High Molecular Weight Semicrystalline Substituted Polycyclohexene From Alternating Copolymerization of Butadiene and Methacrylate and Its Ambient Depolymerization.

Cyclohexene cannot be polymerized via ring-opening polymerization under any conditions due to its lack of ring strain. A hypothetical polycyclohexene would therefore have a strong thermodynamic driving force to depolymerize to monomer if a metathesis catalyst were provided while otherwise having thermal and hydrolytic stability under normal conditions because of its hydrocarbon backbone. We envisioned access to this otherwise unattainable family of polymers via the alternating polymerization of a diene and an alkene. Ethyl aluminum chloride was found to promote highly alternating polymerization of butadiene and methacrylate when radically initiated at room temperature, resulting in formal polycyclohexene structures. Ultrahigh molecular weight (up to 1750 kDa) polymers can be synthesized at the decagram scale in high monomer conversions. The resulting presumably atactic copolymers exhibited semicrystallinity, leading to high toughness. In the presence of a small amount of the Grubbs catalyst, the generated polycyclohexene can be fully depolymerized at ambient temperatures into pure constituent cyclohexene. The strategy of using orthogonal chemistry for the polymerization and depolymerization processes allows access to polymer structures with subambient ceiling temperatures without using ultralow temperature synthesis or relying on the monomer-polymer equilibrium.

Mechanochemistry of Pterodactylane.

Pterodactylane is a [4]-ladderane with substituents on the central rung. Comparing the mechanochemistry of the [4]-ladderane structure when pulled from the central rung versus the end rung revealed a striking difference in the threshold force of mechanoactivation: the threshold force is dramatically lowered from 1.9 nN when pulled on the end rung to 0.7 nN when pulled on the central rung. We investigated the bicyclic products formed from the mechanochemical activation of pterodactylane experimentally and computationally, which are distinct from the mechanochemical products of ladderanes being activated from the end rung. We compared the products of pterodactylane's mechanochemical and thermal activation to reveal differences and similarities in the mechanochemical and thermal pathways of pterodactylane transformation. Interestingly, we also discovered the presence of elementary steps that are accelerated or suppressed by force within the same mechanochemical reaction of pterodactylane, suggesting rich mechanochemical manifolds of multicyclic structures. We rationalized the greatly enhanced mechanochemical reactivity of the central rung of pterodactylane and discovered force-free ground state bond length to be a good low-cost predictor of the threshold force for cyclobutane-based mechanophores. These findings advance our understanding of mechanochemical reactivities and pathways, and they will guide future designs of mechanophores with low threshold forces to facilitate their applications in force-responsive materials.

Inhibition of transglutaminase 2 inhibits ionizing radiation-induced cellular senescence in skin keratinocytes in vitro.

Senescent cells are typically characterized by a stable proliferation arrested in dividing cells accompanied with a senescence-associated secretory phenotype (SASP). Skin cellular senescence is the primary cause of skin aging, whereas the lack of identified skin senescence markers limits our understanding of the mechanisms involved in skin aging. Recent studies have revealed that intracellular calcium signaling has emerged as a key player in regulating cellular senescence and aging. However, the implication and roles of calcium signaling in skin keratinocyte senescence remain only partially understood. In this study, we developed a model for skin keratinocyte senescence using ionizing radiation (I/R) stimulation and found that the calcium-associated gene transglutaminase 2 (TGM2) was significantly induced compared with normal control. Interestingly, inhibition of TGM2 was found to delay skin keratinocyte senescence by suppressing I/R-promoted intracellular calcium signaling, accumulation of reactive oxygen species (ROS), DNA damage, as well as NF-κB-mediated SASP secretion. Taken together, our findings demonstrate that inhibition of TGM2 contributes to bypassing I/R-induced skin keratinocyte senescence and sheds light on novel strategies against skin stresses caused by I/R.

Detection and complete genome sequence analysis of human adenovirus in children with acute diarrhea in Yunnan, China, 2015-2021.

