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Severe fever with thrombocytopenia syndrome (SFTS) is a viral hemorrhagic fever caused by a tick-borne virus SFTSV with a mortality rate of up to 30%. Currently, there is no vaccine or effective therapy for SFTS. Neutralizing monoclonal antibody therapy, which provides immediate passive immunity and may limit disease progression, has emerged as a reliable approach for developing therapeutic drugs for SFTS. In this study, 4 human monoclonal antibodies (hmAbs) derived from convalescent SFTS patients' lymphocytes based on human single-chain variable fragment antibody libraries were tested for their neutralizing activities in cells and their treatment effect in animals individually and in pair combinations. The neutralization test showed that all 4 hmAbs exhibited strong neutralizing activity against SFTSV infection in vitro. The protection rate of hmAbs 4-6, 1F6, 1B2, and 4-5 against SFTSV lethal challenge in IFNAR1-/- A129 mice are 50%, 16.7%, 83.3%, and 66.7%, respectively. Notably, the pair combination of antibodies (1B2 and 4-5, 1B2 and 1F6) that recognized distinct epitopes protected 100% of mice against SFTSV lethal challenge. In conclusion, our findings indicate that the pair combinations of hmAbs 1B2 and 4-5 or hmAbs 1B2 and 1F6 may serve as promising therapeutic drugs for treating SFTSV infection.

Middle and low frequency band sound waves have strong penetration and diffraction abilities during the propagation process, making it difficult to attenuate. The control of middle and low frequency broadband sound waves has become a challenging topic. Therefore, it is necessary to develop new materials or structures with middle and low frequency sound absorption, insulation, and noise reduction functions. The special properties of acoustic metamaterial provide new ideas for the development of sound absorption and insulation. In order to effectively control the noise in the lower frequency band, a new spatial spiral acoustic metamaterial was designed. First, the mechanism of band gap characteristics of a new spatial spiral acoustic metamaterial is analyzed. Then, a new spatial spiral acoustic metamaterial is completed through the finite element software COMSOL Multiphysics and the calculation and analysis of sound absorption and insulation performance in the 100–2500 Hz frequency band are completed. With the help of 3D printing, the preparation of metamaterial is completed, and the comparative experimental study of sound absorption and insulation performance of spiral acoustic metamaterial is carried out to verify the accuracy of the calculation method.

Ormosia is a genus of the Fabaceae family that shows a distinct evolutionary history due to its typical Asian-American tropical disjunction distribution pattern. However, both its phylogeny and biogeographic mechanisms have not been fully resolved. In addition, Ormosia species have great economic and ecological potential in the wood and handicraft (using their attractive seeds) industries, reforestation, and folk medicine (due to their flavonoids, alkaloids, and terpenoids), making them highly valuable in research, especially from a genomic perspective. We report the genome assemblies of two common Ormosia species, Ormosia emarginata and Ormosia semicastrata, in South China, using both long and short sequencing reads. The genome assemblies of O. emarginata and O. semicastrata comprised 90 contigs with a total length of 1,420,917,605 bp and 63 contigs with a total length of 1,511,766,959 bp, respectively. Benchmarking Universal Single-Copy Orthologs (BUSCO) assessment revealed 97.0% and 98.3% completeness of the O. emarginata and O. semicastrata assemblies, respectively. The assemblies contain 48,599 and 52,067 protein-coding genes, respectively. Phylogenetic analyses using 1032 single-copy genes with 19 species indicated that they are closely related to Lupinus albus. We investigated genes related to plant hormones, signaling, the circadian rhythm, transcription factors, and secondary metabolites derived from the whole genome and tandem and proximal duplications, indicating that these duplications should play important roles in the growth, development, and defense of Ormosia species. To our knowledge, our study is the first report on Ormosia genome assemblies. This information will facilitate phylogenetic and biogeographic analyses and species breeding in the future.

