Measurements of All-Particle Energy Spectrum and Mean Logarithmic Mass of Cosmic Rays from 0.3 to 30 PeV with LHAASO-KM2A.

We present the measurements of all-particle energy spectrum and mean logarithmic mass of cosmic rays in the energy range of 0.3-30 PeV using data collected from LHAASO-KM2A between September 2021 and December 2022, which is based on a nearly composition-independent energy reconstruction method, achieving unprecedented accuracy. Our analysis reveals the position of the knee at 3.67±0.05±0.15 PeV. Below the knee, the spectral index is found to be -2.7413±0.0004±0.0050, while above the knee, it is -3.128±0.005±0.027, with the sharpness of the transition measured with a statistical error of 2%. The mean logarithmic mass of cosmic rays is almost heavier than helium in the whole measured energy range. It decreases from 1.7 at 0.3 PeV to 1.3 at 3 PeV, representing a 24% decline following a power law with an index of -0.1200±0.0003±0.0341. This is equivalent to an increase in abundance of light components. Above the knee, the mean logarithmic mass exhibits a power law trend towards heavier components, which is reversal to the behavior observed in the all-particle energy spectrum. Additionally, the knee position and the change in power-law index are approximately the same. These findings suggest that the knee observed in the all-particle spectrum corresponds to the knee of the light component, rather than the medium-heavy components.

Measurement of Ultra-High-Energy Diffuse Gamma-Ray Emission of the Galactic Plane from 10 TeV to 1 PeV with LHAASO-KM2A.

The diffuse Galactic γ-ray emission, mainly produced via interactions between cosmic rays and the interstellar medium and/or radiation field, is a very important probe of the distribution, propagation, and interaction of cosmic rays in the Milky Way. In this Letter, we report the measurements of diffuse γ rays from the Galactic plane between 10 TeV and 1 PeV energies, with the square kilometer array of the Large High Altitude Air Shower Observatory (LHAASO). Diffuse emissions from the inner (15°10 TeV). The energy spectrum in the inner Galaxy regions can be described by a power-law function with an index of -2.99±0.04, which is different from the curved spectrum as expected from hadronic interactions between locally measured cosmic rays and the line-of-sight integrated gas content. Furthermore, the measured flux is higher by a factor of ∼3 than the prediction. A similar spectrum with an index of -2.99±0.07 is found in the outer Galaxy region, and the absolute flux for 10≲E≲60 TeV is again higher than the prediction for hadronic cosmic ray interactions. The latitude distributions of the diffuse emission are consistent with the gas distribution, while the longitude distributions show clear deviation from the gas distribution. The LHAASO measurements imply that either additional emission sources exist or cosmic ray intensities have spatial variations.

A tera-electron volt afterglow from a narrow jet in an extremely bright gamma-ray burst.

Some gamma-ray bursts (GRBs) have a tera-electron volt (TeV) afterglow, but the early onset of this has not been observed. We report observations with the Large High Altitude Air Shower Observatory (LHAASO) of the bright GRB 221009A, which serendipitously occurred within the instrument's field of view. More than 64,000 photons >0.2 TeV were detected within the first 3000 seconds. The TeV flux began several minutes after the GRB trigger and then rose to a peak ~10 seconds later. This was followed by a decay phase, which became more rapid ~650 seconds after the peak. We interpret the emission using a model of a relativistic jet with half-opening angle of ~0.8°. This is consistent with the core of a structured jet and could explain the high isotropic energy of this GRB.

[A preliminary study on salivary microbiota of patients with laryngopharyngeal reflux].