The aims of this study were to determine the distribution and prevalence of gastroenteritis caused by human adenovirus (HAdV) in children in Yunnan province, China, in 2015-2021 and to identify preventive measures that can be taken to reduce morbidity and mortality in children.HAdV is a significant agent of diarrhea in children, but limited data are available regarding the epidemiology and genetic diversity of HAdV in children with diarrhea in Yunnan province, China. A total of 1754 fecal samples were subjected to real-time RT-PCR to detect and quantify HAdV. Positive samples were further analyzed using next-generation sequencing (NGS), and epidemiological data were analyzed as well.1754 patients with diarrhea were enrolled, of which 1041 were male and 713 were female (M:F ratio: 1.46). Seventy-two stool samples out of 1754 (4.10%) were positive for HAdV. The detection rates of all age groups varied from 2.50-4.78%. The highest incidence of HAdV was observed in children under 2 years of age, especially in children 12-24 months-old. From 2015-2021, the annual detection rate ranged from 1.62-12.26%. HAdV was detected throughout the year, but with marked seasonality. Children were most likely to be positive for HAdV in June and November. We detected HAdV in 15.53% (16/103) of samples collected in June and in 8.19% (14/171) of those collected in November. The entire viral genome was successfully sequenced for 13 of the 72 HAdV-positive samples, and 76.92% (10/13) of these were classified as genotype F41 and 23.08% (3/13) were classified as genotype C2.ConclusionsIn Yunnan province, children of all ages are susceptible to HAdV infection, but there has been marked variation in the yearly prevalence. The highest rate of HAdV detection was in June, followed by November. Priority should be given to disease prevention over the development of targeted antiviral therapies, and effective vaccines for preventing HAdV diarrhea are needed. It is also important to establish a surveillance system to collect relevant clinical and epidemiological data quickly in order to assess the potential risk of HAdV infection in children and to identify epidemic strains for the development of effective vaccines.

Image fusion-based low-dose CBCT enhancement method for visualizing miniscrew insertion in the infrazygomatic crest.

Digital dental technology covers oral cone-beam computed tomography (CBCT) image processing and low-dose CBCT dental applications. A low-dose CBCT image enhancement method based on image fusion is proposed to address the need for subzygomatic small screw insertion. Specifically, firstly, a sharpening correction module is proposed, where the CBCT image is sharpened to compensate for the loss of details in the underexposed/over-exposed region. Secondly, a visibility restoration module based on type II fuzzy sets is designed, and a contrast enhancement module using curve transformation is designed. In addition to this, we propose a perceptual fusion module that fuses visibility and contrast of oral CBCT images. As a result, the problems of overexposure/underexposure, low visibility, and low contrast that occur in oral CBCT images can be effectively addressed with consistent interpretability. The proposed algorithm was analyzed in comparison experiments with a variety of algorithms, as well as ablation experiments. After analysis, compared with advanced enhancement algorithms, this algorithm achieved excellent results in low-dose CBCT enhancement and effective observation of subzygomatic small screw implantation. Compared with the best performing method, the evaluation metric is 0.07-2 higher on both datasets. The project can be found at: https://github.com/sunpeipei2024/low-dose-CBCT .

Hypoalgesia and Conditioned Pain Modulation in Blood Flow Restriction Resistance Exercise.

We compared the magnitude of exercise-induced hypoalgesia and conditioned pain modulation between blood-flow restriction (BFR) resistance exercise (RE) and moderate-intensity RE. Twenty-five asymptomatic participants performed unilateral leg press in two visits. For moderate-intensity RE, subjects exercised at 50% 1RM without BFR, whereas BFR RE exercised at 30% 1RM with a cuff inflated to 60% limb occlusion pressure. Exercise-induced hypoalgesia was quantified by pressure pain threshold changes before and after RE. Conditioned pain modulation was tested using cold water as the conditioning stimulus and mechanical pressure as the test stimulus and quantified as pressure pain threshold change. Difference in conditioned pain modulation pre- to post-RE was then calculated. The differences of RE on pain modulations were compared using paired t-tests. Pearson's r was used to examine the correlation between exercise-induced hypoalgesia and changes in conditioned pain modulation. We found greater hypoalgesia with BFR RE compared to moderate-intensity RE (p=0.008). Significant moderate correlations were found between exercise-induced hypoalgesia and changes in conditioned pain modulation (BFR: r=0.63, moderate-intensity: r=0.72). BFR RE has favorable effects on pain modulation in healthy adults and the magnitude of exercise-induced hypoalgesia is positively correlated with conditioned pain modulation activation.