Abstract Background LL-37 peptide is a member of the human cathelicidin family, and has been shown to promote the healing of pressure ulcers. However, the low stability of this peptide within the wound environment limits its clinical use. Chitosan (CS) hydrogel is commonly used as a base material for wound dressing material. Methods CS hydrogel (2.5% w/v) was encapsulated with LL-37. Cytotoxicity of the product was examined in cultured NIH3T3 fibroblasts. Effects on immune response was examined by measuring tumor necrosis factor-α (TNF-α) release from RAW 264.7 macrophages upon exposure to lipopolysaccharides. Antibacterial activity was assessed using Staphylococcus aureus. Potential effect on pressure ulcers was examined using a mouse model. Briefly, adult male C57BL/6 mice were subjected to skin pressure using magnets under a 12/12 h schedule for 21 days. Mice were randomized to receive naked LL-37 (20 μg), chitosan gel containing 20-μg LL-37 (LL-37/CS hydrogel) or hydrogel alone under the ulcer bed (n = 6). A group of mice receiving no intervention was also included as a control. Results LL-37/CS hydrogel did not affect NIH3T3 cell viability. At a concentration of 1–5 μg/ml, LL-37/CS inhibited TNF-α release from macrophage. At 5 μg/ml, LL-37/CS inhibited the growth of Staphylococcus aureus. The area of the pressure ulcers was significantly lower in mice receiving LL-37/CS hydrogel in comparison to all other 3 groups on days 11 (84.24% ± 0.25%), 13 (56.22% ± 3.91%) and 15 (48.12% ± 0.28%). Histological examination on days 15 and 21 showed increased epithelial thickness and density of newly-formed capillary with naked LL-37 and more so with LL-37/CS. The expression of key macromolecules in the process of angiogenesis (i.e., hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor-A (VEGF-A)) in wound tissue was increased at both the mRNA and protein levels. Conclusion Chitosan hydrogel encapsulated with LL-37 is biocompatible and could promote the healing of pressure ulcers.

BackgroundCOVID-19 has caused more than 2.6 billion infections and several million deaths since its outbreak 2 years ago. We know very little about the long-term cellular immune responses and the kinetics of neutralizing antibodies (NAbs) to SARS-CoV-2 because it has emerged only recently in the human population.MethodsWe collected blood samples from individuals who were from the first wave of the COVID-19 epidemic in Wuhan between December 30, 2019, and February 24, 2020. We analyzed NAbs to SARS-CoV-2 using pseudoviruses and IgG antibodies to SARS-CoV-2 spike (S) and nucleocapsid (N) protein using enzyme-linked immunosorbent assay in patients’ sera and determined SARS-CoV-2-specific T-cell responses of patients with ELISpot assays.ResultsWe found that 91.9% (57/62) and 88.9% (40/45) of COVID-19 patients had NAbs against SARS-CoV-2 in a year (10–11 months) and one and a half years (17–18 months), respectively, after the onset of illness, indicating that NAbs against SARS-CoV-2 waned slowly and possibly persisted over a long period time. Over 80% of patients had IgG antibodies to SARS-CoV-2 S and N protein one and a half years after illness onset. Most patients also had robust memory T-cell responses against SARS-CoV-2 one and a half years after the illness. Among the patients, 95.6% (43/45) had an IFN-γ-secreting T-cell response and 93.8% (15/16) had an IL-2-secreting T-cell response. The T-cell responses to SARS-CoV-2 were positively correlated with antibodies (including neutralizing antibodies and IgG antibodies to S and N protein) in COVID-19 patients. Eighty percent (4/5) of neutralizing antibody-negative patients also had SARS-CoV-2-specific T-cell response. After long-term infection, protective immunity was independent of disease severity, sex, and age.ConclusionsWe concluded that SARS-CoV-2 infection elicited a robust and persistent neutralizing antibody and memory T-cell response in COVID-19 patients, indicating that these sustained immune responses, among most SARS-CoV-2-infected people, may play a crucial role in protection against reinfection.