Objective: To investigate the characteristics of salivary microbiota in patients with laryngopharyngeal reflux (LPR). Methods: A case-control study was applied to enroll 60 patients and healthy subjects who were outpatients of the Department of Otorhinolaryngology Head and Neck Surgery of the Eighth Medical Center of the PLA General Hospital from December 2020 to March 2021, including 35 males and 25 females, aged from 21 to 80 (33.75±11.10) years. Thirty patients with suspected laryngopharyngeal reflux were selected as study group and thirty healthy volunteers without pharyngeal symptoms were selected as control group. Their salivary samples were collected, and the salivary microbiota was detected and analyzed by 16S rDNA sequencing. SPSS 18.0 software was used for statistical analysis. Results: There was no significant difference in the diversity of salivary microbiota between the two groups. At the phylum classification level, the relative abundance of Bacteroidetes in the study group was higher than that in the control group[37.86(31.15, 41.54)% vs 30.24(25.51, 34.18)%,Z=-3.46,P<0.01]. And the relative abundance of Proteobacteria in the study group was lower than that in the control group [15.76(11.81, 20.17)% vs 20.63(13.98, 28.82)%, Z=-1.98,P<0.05]. At the genus level, the relative abundance of Prevotella, Lactobacillus, Parascardovia and Sphingobium in the study group was higher than that in the control group(Z values were-2.92, -2.69, -2.05, -2.31, respectively, P<0.05).And the relative abundance of Streptococcus, Cardiobacterium, Klebsiella and Uruburuella of study group was lower than that of control group(Z values were -2.43, -2.32, -2.17, -2.32, respectively, P<0.05). LEfSe difference analysis showed that there were 39 bacteria with significant differences between the two groups, including Bacteroidetes, Prevotellaceae and Prevotella, which were enriched in the study group, and Streptococcaceae, Streptococcus and other taxa, which were enriched in the control group(P<0.05). Conclusion: The changes of the microflora in the saliva between LPR patients and healthy people suggest that the dysbacteriosis might exist in LPR patients, which may play an important role in the pathogenesis and development of LPR.

[Knobloch syndrome: a case report].

A 5-year-old girl came to the Tianjin Medical University Eye Hospital in May 2021 because of her poor eyesight after birth. The physical examination showed that she had high myopia, esotropia, horizontal tremor, and high myopia retinopathy of both eyes. After inquiring about her medical history, we found that the baby's occipital cystic mass swelled after birth, and CT examination showed that the occipital skull plate defect with meningocele, but without treatment, at present, the occipital mass had subsided by itself. Considering the eye manifestations and skull changes of the child, it may be conformed to Knobloch syndrome, after the detection of V4 by full exon gene, it was found that the child had the compound heterozygous variation of pathogenic gene COL18A1, and Knobloch syndrome was definite, Knobloch syndrome is a rare autosomal recessive hereditary disease with typical features of high myopia, retinal detachment and occipital encephalocele. At present, there is no clear treatment plan, and gene therapy may be an effective treatment for Knobloch syndrome in the future.

Exploring Lorentz Invariance Violation from Ultrahigh-Energy γ Rays Observed by LHAASO.

Recently, the LHAASO Collaboration published the detection of 12 ultrahigh-energy γ-ray sources above 100 TeV, with the highest energy photon reaching 1.4 PeV. The first detection of PeV γ rays from astrophysical sources may provide a very sensitive probe of the effect of the Lorentz invariance violation (LIV), which results in decay of high-energy γ rays in the superluminal scenario and hence a sharp cutoff of the energy spectrum. Two highest energy sources are studied in this work. No signature of the existence of the LIV is found in their energy spectra, and the lower limits on the LIV energy scale are derived. Our results show that the first-order LIV energy scale should be higher than about 10^{5} times the Planck scale M_{Pl} and that the second-order LIV scale is >10^{-3}M_{Pl}. Both limits improve by at least one order of magnitude the previous results.

Constraints on Heavy Decaying Dark Matter from 570 Days of LHAASO Observations.

The kilometer square array (KM2A) of the large high altitude air shower observatory (LHAASO) aims at surveying the northern γ-ray sky at energies above 10 TeV with unprecedented sensitivity. γ-ray observations have long been one of the most powerful tools for dark matter searches, as, e.g., high-energy γ rays could be produced by the decays of heavy dark matter particles. In this Letter, we present the first dark matter analysis with LHAASO-KM2A, using the first 340 days of data from 1/2-KM2A and 230 days of data from 3/4-KM2A. Several regions of interest are used to search for a signal and account for the residual cosmic-ray background after γ/hadron separation. We find no excess of dark matter signals, and thus place some of the strongest γ-ray constraints on the lifetime of heavy dark matter particles with mass between 10^{5} and 10^{9} GeV. Our results with LHAASO are robust, and have important implications for dark matter interpretations of the diffuse astrophysical high-energy neutrino emission.