Abietane-Type Diterpenoids from the Arils of Torreya grandis.

A chemical investigation of the arils of Torreya grandis led to the isolation of seven abietane-type diterpenoids (compounds 1-7) including three previously undescribed compounds, one unreported natural product, and three known analogs. The structures of these compounds were determined by means of spectroscopy, single-crystal X-ray diffraction, and ECD spectra. An antibacterial activity assay showed that compounds 5 and 6 had significant inhibitory effects on methicillin-resistant Staphylococcus aureus, with MIC values of 100 µM. Moreover, compounds 1, 3, 4, and 7 exhibited anti-neuroinflammatory activity in LPS-stimulated BV-2 microglia cells, with the IC50 values ranging from 38.4 to 67.9 µM.

Increased Risk of Neurological Disease Following Pediatric Rotavirus Infection: A Two-Center Case-Control Study.

BACKGROUND: Whether pediatric rotavirus infection is associated with extraintestinal complications remains unknown. METHODS: We conducted a case-control study to investigate the incidences and risks of rotavirus-associated extraintestinal complications in hospitalized newborns, infants, and children younger than 5 years. RESULTS: A total of 1325 young inpatients with rotavirus infection (754 male and 539 newborns) and 1840 controls without rotavirus infection (1035 male and 836 newborns) were included. The incidences of neurological disease were higher among rotavirus individuals compared with controls: newborns, 7.24% (39/539) versus 2.87% (24/836), P < .001; infants and young children, 19.59% (154/786) versus 12.35% (124/1004), P < .001. The associated odd ratios (ORs) for neurological disease frequency following rotavirus infection was 2.64 (95% confidence interval [CI], 1.57-4.44) for newborns and 1.73 (95% CI, 1.34-2.24) for infants and young children, which increased to 2.56 (95% CI, 1.57-4.18) in case-control (1:1) matching analysis and 1.85 (95% CI, 1.41-2.42) in confounder adjustment. Rotavirus infection was associated with other extraintestinal complications, depending on study population and disease severity. Outcome analysis revealed rotavirus infection and its consequences had a significant impact on hospitalization and discharge. CONCLUSIONS: Rotavirus exposure was associated with a spectrum of extraintestinal complications, particularly neurological disease. Rotavirus infection and subsequent consequences resulted in poor clinical outcomes.

Force Transduction Through Distant Force-Bearing Regioisomeric Linkages Affects the Mechanochemical Reactivity of Cyclobutane.

Fundamental understanding of mechanochemical reactivity is important for designing new mechanophores. Besides the core structure of mechanophores, substituents on a mechanophore can affect its mechanochemical reactivity through electronic stabilization of the intermediate or effectiveness of force transduction from the polymer backbone to the mechanophore. The latter factor represents a unique mechanical effect in considering polymer mechanochemistry. Here, we show that regioisomeric linkage that is not directly adjacent to the first cleaving bond in cyclobutane can still significantly affect the mechanochemical reactivity of the mechanophore. We synthesized three non-scissile 1,2-diphenyl cyclobutanes, varying their linkage to the polymer backbone via the o, m, or p-position of the diphenyl substituents. Even though the regioisomers share the same substituted cyclobutane core structure and similar electronic stabilization of the diradical intermediate from cleaving the first C-C bond, the p isomer exhibited significantly higher mechanochemical reactivity than the o and m isomers. The observed difference in reactivity can be rationalized as the much more effective force transduction to the scissile bond through the p-position than the other two substitution positions. These findings point to the importance of considering force-bearing linkages that are more distant from the bond to be cleaved when incorporating mechanophores into polymer backbones.

Mutualistic Synthesis from Orthogonal Dynamic Covalent Reactions.