Patients with extranodal natural killer/T-cell lymphoma (ENKTL), nasal type are benefit from peg-asparaginase, gemcitabine, and methotrexate. Therefore, we conducted a prospective phase II trial using a combination of these drugs as GAD-M regimen in naïve ENKTL patients, simultaneously, explored the combinational mechanism. The GAD-M regimen was administered for 6 cycles sandwiched by radiotherapy for stage I/II and 6 cycles for stage III/IV patients. After 6 cycles, the overall response rate of 36 patients was 91.6%, and the complete remission rate increased to 83.3%. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 74.8% and 77.8%, respectively. The 5-year PFS and OS were 68.3% and 77.8%. No patient suffered from the central nervous system (CNS) relapse. Most patients experienced recoverable liver dysfunction and anemia in this study. The plasma MTX concentration ratio at 12 to 24 hr during the first cycle could be an early predictor of outcomes in ENKTL (PFS, P=0.005; OS, P=0.002). Additionally, we found that high dose MTX (HD-MTX) and gemcitabine had the synergistic effect of ENKTL cell in vitro. Mechanistically, we demonstrated that the combination could lead to obviously apoptosis in ENKTL cell with extremely release of reactive oxygen spices (ROS), which mediated by endoplasmic reticulum stress. In conclusion, the GAD-M regimen could be a new choice to newly diagnosed ENKTL, especially for stage I/II patients. Furthermore, our results showed the synergy effect of HD-MTX with gemcitabine in ENKTL.Clinical Trial RegistrationThis trial was registered at www.clinicaltrials.gov as #NCT01991158.

To address energy shortage and environmental pollution, scientists are working to develop methods for the production, conversion, and storage of new energy sources. The development of thermal energy storage (TES) is considered to be one of the most effective energy conservation and environmental protection strategies for utilizing various renewable energy sources. Energy storage technology can solve the contradiction between energy supply and demand in time and space and also improve energy efficiency. Currently, TES includes mainly sensible heat storage, latent heat storage, and thermochemical energy storage. The latent heat TES based on phase change materials (PCMs) is an efficient technology that is being actively pursued owing to high storage density in a small temperature region, which is essential for accelerating new energy development and improving energy efficiency. In this paper, hydroxyapatite aerogels with self-supporting network structure were prepared via a hydrothermal method using calcium oleate as a precursor. Self-supporting hydroxyapatite-based composite phase change materials were synthesized using the impregnation method. The morphology and thermal properties of the prepared composite phase change materials were characterized and tested by scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetry, and differential scanning calorimetry. The experimental results show that the composite phase change materials of hydroxyapatite aerogels loaded with octadecanol or paraffin have good thermal properties. The measured values of melting enthalpy and solidified enthalpy of the 60% paraffin@HAP composite phase change materials are 85.10 and 85.30 J·g−1, respectively, and its crystallinity is 81.50%. The measured values of melting enthalpy and solidified enthalpy of the 60% octadecanol@HAP composite phase change material are 113.78 and 112.25 J·g−1, respectively, and its crystallinity is 86.20%. In addition, the composite has good thermal and chemical stability. Furthermore, the hydroxyapatite substrate has the advantages of good flame retardancy, corrosion-free characteristics, safety, and environmental protection, which effectively expands the practical application of phase change materials in the field of intelligent thermal insulation textiles and building materials.

Osteosarcoma is a malignant primary bone tumor commonly occurring in children and adolescents. The treatment of local osteosarcoma is mainly based on surgical resection and chemotherapy, whereas the improvement of overall survival remains stagnant, especially in recurrent or metastatic cases. Tumor microenvironment (TME) is closely related to the occurrence and development of tumors, and macrophages are among the most abundant immune cells in the TME. Due to their vital roles in tumor progression, macrophages have gained increasing attention as the new target of tumor immunotherapy. In this review, we present a brief overview of macrophages in the TME and highlight the clinical significance of macrophages and their roles in the initiation and progression of osteosarcoma. Finally, we summarize the therapeutic approaches targeting macrophage, which represent a promising strategy in osteosarcoma therapies.