Peta-electron volt gamma-ray emission from the Crab Nebula.

The Crab Nebula is a bright source of gamma rays powered by the Crab Pulsar's rotational energy through the formation and termination of a relativistic electron-positron wind. We report the detection of gamma rays from this source with energies from 5 × 10-4 to 1.1 peta-electron volts with a spectrum showing gradual steepening over three energy decades. The ultrahigh-energy photons imply the presence of a peta-electron volt electron accelerator (a pevatron) in the nebula, with an acceleration rate exceeding 15% of the theoretical limit. We constrain the pevatron's size between 0.025 and 0.1 parsecs and the magnetic field to ≈110 microgauss. The production rate of peta-electron volt electrons, 2.5 × 1036 ergs per second, constitutes 0.5% of the pulsar spin-down luminosity, although we cannot exclude a contribution of peta-electron volt protons to the production of the highest-energy gamma rays.

Extended Very-High-Energy Gamma-Ray Emission Surrounding PSR J0622+3749 Observed by LHAASO-KM2A.

We report the discovery of an extended very-high-energy (VHE) gamma-ray source around the location of the middle-aged (207.8 kyr) pulsar PSR J0622+3749 with the Large High-Altitude Air Shower Observatory (LHAASO). The source is detected with a significance of 8.2σ for E>25 TeV assuming a Gaussian template. The best-fit location is (right ascension, declination) =(95.47°±0.11°,37.92°±0.09°), and the extension is 0.40°±0.07°. The energy spectrum can be described by a power-law spectrum with an index of -2.92±0.17_{stat}±0.02_{sys}. No clear extended multiwavelength counterpart of the LHAASO source has been found from the radio to sub-TeV bands. The LHAASO observations are consistent with the scenario that VHE electrons escaped from the pulsar, diffused in the interstellar medium, and scattered the interstellar radiation field. If interpreted as the pulsar halo scenario, the diffusion coefficient, inferred for electrons with median energies of ∼160 TeV, is consistent with those obtained from the extended halos around Geminga and Monogem and much smaller than that derived from cosmic ray secondaries. The LHAASO discovery of this source thus likely enriches the class of so-called pulsar halos and confirms that high-energy particles generally diffuse very slowly in the disturbed medium around pulsars.

Ultrahigh-energy photons up to 1.4 petaelectronvolts from 12 γ-ray Galactic sources.

The extension of the cosmic-ray spectrum beyond 1 petaelectronvolt (PeV; 1015 electronvolts) indicates the existence of the so-called PeVatrons-cosmic-ray factories that accelerate particles to PeV energies. We need to locate and identify such objects to find the origin of Galactic cosmic rays1. The principal signature of both electron and proton PeVatrons is ultrahigh-energy (exceeding 100 TeV) γ radiation. Evidence of the presence of a proton PeVatron has been found in the Galactic Centre, according to the detection of a hard-spectrum radiation extending to 0.04 PeV (ref. 2). Although γ-rays with energies slightly higher than 0.1 PeV have been reported from a few objects in the Galactic plane3-6, unbiased identification and in-depth exploration of PeVatrons requires detection of γ-rays with energies well above 0.1 PeV. Here we report the detection of more than 530 photons at energies above 100 teraelectronvolts and up to 1.4 PeV from 12 ultrahigh-energy γ-ray sources with a statistical significance greater than seven standard deviations. Despite having several potential counterparts in their proximity, including pulsar wind nebulae, supernova remnants and star-forming regions, the PeVatrons responsible for the ultrahigh-energy γ-rays have not yet been firmly localized and identified (except for the Crab Nebula), leaving open the origin of these extreme accelerators.