Mutualisms are interactions that benefit all species involved. It has been widely investigated in neighbouring subjects, such as biology, ecology, sociology, and economics. However, such a reciprocal relationship in synthetic chemical systems has rarely been studied. Here, we demonstrate a mutualistic synthesis where byproducts from two orthogonal chemical reactions aid each other's production. Disulfide exchange and hydrazone exchange were chosen to generate two dynamic combinatorial libraries. A minor tetrameric macrocycle from the active disulfide library was quantitatively amplified in the presence of the hydrazone library. This incorporation also turned on the previously inert hydrazone reaction, producing a linear species that formed a "handcuffs" catenane with the disulfide tetramer. These findings not only lend robust support to the hypothesis of "RNA-peptide coevolution" for the origin of life but also broaden the scope of synthetic chemistry, highlighting the untapped potential of minor products from different reactions. Additionally, the co-self-assembly of these mutualistic entities to form supramolecular structures opens new avenues for future development of composite nanosystems with synergistic properties.

[Autosomal recessive polycystic kidney disease in a girl]. / å¸¸æŸ“è‰²ä½“éšæ€§é—ä¼ æ€§å¤šå›Šè‚¾1例.

A 5-year-old girl was admitted due to one episode of melena and one episode of hematemesis. Upon admission, gastroscopy revealed esophageal and gastric varices. Abdominal CT scan, MRI, and color Doppler ultrasound suggested cirrhosis, intrahepatic bile duct dilation, and bilateral kidney enlargement. Genetic testing identified compound heterozygous mutations in the PKHD1 gene: c.2264C>T (p.Pro755Leu) and c.1886T>C (p.Val629Ala). The c.2264C>T (p.Pro755Leu) mutation is a known pathogenic variant with previous reports, while c.1886T>C (p.Val629Ala) is a novel mutation predicted to have pathogenic potential according to Mutation Taster and PolyPhen2. The child was diagnosed with autosomal recessive polycystic kidney disease. In children presenting with gastrointestinal bleeding without obvious causes, particularly those with liver or kidney disease, consideration should be given to the possibility of autosomal recessive polycystic kidney disease, and genetic testing should be conducted for definitive diagnosis when necessary.

Monolithically integrated 112 Gbps PAM4 optical transmitter and receiver in a 45†nm CMOS-silicon photonics process.

We demonstrate a transmitter and receiver in a silicon photonics platform for O-band optical communication that monolithically incorporates a modulator driver, traveling-wave Mach-Zehnder modulator, control circuitry, photodetector, and transimpedance amplifier (TIA) in the GlobalFoundries Fotonix (45SPCLO) platform. The transmitter and receiver show an open 112 Gbps PAM4 eye at a 4.3 pJ/bit energy efficiency, not including the laser. Extensive use of gain-peaking enables our modulator driver and TIA to achieve the high bandwidths needed in the 45 nm CMOS-silicon photonics process. Our results suggest an alternative to the frequent approach of bump-bonding BiCMOS drivers and TIAs to silicon photonics.

HMGB1 is involved in viral replication and the inflammatory response in coxsackievirus A16-infected 16HBE cells via proteomic analysis and identification.

Coxsackievirus A16 (CV-A16) is still an important pathogen that causes hand, foot and mouth disease (HFMD) in young children and infants worldwide. Previous studies indicated that CV-A16 infection is usually mild or self-limiting, but it was also found that CV-A16 infection can trigger severe neurological complications and even death. However, there are currently no vaccines or antiviral compounds available to either prevent or treat CV-A16 infection. Therefore, investigation of the virus‒host interaction and identification of host proteins that play a crucial regulatory role in the pathogenesis of CV-A16 infection may provide a novel strategy to develop antiviral drugs. Here, to increase our understanding of the interaction of CV-A16 with the host cell, we analyzed changes in the proteome of 16HBE cells in response to CV-A16 using tandem mass tag (TMT) in combination with LC‒MS/MS. There were 6615 proteins quantified, and 172 proteins showed a significant alteration during CV-A16 infection. These differentially regulated proteins were involved in fundamental biological processes and signaling pathways, including metabolic processes, cytokine‒cytokine receptor interactions, B-cell receptor signaling pathways, and neuroactive ligand‒receptor interactions. Further bioinformatics analysis revealed the characteristics of the protein domains and subcellular localization of these differentially expressed proteins. Then, to validate the proteomics data, 3 randomly selected proteins exhibited consistent changes in protein expression with the TMT results using Western blotting and immunofluorescence methods. Finally, among these differentially regulated proteins, we primarily focused on HMGB1 based on its potential effects on viral replication and virus infection-induced inflammatory responses. It was demonstrated that overexpression of HMGB1 could decrease viral replication and upregulate the release of inflammatory cytokines, but deletion of HMGB1 increased viral replication and downregulated the release of inflammatory cytokines. In conclusion, the results from this study have helped further elucidate the potential molecular pathogenesis of CV-A16 based on numerous protein changes and the functions of HMGB1 Found to be involved in the processes of viral replication and inflammatory response, which may facilitate the development of new antiviral therapies as well as innovative diagnostic methods.

