An optimize adaptable method for determining the monosaccharide composition of pectic polysaccharides.

Pectic polysaccharides are considered the highly complex natural plant polysaccharides which plays a vital role in plant tissue structure and human health. Detailed characterization of the monosaccharide composition can provide insights into the pectic polysaccharide structure. Nevertheless, when analyzing the monosaccharides of pectic polysaccharide, it is crucial to address the issue of incomplete hydrolysis that can occur due to the formation of acid-induced precipitates. Based on above, the main purpose of this article is to provide an optimized method for monosaccharide analysis of pectic polysaccharides through acid hydrolysis optimization using high-performance anion exchange chromatography (HPAEC) The results indicate that reducing the sample concentration to 0.5 mg/mL effectively reduces the acid gelling phenomenon and promotes the complete hydrolysis of pectin polysaccharides. The optimized parameters for acid hydrolysis involve 110 °C for 6 h in 2 M TFA. Furthermore, the consistency of this method is assessed, along with its ability to analyze pectin polysaccharides from various fruits. This hydrolysis approach holds promise for enabling accurate quantification of monosaccharide composition in pectic polysaccharides.

Exploring the Chinese public's affective attitudes towards digital transformation in agriculture: A social media-based analysis.

This study utilizes natural language processing techniques and panel vector autoregression methodology, to delve into the perceived attitudes of social media users towards the digital transformation of agriculture, and to assess its impact on total agricultural output and agricultural science and technology inputs. Data related to agricultural digital transformation were collected from Sina Weibo using web crawlers. The SnowNLP model was employed to infer users' attitudes, encompassing both positive and negative aspects. Furthermore, the study delves into the specific themes capturing users' positive attitudes and explores regional variations in focus. The findings reveal a sustained increase in users' interest in agricultural digital transformation since 2013. Positive attitudes primarily center around green development, agricultural intelligence, and global cooperation and innovation. Moreover, the study establishes a significant positive impact of users' positive attitudes on both total agricultural output value and agricultural science and technology investment, highlighting the constructive influence of user support on the agricultural industry's development.

AKT1 Promotes Tumorigenesis and Metastasis by Directly Phosphorylating Hexokinases.

The importance of protein kinase B (AKT) in tumorigenesis and development is well established, but its potential regulation of metabolic reprogramming via phosphorylation of the hexokinase (HK) isozymes remains unclear. There are two HK family members (HK1/2) and three AKT family members (AKT1/2/3), with varied distribution of AKTs exhibiting distinct functions in different tissues and cell types. Although AKT is known to phosphorylate HK2 at threonine 473, AKT-mediated phosphorylation of HK1 has not been reported. We examined direct binding and phosphorylation of HK1/2 by AKT1 and identified the phosphorylation modification sites using coimmunoprecipitation, glutathione pull-down, western blotting, and in vitro kinase assays. Regulation of HK activity through phosphorylation by AKT1 was also examined. Uptake of 2-[1,2-3H]-deoxyglucose and production of lactate were investigated to determine whether AKT1 regulates glucose metabolism by phosphorylating HK1/2. Functional assays, immunohistochemistry, and tumor experiments in mice were performed to investigate whether AKT1-mediated regulation of tumor development is dependent on its kinase activity and/or the involvement of HK1/2. AKT interacted with and phosphorylated HK1 and HK2. Serine phosphorylation significantly increased AKT kinase activity, thereby enhancing glycolysis. Mechanistically, the phosphorylation of HK1 at serine 178 (S178) by AKT significantly decreased the Km and enhanced the Vmax by interfering with the formation of HK1 dimers. Mutations in the AKT phosphorylation sites of HK1 or HK2 significantly abrogated the stimulatory characteristics of AKT on glycolysis, tumorigenesis, and cell migration, invasion, proliferation, and metastasis. HK1-S178 phosphorylation levels were significantly correlated with the occurrence and metastasis of different types of clinical tumors. We conclude that AKT not only regulates tumor glucose metabolism by directly phosphorylating HK1 and HK2, but also plays important roles in tumor progression, proliferation, and migration.

Bioorthogonal Labeling and Enrichment of Histone Monoaminylation Reveal Its Accumulation and Regulatory Function in Cancer Cell Chromatin.

