods We developed a customized targeted NGS assay of CAH candidate genes (CYP21A2, CYP17A1, CYP11B1, StAR, CYP11A1, POR, HSD3B2, H6PD, CYP11B2) and apply this assay plus MLPA of CYP21A2 in a total of 469 patients with CAH like signs and symptoms. Results We totally identified 125 variants with seven variant types in eight genes. Variant types included missense variant (46.8 %), splicing variant (21.5 %), small indel (12.5 %), large structure variation (11.8 %), nonsense variant (4.1 %), UTR variant (2.9 %), synonymous variant (0.3 %). Successful genotyping, defined as biallelic pathogenic or likely pathogenic variants, was achieved in 98.5 % (336/341) of cases, including biallelic variants in CYP21A2 (n = 254), CYP17A1 (n = 45), CYP11B1 (n = 23), StAR (n = 7), HSD3B2 (n = 4), POR (n = 1), CYP11A1 (n = 1) and CYP11B2 (n = 1) gene. Importantly, the assay found one patient with CYP11B1 deficiency, one patient with non-classic POR deficiency and two patients with non-classic CYP17A1 deficiency while clinically diagnosed differently. Conclusions Our NGS-based assay plus MLPA of CYP21A2 is a useful tool to genotype all subtypes of CAH. The test successfully achieved genotype in 98.5 % of patients with clinically determined CAH. It also efficiently facilitated the diagnosis of CAH in patients with rare subtypes as well as non-classic phenotypes.

The evolutionary and genetic origins of the specialized body plan of flatfish are largely unclear. We analyzed the genomes of 11 flatfish species representing 9 of the 14 Pleuronectiforme families and conclude that Pleuronectoidei and Psettodoidei do not form a monophyletic group, suggesting independent origins from different percoid ancestors. Genomic and transcriptomic data indicate that genes related to WNT and retinoic acid pathways, hampered musculature and reduced lipids might have functioned in the evolution of the specialized body plan of Pleuronectoidei. Evolution of Psettodoidei involved similar but not identical genes. Our work provides valuable resources and insights for understanding the genetic origins of the unusual body plan of flatfishes., Analysis of 11 flatfish genomes indicates that Pleuronectoidei and Psettodoidei are not a monophyletic group. Genomic and transcriptomic data suggest that the WNT and RA pathways played a role in the evolution of the specialized body of flatfish.

Background The swimming crab, Portunus trituberculatus, is an important commercial species in China and is widely distributed in the coastal waters of Asia-Pacific countries. Despite increasing interest in swimming crab research, a high-quality chromosome-level genome is still lacking. Findings Here, we assembled the first chromosome-level reference genome of P. trituberculatus by combining the short reads, Nanopore long reads, and Hi-C data. The genome assembly size was 1.00 Gb with a contig N50 length of 4.12 Mb. In addition, BUSCO assessment indicated that 94.7% of core eukaryotic genes were present in the genome assembly. Approximately 54.52% of the genome was identified as repetitive sequences, with a total of 16,796 annotated protein-coding genes. In addition, we anchored contigs into chromosomes and identified 50 chromosomes with an N50 length of 21.80 Mb by Hi-C technology. Conclusions We anticipate that this chromosome-level assembly of the P. trituberculatus genome will not only promote study of basic development and evolution but also provide important resources for swimming crab reproduction.

Data-driven technologies for intelligent building energy management and automation have been developed under the energy balance state of systems. The datasets required are typically derived using energy and mass balance principles at each system boundary. Hence, the energy balance of systems significantly affects the system and building performances. However, sensor errors in a building energy sensor network can hinder the identification of balance states, thereby causing energy balance calculation errors in operational systems. In this study, the cooling capacity balance errors between the air and refrigerant sides of two unitary air-conditioner systems, caused by measurement errors, are investigated experimentally. Virtual in-situ sensor calibration (VIC) is performed to determine hidden sensor errors that cause the cooling capacity balance error, as well as to improve the balance and the degraded system performance analysis by calibrating the measurement errors. Experiments reveal the extent of cooling capacity balance errors occurring between the air and refrigerant sides under different operational conditions (0.5%–14.8%). VIC reveals erroneous measurements and the manner by which energy balance errors with measurement errors are solved (below 2%). Finally, the system performance analysis of the two test units shows that the VIC-driven calibration datasets improve the accuracy (0.3%–1.8% errors) of the system energy efficiency ratio even for new test cases after VIC is applied. The primary contributions of this study are as follows: (1) VIC is applied to solve energy balance calculation errors; (2) a strategy is proposed to overcome insufficient datasets to ensure energy balance improvements; and (3) calibrated measurements in real systems are validated.

An intelligent fault diagnosis network for variable refrigerant flow air conditioning system is proposed in this study. The network is developed under the foundation of bayesian belief network theory, which comprises two main elements: the structure and parameters. The structure obtained by machine learning and experts’ experiences illustrates the relationships among faults and physical variables from the qualitative prospective, and its parameters (including prior probability distribution and conditional distribution) describe the uncertainty between them quantitatively. Once the structure and parameters are determined, the posterior probability distribution which can be used to complete fault diagnosis and isolation will be calculated by some algorithms. In comparison with other fault diagnosis approaches, the proposed approach can make full use of performance information. Moreover, it is more reasonable and precise to express the relationship between faults and variables rather than Boolean variables. Evaluation was conducted on a variable refrigerant flow air conditioning system, which demonstrated that this strategy is effective and efficient.