LncRNA AB073614 promotes tumor migration and invasion by repressing CDKN1A in non-small cell lung cancer.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "LncRNA AB073614 promotes tumor migration and invasion by repressing CDKN1A in non-small cell lung cancer, by W.-D. Zhao, B.-X. Zhang, X.-H. Cui, J. Zhang, N. Du, Y.-F. Zhang, published in Eur Rev Med Pharmacol Sci 2019; 23 (13): 5815-5822-DOI: 10.26355/eurrev_201907_18320-PMID: 31298333" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18320.

[Relationship between sleep status and laryngopharyngeal reflux disease in adult patients in Otolaryngology clinic].

Objective: To explore the correlation between sleep and laryngopharyngeal reflux disease by epidemiological approaches. Methods: From May 1, 2017 to April 30, 2018, data of age, gender, height, weight, smoking, alcohol consumption, constipation and high fat diet in patients in Otorhinolaryngology specialist clinic, the Eighth Medical Center, General Hospital of the Chinese PLA were retrospectively analyzed. Reflux Symptom Index (RSI), Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression Scale (HADS)were filled. According to RSI scores, patients were divided into case group and control group. The differences of the above indicators between the two groups were compared by Stata 12.0 software, and the risk factors of LPRD were analyzed by multivariate Logistic regression. Results: A total of 908 patients were enrolled, including 166 in the case group and 742 in the control group. There was no significant difference in BMI, smoking, drinking, constipation and high fat diet between the two groups (all P>0.05). The PSQI, anxiety and depression score of the case group were higher than those of the control group. The anxiety and depression scores of the patients with sleep disorders in the case group were significantly higher than those of the normal sleepers (all P<0.05). RSI of the patients with sleep disorders was higher than that of the patients with normal sleep(9.5[4.0,16.0]vs. 5.0[1.0,10.0], Z=-6.07, P<0.001). Multivariate analysis showed that sleep disorder was the risk factors of LPRD (OR=2.59, 95%CI 1.75-3.84). Conclusions: Sleep disorder is related to the occurrence of LPRD. The association between LPRD and sleep disturbances is bidirectional. Sleep disorder may also be related to the anxiety and depression in LPRD patients. Handling sleep disorder timely may benefit LPRD patients.

LncRNA AB073614 promotes tumor migration and invasion by repressing CDKN1A in non-small cell lung cancer.

OBJECTIVE: Some researches have showed that long noncoding RNAs (lncRNAs) take part in varieties of biological behaviors during the tumor progression. This study aims to determine whether lncRNA AB073614 functioned in the metastasis of non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was used to detect AB073614 expression in NSCLC tissues. Besides, wound healing assay and transwell assay were conducted in NSCLC cells. Furthermore, the mechanism assays were performed to identify how AB073614 functioned in metastasis of NSCLC cells. RESULTS: By comparing with the expression level in adjacent tissues, the AB073614 expression level in NSCLC samples was significantly higher. Moreover, after AB073614 was knocked down, invasion and migration of NSCLC cells were inhibited. And after AB073614 was overexpressed, invasion and migration of NSCLC cells were promoted. Also, mRNA and protein expression level of CDKN1A was upregulated via knockdown of AB073614, while mRNA and protein expression level of CDKN1A was downregulated via overexpression of AB073614. Besides, the expression of CDKN1A in NSCLC tissues was negatively correlated to the expression of AB073614. CONCLUSIONS: Our results indicated that AB073614 could enhance cell migration and cell invasion in NSCLC through repressing CDKN1A, which might offer a potential therapeutic choice for patients with NSCLC.

RG108 induces the apoptosis of endometrial cancer Ishikawa cell lines by inhibiting the expression of DNMT3B and demethylation of HMLH1.