Histone monoaminylation (i.e., serotonylation and dopaminylation) is an emerging category of epigenetic mark occurring on the fifth glutamine (Q5) residue of H3 N-terminal tail, which plays significant roles in gene transcription. Current analysis of histone monoaminylation is mainly based on site-specific antibodies and mass spectrometry, which either lacks high resolution or is time-consuming. In this study, we report the development of chemical probes for bioorthogonal labeling and enrichment of histone serotonylation and dopaminylation. These probes were successfully applied for the monoaminylation analysis of in vitro biochemical assays, cells, and tissue samples. The enrichment of monoaminylated histones by the probes further confirmed the crosstalk between H3Q5 monoaminylation and H3K4 methylation. Finally, combining the ex vivo and in vitro analyses based on the developed probes, we have shown that both histone serotonylation and dopaminylation are highly enriched in tumor tissues that overexpress transglutaminase 2 (TGM2) and regulate the three-dimensional architecture of cellular chromatin.

Chemical Proteomic Profiling of Protein Dopaminylation in Colorectal Cancer Cells.

Histone dopaminylation is a newly identified epigenetic mark that plays a role in the regulation of gene transcription, where an isopeptide bond is formed between the fifth amino acid of H3 (i.e., glutamine) and dopamine. Recently, we developed a chemical probe to specifically label and enrich histone dopaminylation via bioorthogonal chemistry. Given this powerful tool, we found that histone H3 glutamine 5 dopaminylation (H3Q5dop) was highly enriched in colorectal tumors, which could be attributed to the high expression level of its regulator, transglutaminase 2 (TGM2), in colon cancer cells. Due to the enzyme promiscuity of TGM2, nonhistone proteins have also been identified as dopaminylation targets; however, the dopaminylated proteome in cancer cells still remains elusive. Here, we utilized our chemical probe to enrich dopaminylated proteins from colorectal cancer cells in a bioorthogonal manner and performed the chemical proteomics analysis. Therefore, 425 dopaminylated proteins were identified, many of which are involved in nucleic acid metabolism and transcription pathways. More importantly, a number of dopaminylation sites were identified and attributed to the successful application of our chemical probe. Overall, these findings shed light on the significant association between cellular protein dopaminylation and cancer development, further suggesting that targeting these pathways may become a promising anticancer strategy.

Clinical features and treatment of heterotopic pancreas in children: a multi-center retrospective study.

OBJECTIVE: Heterotopic pancreas, an uncommon condition in children, can present with diagnostic and treatment challenges. This study aimed to evaluate the clinical features and treatment options for this disorder in pediatric patients. METHODS: We conducted a retrospective analysis, including patients diagnosed with heterotopic pancreas at four tertiary hospitals between January 2000 and June 2022. Patients were categorized into symptomatic and asymptomatic groups based on clinical presentation. Clinical parameters, including age at surgery, lesion size and site, surgical or endoscopic approach, pathological findings, and outcome, were statistically analyzed. RESULTS: The study included 88 patients with heterotopic pancreas. Among them, 22 were symptomatic, and 41 were aged one year or younger. The heterotopic pancreas was commonly located in Meckel's diverticulum (46.59%), jejunum (20.45%), umbilicus (10.23%),ileum (7.95%), and stomach (6.82%). Sixty-six patients had concomitant diseases. Thirty-three patients had heterotopic pancreas located in the Meckel's diverticulum, with 80.49% of cases accompanied by gastric mucosa heterotopia (GMH). Patients without accompanying GMH had a higher prevalence of heterotopic pancreas-related symptoms (75%). Treatment modalities included removal of the lesions by open surgery, laparoscopic or laparoscopic assisted surgery, or endoscopic surgery based on patient's age, the lesion site and size, and coexisting diseases. CONCLUSIONS: Only one-fourth of the patients with heterotopic pancreas presented with symptoms. Those located in the Meckel's diverticulum have commonly accompanying GMH. Open surgical, laparoscopic surgical or endoscopic resection of the heterotopic pancreas is recommended due to potential complications. Future prospective multicenter studies are warranted to establish rational treatment options.

Combined effects of micron-sized polyvinyl chloride particles and copper on seed germination of perilla.