Background: Natural killer/T-cell lymphoma (NKTCL) is a highly aggressive lymphoma with a dismal prognosis, and novel therapeutic targets are urgently needed. Programmed death-ligand 1 (PD-L1) has become a promising therapeutic target for various cancers, but most of the studies have focused on expression of PD-L1 on tumor cells. Expression of PD-L1 on tumor-infiltrating non-malignant cells, especially monocytes, has not been studied in NKTCL, and its prognostic value remains unknown.Materials and Methods: Expression of PD-L1 on tumor-infiltrating stromal cells was measured in NKTert and HS5 cells when cultured alone or co-cultured with NKTCL cell lines. Clinical samples were collected from 42 patients with newly diagnosed NKTCL. Expression of PD-L1 on monocytes was analyzed in patients' peripheral blood and tumor tissues using flow cytometry and immunofluorescent staining, respectively. Survival data were retrospectively collected and the prognostic significance of PD-L1 expression on monocytes was analyzed.Results: PD-L1 expression on tumor-infiltrating stromal cells was remarkably elevated when co-cultured with NKTCL cells. The percentage of PD-L1+ monocytes among all monocytes in peripheral blood was significantly higher in NKTCL patients than that in healthy individuals. Among NKTCL patients, percentage of PD-L1+ monocytes in blood positively correlated with that in tumor tissues. Patients with a higher percentage (≥78.2%) of PD-L1+ monocytes in blood or with a higher percentage (≥24.2%) of PD-L1+ monocytes in tumor tissues exhibited a significantly inferior survival, compared with their counterparts. A higher percentage of PD-L1+ monocytes in blood or tumor tissues was an independent adverse prognostic factor.Conclusions: Expression of PD-L1 on monocytes is up-regulated and has significant prognostic value in patients with NKTCL.

Xinyang Maojian (XYMJ) green tea is one of the top ten teas in China, and the consumers prefer spring tea due to its umami taste and pleasurable aroma. However, the knowledge about temporal variation of the volatile compounds in XYMJ green teas harvested during different seasons is very limited. In the present work, the main non-volatile compounds that endowed the taste and volatile compounds responsible for the aroma in XYMJ green teas harvested during the spring and autumn seasons were determined. The average contents of free amino acids (FAA) were significantly higher and gradually declined in the spring teas, whereas the caffeine was significantly lower and gradually increased in the spring teas. A total of 39 volatile compounds of six chemical classes were detected in XYMJ green teas, and they displayed various change trends during the spring and autumn seasons, among which 15 volatile compounds were identified as the key odorants based on odor activity value (OAV). The highest OAV of 2195.05 was calculated for the violet-like smelling trans-β-ionone followed by decanal, nonanal, dimethyl sulfide, linalool, geraniol and naphthalene. The OAVs of geraniol, (Z)-3-hexenyl hexanoate, heptanal, benzaldehyde and hexanal in XYMJ spring teas were higher than XYMJ autumn teas. The hierarchical clustering analysis indicated that XYMJ green teas were divided into three clusters and the quality of XYMJ green teas changed greatly within spring season. Harvest season is a crucial factor affecting the flavor quality of XYMJ green teas.

Abstract Primary breast diffuse large B‐cell lymphoma (PB‐DLBCL) is an uncommon extranodal non‐Hodgkin's lymphoma (NHL), which was traditionally treated with anthracycline‐containing regimens followed by consolidative radiation therapy (RT) to add therapeutic benefits. The introduction of anti‐CD20 antibody rituximab for the treatment of B‐cell NHLs has significantly improved the clinical outcome of these malignant diseases. It is unclear, however, whether consolidative RT could still add therapeutic benefits for PB‐DLBCL patients treated with rituximab. To answer this important question, we used the Surveillance, Epidemiology, and End Results (SEER) database to evaluate the impact of RT on the clinical outcomes of PB‐DLBCL patients in the rituximab era. Information on patient age, year of diagnosis, stage, race, laterality, and RT status for PB‐DLBCL patients diagnosed between 2001 and 2014 were extracted. Kaplan–Meier survival curves were plotted, and log‐rank test was used to compare the potential survival difference. Multivariate analysis using Cox proportional hazards model was employed to determine the impact of RT and other factors such as age, race, tumor laterality, stage, and year of diagnosis on survival. Among the 386 patients identified, the median follow‐up time was 45 months (range, 0–167 months); the median age was 64 years (range, 19–93 years); 33.9% of the patients were younger than 60 years of age; 69.9% of the patients were stage I; 79.0% were white; 51.8% received RT. The 5‐year OS and cause‐specific survival (CSS) for the whole cohort were 72.3% and 82.5%, respectively. The 5‐year OS was significantly superior for patients who received RT compared to those who did not receive RT (78.1% vs. 66.0%, P = 0.031). In multivariable analysis, RT remained significantly associated with improved OS (P = 0.026). In summary, our study suggests that RT still adds significant therapeutic benefits for patients with PB‐DLCBL in the rituximab era.