POU Domain Class 2 Transcription Factor 2 Inhibits Ferroptosis in Cerebral Ischemia Reperfusion Injury by Activating Sestrin2.

Cerebral ischemia reperfusion injury (CIRI) is the commonest cause of brain dysfunction. Up-regulation of POU domain class 2 transcription factor 2 (POU2F2) has been reported in patients with cerebral ischemia, while the role of POU2F2 in CIRI remains elusive. Middle cerebral artery occlusion/reperfusion (MCAO/R) in mice and oxygen and glucose deprivation/reperfusion (OGD/R) in mouse primary cortical neurons were used as models of CIRI injury in vivo and in vitro. Lentivirus-mediated POU2F2 knockdown further impaired CIRI induced by MCAO/R in mice, which was accompanied by increased-neurological deficits, cerebral infarct volume and neuronal loss. Our evidence suggested that POU2F2 deficiency deteriorated oxidative stress and ferroptosis according to the phenomenon such as the abatement of SOD, GSH, glutathione peroxidase 4 (GPX4) activity and accumulation of ROS, lipid ROS, 4-hydroxynonenal (4-HNE) and MDA. In vivo, primary cortical neurons with POU2F2 knockdown also showed worse neuronal damage, oxidative stress and ferroptosis. Sestrin2 (Sesn2) was reported as a neuroprotection gene and involved in ferroptosis mechanism. Up-regulation of Sesn2 was observed in the ischemic penumbra and OGD/R-induced neuronal cells. Further, we proved that POU2F2, as a transcription factor, could bind to Sesn2 promoter and positively regulate its expression. Sesn2 overexpression relieved oxidative stress and ferroptosis induced by POU2F2 knockdown in OGD/R-treated neurons. This research demonstrated that CIRI induced a compensatory increase of POU2F2 and Sesn2. Down-regulated POU2F2 exacerbated CIRI through the acceleration of oxidative stress and ferroptosis possibly by decreasing Sesn2 expression, which offers new sights into therapeutic mechanisms for CIRI.

Erythropoietin inhibits neutrophil extracellular traps formation to ameliorate lung injury in a pneumonia model.

BACKGROUND: Severe pneumonia is a kind of disease that develops from lung inflammation, and new drugs are still required to treat the same. Erythropoietin (EPO) is widely used to treat anemia in patients. However, there are fewer studies on the role of EPO in neutrophil extracellular trappings (NETs) and pneumonia, and the mechanism is unclear. OBJECTIVE: To investigate the possible effects of EPO on the formation of NETs and progression of pneumonia. METHODS: Mice pneumonia model was induced by tracheal lipopolysaccharide (LPS) administration. Hematoxylin and eosin (H&E) staining and automatic blood cell analysis were performed in this model to confirm the effects of EPO on lung injury. Flow cytometry, enzyme-linked immunosorbent serological assay, and immunostaining assay were conducted to detect the effects of EPO on the inflammation as well as formation of NETs in mice. Immunoblot was further conducted to confirm the mechanism. RESULTS: EPO alleviated LPS-induced lung injury. EPO reduced the release of inflammatory factors induced by LPS. In addition, EPO inhibited the formation of NETs. Mechanically, EPO inhibited tumor necrosis factor (TNF) receptor associated factor 2 (TRAF2)/nuclear factor kappa-B (NF-κB) activity in mouse models, and therefore suppressed the progression of pneumonia. CONCLUSION: EPO inhibited formation of NETs to ameliorate lung injury in a pneumonia model, and could serve as a drug of pneumonia.