Microplastics (MPs) and copper (Cu) pollution coexist widely in cultivation environment. In this paper, polyvinyl chloride (PVC) were used to simulate the MPs exposure environment, and the combined effects of MPs + Cu on the germination of perilla seeds were analyzed. The results showed that low concentrations of Cu promoted seed germination, while medium to high concentrations exhibited inhibition and deteriorated the morphology of germinated seeds. The germination potential, germination index and vitality index of 8 mg • L-1 Cu treatment group with were 23.08%, 76.32% and 65.65%, respectively, of the control group. The addition of low concentration PVC increased the above indicators by 1.27, 1.15, and 1.35 times, respectively, while high concentration addition led to a decrease of 65.38%, 82.5%, and 66.44%, respectively. The addition of low concentration PVC reduced the amount of PVC attached to radicle. There was no significant change in germination rate. PVC treatment alone had no significant effect on germination. MPs + Cu inhibited seed germination, which was mainly reflected in the deterioration of seed morphology. Cu significantly enhanced antioxidant enzyme activity, increased reactive oxygen species (ROS) and MDA content. The addition of low concentration PVC enhanced SOD activity, reduced MDA and H2O2 content. The SOD activity of the Cu2+8 + PVC10 group was 4.05 and 1.35 times higher than that of the control group and Cu treatment group at their peak, respectively. At this time, the CAT activity of the Cu2+8 + PVC5000 group increased by 2.66 and 1.42 times, and the H2O2 content was 2.02 times higher than the control. Most of the above indicators reached their peak at 24 h. The activity of α-amylase was inhibited by different treatments, but ß-amylase activity, starch and soluble sugar content did not change regularly. The research results can provide new ideas for evaluating the impact of MPs + Cu combined pollution on perilla and its potential ecological risk.

Chemical proteomic profiling of protein dopaminylation in colorectal cancer cells.

Histone dopaminylation is a newly identified epigenetic mark that plays a role in the regulation of gene transcription, where an isopeptide bond is formed between the fifth amino acid residue of H3 ( i.e. , glutamine) and dopamine. In our previous studies, we discovered that the dynamics of this post-translational modification (including installation, removal, and replacement) were regulated by a single enzyme, transglutaminase 2 (TGM2), through reversible transamination. Recently, we developed a chemical probe to specifically label and enrich histone dopaminylation via bioorthogonal chemistry. Given this powerful tool, we found that histone H3 glutamine 5 dopaminylation (H3Q5dop) was highly enriched in colorectal tumors, which could be attributed to the high expression level of TGM2 in colon cancer cells. Due to the enzyme promiscuity of TGM2, non-histone proteins have also been identified as targets of dopaminylation on glutamine residues, however, the dopaminylated proteome in cancer cells still remains elusive. Here, we utilized our chemical probe to enrich dopaminylated proteins from colorectal cancer cells in a bioorthogonal manner and performed the chemical proteomics analysis. Therefore, 425 dopaminylated proteins were identified, many of which are involved in nucleic acid metabolism and transcription pathways. More importantly, a number of modification sites of these dopaminylated proteins were identified, attributed to the successful application of our chemical probe. Overall, these findings shed light on the significant association between cellular protein dopaminylation and cancer development, further suggesting that to block the installation of protein dopaminylation may become a promising anti-cancer strategy.

pH-Controlled chemoselective rapid azo-coupling reaction (CRACR) enables global profiling of serotonylation proteome in cancer cells.

Serotonylation has been identified as a novel protein post-translational modification (PTM) for decades, where an isopeptide bond is formed between the glutamine residue and serotonin through transamination. Transglutaminase 2 (also known as TGM2 or TGase2) was proven to act as the main writer enzyme for this PTM and a number of key regulatory proteins (including small GTPases, fibronectin, fibrinogen, serotonin transporter, and histone H3) have been characterized as the substrates of serotonylation. However, due to the lack of pan-specific antibody for serotonylated glutamine, the precise enrichment and proteomic profiling of serotonylation still remain challenging. In our previous research, we developed an aryldiazonium probe to label protein serotonylation in a bioorthogonal manner. This chemical biology tool can be utilized alternatively for the antibody-free enrichment of serotonylated proteins, which depends on a pH-controlled chemoselective rapid azo-coupling reaction (CRACR). Here, we report the application of a photoactive aryldiazonium-biotin probe for the global profiling of serotonylation proteome in cancer cells. Thus, over 500 serotonylated proteins were identified from HCT 116 cells. Importantly, a number of modification sites of these serotonylated proteins were determine, attributed to the successful application of our chemical proteomic approach. Overall, these findings provided new insights into the significant association between cellular protein serotonylation and cancer development, further suggesting that to target TGM2-mediated monoaminylation may serve as a promising strategy for cancer therapeutics.

Chemical proteomics approaches for protein post-translational modification studies.

The diversity and dynamics of proteins play essential roles in maintaining the basic constructions and functions of cells. The abundance of functional proteins is regulated by the transcription and translation processes, while the alternative splicing enables the same gene to generate distinct protein isoforms of different lengths. Beyond the transcriptional and translational regulations, post-translational modifications (PTMs) are able to further expand the diversity and functional scope of proteins. PTMs have been shown to make significant changes in the surface charges, structures, activation states, and interactome of proteins. Due to the functional complexity, highly dynamic nature, and low presence percentage, the study of protein PTMs remains challenging. Here we summarize and discuss the major chemical biology tools and chemical proteomics approaches to enrich and investigate the protein PTM of interest.