Qingzhuan tea (QZT) is a typical Chinese dark tea that has a long-time manufacturing process. In the present study, liquid chromatography coupled with tandem mass spectrometry was used to study the chemical changes of tea samples during QZT processing. Untargeted metabolomics analysis revealed that the pile-fermentation and turnover (post-fermentation, FT) was the crucial stage in transforming the main compounds of QZT, whose contents of flavan-3-ols and flavonoids glycosides were decreased significantly. The bioactivities, including the antioxidant capacities and inhibitory effects on α-amylase and α-glucosidase, were also reduced after the FT process. It was suggested that although the QZT sensory properties improved following pile-fermentation and aging, the bioactivities remained restrained. Correlation analysis indicated that the main galloylated catechins and flavonoid glycosides were highly related to their antioxidant capacity and inhibitory effects on α-amylase and α-glucosidase.

Abstract Background As a surrogate marker of systemic inflammation, the lymphocyte-to-monocyte ratio (LMR) is an independent prognostic factor for various malignancies. This study investigated the prognostic significance of the pre-chemotherapy LMR in patients with previously untreated metastatic colorectal cancer (mCRC) receiving chemotherapy. Methods The present study included newly diagnosed mCRC patients treated between January 2005 and December 2013 with FOLFOX chemotherapy, specifically oxaliplatin 180 mg/m2 on day 1, with leucovorin 400 mg/m2 administered as a 2-hour infusion before the administration of 5-fluorouracil 400 mg/m2 as an intravenous bolus injection, and 5-fluorouracil 2400 mg/m2 as a 46-h infusion immediately after 5-fluorouracil bolus injection. The LMR was calculated as the absolute count of lymphocytes divided by the absolute count of monocytes. COX proportional hazards analysis was performed to evaluate the association of LMR with survival outcomes. Results A total of 488 patients were included. Patients with high pre-chemotherapy LMR experienced significant improvements in progression-free survival (PFS, 9.2 vs. 7.6 months, P

A variable metric method based gradient pursuit algorithm based on some existing gradient pursuit algorithms was proposed by combining the gradient direction of optimization methods with greedy algorithms.The computational complexity and storage requirements of these algorithms were also analysed and compared.In experimental part,all these algorithms were used to reconstruct one-dimensional audio signal and two-dimensional image signal.Experimental results show that the VMMGP algorithm has the best reconstruction performance among all the gradient pursuit algorithms.

A variable metric method based gradient pursuit algorithm based on some existing gradient pursuit algorithms was proposed by combining the gradient direction of optimization methods with greedy algorithms.The computational complexity and storage requirements of these algorithms were also analysed and compared.In experimental part,all these algorithms were used to reconstruct one-dimensional audio signal and two-dimensional image signal.Experimental results show that the VMMGP algorithm has the best reconstruction performance among all the gradient pursuit algorithms.

Pretreatment plasma D-dimer levels have been reported to predict survival in several types of malignancies. The aim of this study was to evaluate the prognostic value of D-dimer levels in patients with newly diagnosed natural killer/T-cell lymphoma (NKTCL). The cut-off value of D-dimer to predict survival was set as 1.2 μg/mL based on the receiver operating curve analysis. Patients with a D-dimer level ≥ 1.2 μg/mL had significantly more adverse clinical features, including poor performance status, advanced stage diseases, B symptoms, elevated serum lactic dehydrogenase levels, involvement of regional lymph nodes, more extranodal diseases, and higher International Prognostic Index and natural killer/T-cell lymphoma prognostic index scores. A D-dimer level ≥ 1.2 μg/mL was significantly associated with inferior 3-year overall survival (OS, 13.0 vs. 68.5%, P < 0.001). In the multivariate analysis, a D-dimer level ≥ 1.2 μg/mL remained an independent predictor for worse OS (HR: 3.13, 95% CI: 1.47-6.68, P = 0.003) after adjusting for other confounding prognostic factors. Among patients with Ann Arbor stage I-II diseases, those with a D-dimer level ≥ 1.2 μg/mL had a significantly worse survival than those with a D-dimer level < 1.2 μg/mL (3 year-OS: 76.2 vs. 22.2%, P < 0.001). Survival of early-stage patients with a high D-dimer level was similar to that of the advanced-stage patients. In conclusion, pretreatment plasma D-dimer level may serve as a simple but effective predictor of prognosis in patients with NKTCL.