STAM binding protein regulated by hsa_circ_0007334 exerts oncogenic potential in pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) is a highly aggressive and metastatic malignancy. The molecular events related to PC have not yet been fully elucidated. The STAM binding protein (STAMBP), a deubiquitinase, contributes to carcinogenesis in several types of cancer. Our study aims to investigate the function of STAMBP in the progression of PC. METHODS: Fifteen pairs of tumor and tumor-adjacent tissues were obtained from PC patients. Human pancreatic cancer cell lines, SW 1990 and BxPC-3, were transfected with short hairpin RNA targeting STAMBP or/and vectors overexpressing wild-type STAMBP or STAMBP D348A mutants (inactive mutants of STAMBP). SW 1990 cells were co-transfected with vectors overexpressing STAMBP and small interfering RNA targeting hsa_circ_0007334. RESULTS: STAMBP was overexpressed in the tumor tissues as compared with the tumor-adjacent tissues from PC patients. Higher STAMBP expression in the tumor tissues showed worse prognosis. Loss/gain-of-function experiments revealed that STAMBP promoted the malignant behaviors of PC cells in vitro and xenograft tumor growth in vivo. Activation of NF-κB in PC cells was triggered by STAMBP. However, inactive mutants of STAMBP lost these biological functions in PC. hsa_circ_0007334, an oncogene in PC progression, was found to up-regulate STAMBP expression in PC cells. STAMBP up-regulation reversed the effects of hsa_circ_0007334 silencing on cell mobility. CONCLUSIONS: These results indicated that STAMBP depended on its deubiquitinase activities to induce the malignant behaviors of PC cells and was involved in the regulatory mechanism of hsa_circ_0007334 on PC cell mobility. Our findings provide a novel insight into the molecular mechanism of PC.

Fabricating High-Thermal-Conductivity, High-Strength, and High-Toughness Polylactic Acid-Based Blend Composites via Constructing Multioriented Microstructures.

The massive accumulation of plastic waste has caused a serious negative impact on the human living environment. Replacing traditional petroleum-based polymers with biobased and biodegradable poly(l-lactic acid) (PLLA) is considered an effective way to solve this problem. However, it is still a great challenge to manufacture PLLA-based composites with high thermal conductivity and excellent mechanical properties via tailoring the microstructures of the blend composites. In the present work, a melt extrusion-stretching method is utilized to fabricate biodegradable PLLA/poly(butylene adipate-co-butylene terephthalate)/carbon nanofiber (PLLA/PBAT/CNF) blend composites. It is found that the incorporation of the extensional flow field induces the formation of multioriented microstructures in the composites, including the oriented PLLA molecular chains, elongated PBAT dispersed phase, and oriented CNFs, which synergistically improve the thermal conductivity and mechanical properties of the blend composites. At a CNF content of 10 wt %, the in-plane thermal conductivity, tensile strength, and elongation at break of the blend composite reach 1.53 Wm-1 K-1, 66.8 MPa, and 56.5%, respectively, which increased by 31.9, 73.5, and 874.1% compared with those of the conventionally hot-compressed sample (1.16 Wm-1 K-1, 38.5 MPa, and 5.8%, respectively). The main mechanism for the improved thermal conductivity is that the multioriented structure promotes the formation of a CNF thermal conductive network in the composites. The strengthening mechanism is attributed to the orientation of both PLLA molecular chains and CNFs in the stretching direction, restricting the movement of PLLA molecular segments around CNFs, and the toughening mechanism is due to the transformation of PLLA molecular chains from low-energy gt conformers to high-energy gg conformers induced by extensional flow field. More interestingly, after the extrusion-stretched samples are annealed, the oriented PLLA molecular chains form oriented crystal structures such as extended-chain lamellae, common "Shish-kebabs," and hybrid Shish-kebabs, which further enhance the thermal conductivity and heat resistance of the samples. This work reveals the effects of the orientation of the matrix molecular chains and crystallites on the thermal conductivity and mechanical properties of composites and provides a new way to prepare high-performance PLLA-based composites with high thermal conductivity, excellent mechanical properties, and high heat resistance.

A robust molecularly imprinted electrochemiluminescence sensor based on a Ni-Co nanoarray for the sensitive detection of spiramycin.