Bioorthogonal labeling and enrichment of histone monoaminylation reveal its accumulation and regulatory function in cancer cell chromatin.

Histone monoaminylation ( i . e ., serotonylation and dopaminylation) is an emerging category of epigenetic mark occurring on the fifth glutamine (Q5) residue of H3 N-terminal tail, which plays significant roles in gene transcription. Current analysis of histone monoaminylation is mainly based on site-specific antibodies and mass spectrometry, which either lacks high resolution or is time-consuming. In this study, we report the development of chemical probes for bioorthogonal labeling and enrichment of histone serotonylation and dopaminylation. These probes were successfully applied for the monoaminylation analysis of in vitro biochemical assays, cells, and tissue samples. The enrichment of monoaminylated histones by the probes further confirmed the crosstalk between H3Q5 monoaminylation and H3K4 methylation. Finally, combining the ex vivo and in vitro analyses based on the developed probes, we have shown that both histone serotonylation and dopaminylation are highly enriched in tumor tissues that overexpress transglutaminase 2 (TGM2) and regulate the three-dimensional architecture of cellular chromatin.

Extensive Analysis of Mulberry (Morus rubra L.) Polysaccharides with Different Maturities by Using Two-Step Extraction and LC/QqQ-MS.

A primary challenge of polysaccharide analysis is the need for comprehensive extraction and characterization methods. In this study, mulberry polysaccharides at different maturities were fully extracted through a two-step process involving ethylenediaminetetraacetic acid (EDTA) and sodium hydroxide (NaOH), and their structures were determined by a combination analysis of monosaccharides and glycosidic linkages based on liquid chromatography triple quadrupole mass spectrometry (LC/QqQ-MS). The results indicate mulberry polysaccharides mainly contain highly branched pectic polysaccharides, (1,3,6)-linked glucan, xylan, and xyloglucan, but the content of different portions varies at different maturity stages. HG decreases from 19.12 and 19.14% (green mulberry) to 9.80 and 6.08% (red mulberry) but increases to 17.83 and 11.83% as mulberry transitioned from red to black. In contrast, the contents of glucan showed opposite trends. When mulberry turns red to black, the RG-I arabinan chains decrease from 47.75 and 28.86% to 13.16 and 12.72%, while the galactan side chains increase from 1.18 and 1.91 to 8.3 and 6.49%, xylan and xyloglucan show an increase in content. Overall, the two-step extraction combined with LC/QqQ-MS provides a new strategy for extensive analysis of complex plant polysaccharides.

Pan-cancer and multi-omics analyses revealed the diagnostic and prognostic value of BAZ2A in liver cancer.

BAZ2A, an epigenetic regulatory factor that affects ribosomal RNA transcription, has been shown to be highly expressed in several cancers and promotes tumor cell migration. This study explored the expression and mechanism of BAZ2A in tumorigenesis at the pan-cancer level. The Cancer Genome Atlas, Gene Expression Omnibus databases and TIMER2.0, cBioPortal and other tools were used to analyze the level of expression of BAZ2A in various tumor tissues and to examine the relationship between BAZ2A and survival, prognosis, mutation and immune invasion. In vitro experiments were performed to assess the function of BAZ2A in cancer cells. Using combined transcriptome and proteome analysis, we examined the possible mechanism of BAZ2A in tumors. BAZ2A exhibited high expression levels in multiple tumor tissues and displayed a significant association with cancer patient prognosis. The main type of BAZ2A genetic variation in cancer is gene mutation. Downregulation of BAZ2A inhibited proliferation, migration, and invasion and promoted apoptosis in LM6 liver cancer cell. The mechanism of BAZ2A in cancer development may involve lipid metabolism. These results help expand our understanding of BAZ2A in tumorigenesis and development and suggest BAZ2A may serve as a prognostic and diagnostic factor in several cancers.

TP53R175H mutation promotes breast cancer cell proliferation through CORO1A-P38 MAPK pathway regulation.