This paper proposes an improved decision tree (DT)-based fault diagnosis method for practical variable refrigerant flow (VRF) system. The proposed method is a three-stage method combining DT model with virtual sensor-based fault indicators (FIs). First, FIs are developed based on the virtual sensor (VS) theory for VRF faults, i.e., condenser air-side fouling (Fouling), refrigerant undercharge (RU) and overcharge (RO). Second, FIs are employed as additional input variables to induct a DT-based classification model classification and regression tree (CART). Third, the FIs-CART classification model is used to diagnose on-line data. Validation is conducted using two different datasets, the experimental testing dataset and the on-line testing dataset. Results indicate that the method correctly isolates the three faults i.e., Fouling, RU and RO. The improved DT method is also compared with three tree-based data-driven methods including CART, random forest (RF) and generalized boosted regression (GBM). Comparative results reveal that the proposed method has better fault diagnosis performance for both the experimental and the on-line testing datasets.

Rationale Pathogenic foodborne bacteria have been associated with severe infectious disease in humans and animals worldwide. Rapid detection and screening of these foodborne pathogens are critical for our food safety. This study aimed at detecting Escherichia coli and Staphylococcus aureus, two important foodborne bacteria, at the species and strain/serovar level using a mass spectrometry (MS)-based targeted metabolic profiling approach. Methods Ten E. coli strains (8 out of 10 were foodborne outbreak isolates) and four S. aureus strains were tested at two growth time points. A high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS)-based targeted metabolomics approach was applied for metabolic profile based bacteria detection. A total of 108 metabolites from multiple metabolic pathways were confidently detected from these bacteria. Results Our study demonstrated that with only 4 h of enrichment in the same medium, the metabolic profiles from E. coli and S. aureus showed significant difference. Furthermore, seven out of ten E. coli strains and all four tested S. aureus strains showed strain/serovar-level differentiation at the 4-h time point, which indicated great potential for strain level stratification in future food screening using our MS-based targeted metabolic profiling approach. Conclusions A targeted metabolomics method was developed to demonstrate the utility of HPLC/MS/MS-based metabolic profiling in rapidly (4 h) differentiating E. coli and S. aureus bacteria, two of the most notorious foodborne bacteria, at both the species and strain/serovar levels. The results indicated that our approach has great potential in the future for fast and specific detection of foodborne pathogenic bacteria based on their metabolic diversity.

A multi-functional heat pump system has been proposed to effectively utilize waste heat and heat capacity in gray water for heating and cooling of residential buildings. Condenser heat recovery is integrated into the system. This system was tested in two environmental chambers that mimic the outdoor and indoor environments, respectively. In this paper, the investigation of the optimized system is focused on the system optimization and performance in cooling mode. The drawbacks of the initial prototype are analyzed and fixed. The system performance in the initial and optimized prototypes are compared and analyzed. At outdoor temperature 35 °C, compared to initial type, the COP of optimized prototype increases up to 20.07% for space cooling mode and up to 21.51% for space cooling with hot water supply mode. This system is tested and analyzed at space cooling mode, space cooling with hot water supply mode and hot water supply only mode.

Sensor faults of air conditioning systems are harmful to optimal control strategies and system performance resulting in poor control of the indoor environment and waste of energy. In order to improve the fault detection and diagnosis (FDD) performance, this paper presents an enhanced sensor fault detection and diagnosis method based on the Satizky-Golay (SG) method and principal component analysis (PCA) method for the VRF system, namely SG-PCA method. Due to the volatility of the original data set of VRF system, the original data are smoothed using SG method at first. Then, the smoothed data are used for PCA model training and fault detection and diagnosis. In order to determine parameters of the SG method, an optimization index is proposed, which is calculated by the signal to noise ratio (SNR), the standard deviation (SD) and the self-detection efficiency. This SG-PCA method for VRF system sensor FDD is validated using field operation data of the VRF system. Various sensor faults at different fault levels are introduced. The results have showed that the SG-PCA method can significantly improve the fault detection and diagnosis performance compared to conventional PCA method.

Developing fault detection and diagnosis (FDD) for the variable refrigerant flow (VRF) system is very important for saving energy and improving reliability of the equipment. For indoor unit (IDU) faults of VRF system, it is especially necessary to detect faults and identify which IDU is faulty. Therefore, this paper has proposed a fault detection strategy based on modularized PCA method, which cannot only detect faults but also specify the faulty IDU. Fault detection models are established respectively for outdoor unit (ODU) and IDUs of VRF system using the modularized PCA method. Then, the expert-based multivariate decoupling strategy with six variables for VRF system is developed to isolate faults. Four common faults are taken into account for VRF system, which include two IDUs faults (electronic expansion valve fault and IDU air-side fouling), one ODU fault (reversing valve stick) and one system fault (refrigerant undercharge). The proposed FDD strategy is evaluated by experimental data of four faults. The test results have shown that modularized PCA-based fault detection method and rule-based diagnosis method are effective for the four typical faults in VRF system. Therefore, it is quite suitable for FDD of VRF system.