To prepare portable and robust sensors for the sensitive and selective detection of small molecules is still a challenge for the study of electroanalytical sensors. Here, we developed a molecularly imprinted electrochemiluminescence sensor (MIECL) for the detection of spiramycin (SPI), a type of multi-component macrolide antibiotic. First, Ni-Co LDH nanoarrays were synthesized by a one-step hydrothermal method and then directly used as a sensing platform. Then, as-synthesized N-Ti3C2 was modified on the nanoarrays. Due to the functional nanomaterial N-Ti3C2 not only serving as a substrate material to enable loading a large amount of perylene tetracarboxylic acid (PTCA) but also acting as a co-reaction promoter to accelerate the decomposition of S2O82- to generate more SO4˙-, the modified nanoarrays displayed a significantly enhanced electrochemiluminescence (ECL) signal. Finally, the molecularly imprinted polymer (MIP) and ECL techniques were combined to greatly improve the selectivity and sensitivity of the sensor. Under the optimal conditions, the easily constructed MIECL sensor showed good selectivity, reproducibility, and stability, and a detection limit of up to 3.14 × 10-13 M. The as-fabricated sensor was further evaluated by applying it to detect SPI in milk samples.

Whole-genome sequencing of Mycobacterium tuberculosis for prediction of drug resistance.

Whole-genome sequencing (WGS) has shown tremendous potential in rapid diagnosis of drug-resistant tuberculosis (TB). In the current study, we performed WGS on drug-resistant Mycobacterium tuberculosis isolates obtained from Shanghai (n = 137) and Russia (n = 78). We aimed to characterise the underlying and high-frequency novel drug-resistance-conferring mutations, and also create valuable combinations of resistance mutations with high predictive sensitivity to predict multidrug- and extensively drug-resistant tuberculosis (MDR/XDR-TB) phenotype using a bootstrap method. Most strains belonged to L2.2, L4.2, L4.4, L4.5 and L4.8 lineages. We found that WGS could predict 82.07% of phenotypically drug-resistant domestic strains. The prediction sensitivity for rifampicin (RIF), isoniazid (INH), ethambutol (EMB), streptomycin (STR), ofloxacin (OFL), amikacin (AMK) and capreomycin (CAP) was 79.71%, 86.30%, 76.47%, 88.37%, 83.33%, 70.00% and 70.00%, respectively. The mutation combination with the highest sensitivity for MDR prediction was rpoB S450L + rpoB H445A/P + katG S315T + inhA I21T + inhA S94A, with a sensitivity of 92.17% (0.8615, 0.9646), and the mutation combination with highest sensitivity for XDR prediction was rpoB S450L + katG S315T + gyrA D94G + rrs A1401G, with a sensitivity of 92.86% (0.8158, 0.9796). The molecular information presented here will be of particular value for the rapid clinical detection of MDR- and XDR-TB isolates through laboratory diagnosis.

Levothyroxine treatment for congenital hypothyroidism based on thyroid function: a 10-year clinical retrospective study.

OBJECTIVE: To explore the appropriate dosage of levothyroxine treatment for congenital hypothyroidism patients with different thyroid stimulating hormone (TSH) levels. METHODS: A total of 116 patients, who were regularly followed-up in our endocrine clinic from January 2010 to December 2020, were divided into four groups based on their thyroid function (group A: TSH ≥ 100 mIU/L, group B: TSH ≥ 20, and < 100, group C: TSH > 4.6 mIU/L and < 20 mIU/L with free thyroxine (FT4) < 6.6 pmol/L, and group D: TSH > 4.6 mIU/L and < 20 mIU/L with FT4 > 6.6 pmol/L). The initial dosage of levothyroxine was individualized for each patient based on their TSH level and then adjusted according to their thyroid function at every follow-up time point. The levothyroxine dosage at each time point was compared between the groups, and thyroid function and physical and neurological development after treatment were also compared. RESULTS: After individualized dosage adjustment, all patients achieved normal thyroid function. Although there were statistical differences in neurological development between the four groups (p < 0.05), development was within the normal range for all groups. CONCLUSION: An individualized levothyroxine dosage can provide the same therapeutic effect compared to the recommended dosage. This strategy may also reduce the risk of a drug overdose.