The goal of our study is to investigate the contribution of promoter DNA methylation of α-adducin (ADD1) gene to the risk of essential hypertension (EH). Using the bisulphite pyrosequencing technology, DNA methylation levels of five CpG dinucleotides on ADD1 promoter were measured among 33 EH cases and 28 healthy controls. Significantly higher ADD1 DNA methylation levels were observed in the females than in the males (CpG1: P = 0.016; CpG2-5: P = 0.021). A breakdown analysis by gender showed that lower CpG1 methylation was associated with an increased risk of EH in females (adjusted P = 0.042). A much more significant association between lower CpG2-5 methylation levels and the increased risk of EH was found in males (adjusted P = 0.008). CpG1 methylation was inversely correlated with age in females (r = -0.407, P = 0.019) but not in males. ADD1 CpG1 and CpG2-5 methylation levels were significantly lower in post-menopausal (>50 years) women than pre-menopausal (≤50 years) women (CpG1: P = 0.006; CpG2-5: P = 0.034). A significant interaction between CpG1 methylation and age was found in females (CpG1*age: P = 0.029). CpG2-5 methylation was shown as a significant predictor of EH in males [area under curve (AUC) = 0.855, P = 0.001], in contrast that CpG1 methylation was a trend toward indicator in females (AUC = 0.699, P = 0.054). In addition, significant differences were observed between males and females for alanine aminotransferase (ALT, P = 0.001), aspartate aminotransferase (AST, P = 0.005) and uric acid (P

Background Haemorrhages of brainstem cavernous malformations (CMs) can lead to neurological deficits, the natural history of which is uncertain. The study aimed to evaluate the neurological outcomes of untreated brainstem CMs and to identify the adverse factors associated with worsened outcomes.Methods From 2009 to 2015, 698 patients (321 women) with brainstem CMs were entered into the prospective cohort after excluding patients lost to follow-up (n=43). All patients were registered, clinical data were collected and scheduled follow-up was performed.Results After a median follow-up of 60.9 months, prospective haemorrhages occurred in 167 patients (23.9%). The mean modified Rankin Scale scores at enrolment and at censoring time were 1.6 and 1.2. Neurological status was improved, unchanged and worsened in 334 (47.9%), 293 (42.0%) and 71 (10.2%) patients, respectively; 233 (33.4%) recovered to normal levels. Lesions crossing the axial midpoint (relative risk (RR) 2.325, p=0.003) and developmental venous anomaly (DVA) (RR 1.776, p=0.036) were independently significantly related to worsened outcomes. The percentage of worsened outcomes was 5.3% (18 of 337) in low-risk patients (neither DVA nor crossing the axial point) and increased to 26.0% (13 of 50) in high-risk patients (with both DVA and crossing the axial point). The percentage of worsened outcomes significantly increased as the number of prospective haemorrhages increased (from 1.5% (8 of 531, if 0 prospective ictus) to 37.5% (48 of 128, if 1 ictus) and 38.5% (15 of 39, if >1 ictus)).Conclusions The neurological outcomes of untreated brainstem CMs were improved/unchanged in majority of patients (89.8%) with a fatality rate of 1.7% in our cohort, which seemed to be favourable. Radiological features significantly predicted worsened outcomes. Our results provide evidence for clinical consultation and individualised treatment. The referral bias of our cohort was underlined.

Methyl vinyl silicone rubber and methyl vinyl phenyl silicone rubber were used as the matrix, silica and boron phenolic resin (BF) were added for mixing, a light ablative heat insulation material was prepared. The density of the heat insulation material, the ablative performance of the heat insulation material under oxygen-acetylene flame and the back temperature of the material in the ablative process were studied. The results showed that with the addition of BF, the density of thermal insulation materials decreased significantly. When the amount of BF was 40 phr and 50 phr (mass, the same below), the density was 0.816 7 g/cm3 and 0.752 8 g/cm3 respectively, which was 29.35% and 34.88% lower than that without BF. With the increasing amount of BF, the mass ablation rate and linear ablation rate of the thermal insulation material increased, but the addition of BF could enhance the thermal insulation performance of the material. When 40 phr BF were added, the maximum back temperature was only 78 ℃.