OBJECTIVE: The effects of DNA methyltransferase (DNMT) inhibitor RG108 on the proliferation and apoptosis of endometrial cancer was investigated, and whether its mechanism was related to the inhibition of DNMT3B, thereby affecting the human mutL homolog 1 (hMLH1) methylation status and its expression, was further studied. MATERIALS AND METHODS: Culture of human endometrial cancer Ishikawa cell lines: cells grew adhering to the wall in Roswell Park Memorial Institute-1640 (RPMI-1640) medium (supplemented with 10% fetal bovine serum (FBS) and 2 mM L-glutamic acid). After the cells were treated with RG108, the changes in cell viability were detected via methyl thiazolyl tetrazolium (MTT) assay. The effect of RG108 on cell cycle was detected via flow cytometry, and its effect on cell apoptosis was detected via flow cytometry and TUNEL. Moreover, the methylation status of hMLH1gene in endometrial cancer cells was detected via methylation specific-PCR (MSP), and the changes in DNMT3Band hMLH1 expressions were detected via RT-PCR and Western blotting, respectively. RESULTS: MTT results showed that RG108 inhibited the cell viability in a dose-dependent and time-dependent manner. Flow cytometry revealed that RG108 blocked the cell cycle in G2/M phase and promoted the apoptosis, and TUNEL assay further proved that RG108 promoted the apoptosis. It was found in the detection via MSP that the methylated hMLH1 gene was significantly reduced after 72 h of treatment with RG108. Besides, RT-PCR and Western blotting showed that RG108 inhibited the DNMT3B expression and activated the hMLH1 expression. CONCLUSIONS: The demethylation drug RG108 can significantly inhibit the proliferation of endometrial cancer cells, block the cell cycle in the G2/M phase and induce the cell apoptosis, which is a new candidate drug in the treatment of endometrial cancer. RG108 realizes the hMLH1 demethylation and increases the hMLH1 expression through inhibiting the expression of DNMT3B.

MiR-133b regulates the expression of CTGF in epithelial-mesenchymal transition of ovarian cancer.

OBJECTIVE: To explore the role of miR-133b in ovarian cancer and to preliminarily elucidate the mechanism of miR-133b in epithelial-mesenchymal transition (EMT) of ovarian cancer. PATIENTS AND METHODS: MiR-133b was detected in ovarian cancer specimens, and the relationship of miR-133b with each pathological index and clinical index of ovarian cancer was analyzed. The action targets of miR-133b in ovarian cancer were analyzed systematically and studied deeply via the target validation and cell function validation. Finally, the possible reasons of ovarian cancer metastasis were analyzed through the molecular regulation mechanism in EMT of ovarian cancer. RESULTS: The miR-133b level in ovarian cancer was significantly lower than in normal ovarian tissues and benign ovarian tumors (p<0.05). The level of miR-133b in ovarian cancer was related to differentiated degree and lymphatic metastasis. Dual-luciferase assay indicated that connective tissue growth factor (CTGF) was the target gene regulated by miR-133b. Reverse transcriptase-polymerase chain reaction (RT-PCR) as well as Western blot results proved that the expression level of E-cadherin representing the epithelial cell phenotype was increased, while the expression level of vimentin representing the mesenchymal cell phenotype was decreased. Transwell assay confirmed that the migration and invasion abilities of ovarian cancer cells declined after transfection with miR-133b plasmid. After co-transfection with miR-133b and CTGF overexpression plasmids, RT-PCR and Western blotting proved that the expression level of E-cadherin representing the epithelial cell phenotype was decreased, while the expression level of vimentin representing the mesenchymal cell phenotype was increased; transwell assay confirmed that the cell migration and invasion abilities were increased after co-transfection. CONCLUSIONS: The results of this study showed that miR-133b may serve as a new molecular marker of EMT of ovarian cancer, and act as a molecular marker of differentiated degree and lymphatic metastasis of ovarian cancer.

Increased human epididymis protein 4 in benign gynecological diseases complicated with chronic renal insufficiency patients.

We examined the serum concentration of human epididymis protein (HE4) in patients with benign gynecological diseases complicated with chronic renal deficiency and its significance in the differential diagnosis of benign and malignant gynecological diseases. Serum HE4 and cancer antigen 125 concentrations were detected by chemiluminescence. Clinically or pathologically confirmed gynecological diseases were grouped and retrospectively analyzed, including 50 cases of gynecological benign diseases, 35 cases of non-mucinous epithelial ovarian carcinoma, 36 cases of endometrial adenocarcinoma, 15 cases of gynecological benign diseases patients complicated with chronic renal deficiency, 15 cases of gynecological diseases without chronic renal deficiency, and 30 normal controls. Serum HE4 values in the ovarian cancer group, endometrial cancer group, gynecological benign diseases with chronic renal deficiency group, and chronic renal deficiency group were significantly increased compared with the benign gynecological diseases and normal control groups, showing a significant difference (P < 0.001). A comparison of 4 groups with high HE4 showed that the HE4 level in the 2 groups with renal deficiency were higher than those in the ovarian cancer and endometrial cancer groups, but the difference was not significant (P > 0.05); there was no significant difference between 2 groups with renal deficiency (P > 0.05). Serum concentration of HE4 was high in patients with chronic renal deficiency, which should be distinguished during differential diagnosis of gynecological benign and malignant tumors in patients with chronic renal deficiency to avoid misdiagnosis.

Sclerotial biomass and carotenoid yield of Penicillium sp. PT95 under oxidative growth conditions and in the presence of antioxidant ascorbic acid.

AIMS: To determine the effect of oxidative stress and exogenous ascorbic acid on sclerotial biomass and carotenoid yield of Penicillium sp. PT95. METHODS: In this experiment, high oxidative stress was applied by the inclusion of FeSO(4) in the growth medium and exposure to light. Low oxidative stress was applied by omitting iron from the growth medium and by incubation in the dark. Supplementation of exogenous ascorbic acid (as antioxidant) to the basal medium caused a concentration-dependent delay of sclerotial differentiation (up to 48 h), decrease of sclerotial biomass (up to 40%) and reduction of carotenoid yield (up to 91%). On the contrary, the exogenous ascorbic acid also caused a concentration-dependent decrease of lipid peroxidation in colonies of this fungus. CONCLUSIONS: Under high oxidative stress growth condition, the sclerotial biomass and carotenoid yield of PT95 strain in each plate culture reached 305 mg and 32.94 microg, which were 1.23 and 3.71 times higher, respectively, than those at low oxidative stress growth condition. These data prompted us to consider that in order to attain higher sclerotial biomass and pigment yield, the strain PT95 should be grown under high oxidative stress and in the absence of antioxidants. SIGNIFICANCE AND IMPACT OF THE STUDY: These results suggest that strain PT95 may be used for solid-state fermentation of carotenoid production under high oxidative stress growth conditions.

DNA methylation patterns in in vitro-fertilised goat zygotes.

Recent studies have shown that zygote demethylation patterns in mammals are variable among species. However, the methylation patterns of goat zygotes have not yet been reported on. In the present study, using immunofluorescence staining with an antibody against 5-methylcytosine, the methylation patterns of in vitro-derived goat zygotes were studied. The results indicate that goat zygotes do not undergo active global demethylation during pronuclei development, which is similar to the situation in ovine, but not in murine or bovine zygotes. This is believed to be the first report regarding methylation in goat zygotes.

[Genotyping of hepatitis C virus in patients with hepatocellular carcinoma].

Forty-two patients with hepatocellular carcinoma (HCC) were examined for hepatitis C virus (HCV) RNA in liver tissues by reverse transcription-polymerase chain reaction (RT PCR). Typing of HCV liver samples of 18 patients was dependent on the amplification of NS5 region by PCR using type-specific primers. Type-II was found in 14 of the 18 patients (78%), 7 of the 18 patients (39%) and 4 of the 18 patients (22%) were positive for type-II and I and for type-II and III or IV (III/IV), respectively. Type V or VI (V/VI) infection was not observed. These data indicate that HCV type-II may be the major type in HCC patients with HCV infection in China, and some patients can be coinfected with type-II and I or III/IV.

[A transposition of iliopsoas in replacement of pelvic floor for incontinence of urination and/or defecation in children].

Fourteen patients, the age ranged from 2 to 12 years, with fecal and/or urinary incontinence were treated between 1991 and 1993 using a transposition of iliopsoas in replacement or strengthening of pelvic floor. The results were encouraging. The evaluation of the function of pelvic floor was described. Levator plays an important role in normal mechanism of defecation as well as urination. Several types of incontinence develop while the disfunction of pelvic floor occur and some function of continence could be restored by an operation of transposition of iliopsoas.