Breast cancer is the most commonly diagnosed cancer in women. Among all types, triple-negative breast cancer is particularly challenging to cure because of its high recurrence rates and invasive and metastatic capacity. Although numerous studies have explored the role of TP53 mutations in cancer, there is a dearth of research regarding the correlation between TP53 mutations and breast cancer cell proliferation. In this study, our aim was to examine the impact of TP53 mutations on the prognosis of patients with breast cancer bioinformatics techniques. To detect cell proliferation, a CCK8 assay was performed, and western blotting was used to identify the expression of p53, p38, and p-p38 proteins. Cellular mRNA sequencing was used to screen target genes of TP53 mutations, and molecular docking was performed to identify the drugs that could hinder the proliferation of breast cancer cells.The results showed that the TP53 mutation rate is higher in patients with triple-negative breast cancer than non-triple-negative breast cancer, and those with TP53 mutations tended to have a poorer prognosis than those without. Patients with R175H site mutations also had shorter survival times than those without. Cytological experiments revealed that the TP53R175H mutation increases the rate of breast cancer cell proliferation. In conjunction with this, CORO1A was found to be a downstream target of TP53 mutations, and it was determined to promote breast cancer cell proliferation. Moreover, CORO1A overexpression resulted in the downregulation of p-p38 levels. Molecular docking studies further revealed that tea polyphenols can inhibit breast cancer proliferation by binding to p53.

Online public concern about allergic rhinitis and its association with COVID-19 and air quality in China: an informative epidemiological study using Baidu index.

BACKGROUND: Allergic rhinitis is a common health concern that affects quality of life. This study aims to examine the online search trends of allergic rhinitis in China before and after the COVID-19 epidemic and to explore the association between the daily air quality and online search volumes of allergic rhinitis in Beijing. METHODS: We extracted the online search data of allergic rhinitis-related keywords from the Baidu index database from January 23, 2017 to June 23, 2022. We analyzed and compared the temporal distribution of online search behaviors across different themes of allergic rhinitis before and after the COVID-19 pandemic in mainland China, using the Baidu search index (BSI). We also obtained the air quality index (AQI) data in Beijing and assessed its correlation with daily BSIs of allergic rhinitis. RESULTS: The online search for allergic rhinitis in China showed significant seasonal variations, with two peaks each year in spring from March to May and autumn from August and October. The BSI of total allergic rhinitis-related searches increased gradually from 2017 to 2019, reaching a peak in April 2019, and declined after the COVID-19 pandemic, especially in the first half of 2020. The BSI for all allergic rhinitis themes was significantly lower after the COVID-19 pandemic than before (all p values < 0.05). The results also revealed that, in Beijing, there was a significant negative association between daily BSI and AQI for each allergic rhinitis theme during the original variant strain epidemic period and a significant positive correlation during the Omicron variant period. CONCLUSION: Both air quality and the interventions used for COVID-19 pandemic, including national and local quarantines and mask wearing behaviors, may have affected the incidence and public concern about allergic rhinitis in China. The online search trends can serve as a valuable tool for tracking real-time public concerns about allergic rhinitis. By complementing traditional disease monitoring systems of health departments, these search trends can also offer insights into the patterns of disease outbreaks. Additionally, they can provide references and suggestions regarding the public's knowledge demands related to allergic rhinitis, which can further be instrumental in developing targeted strategies to enhance population-based disease education on allergic diseases.

Inorganic Sodium Solid Electrolytes: Structure Design, Interface Engineering and Application.

All-solid-state sodium batteries (ASSSBs) are particularly attractive for large-scale energy storage and electric vehicles due to their exceptional safety, abundant resource availability, and cost-effectiveness. The growing demand for ASSSBs underscores the significance of sodium solid electrolytes; However, the existed challenges of sodium solid electrolytes hinder their practical application despite continuous research efforts. Herein, recent advancements and the challenges for sodium solid electrolytes from material to battery level are reviewed. The in-depth understanding of their fundamental properties, synthesis techniques, crystal structures and recent breakthroughs is presented. Moreover, critical challenges on inorganic sodium solid electrolytes are emphasized, including the imperative need to enhance ionic conductivity, fortifying interfacial compatibility with anode/cathode materials, and addressing dendrite formation issues. Finally, potential applications of these inorganic sodium solid electrolytes are explored in ASSSBs and emerging battery systems, offering insights into future research directions.

Memory T cells effectively recognize the SARS-CoV-2 hypermutated BA.2.86 variant.

T cells are critical in mediating the early control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection. However, it remains unknown whether memory T cells can effectively cross-recognize new SARS-CoV-2 variants with a broad array of mutations, such as the emergent hypermutated BA.2.86 variant. Here, we report in two separate cohorts, including healthy controls and individuals with chronic lymphocytic leukemia, that SARS-CoV-2 spike-specific CD4+ and CD8+ T cells induced by prior infection or vaccination demonstrate resilient immune recognition of BA.2.86. In both cohorts, we found largely preserved SARS-CoV-2 spike-specific CD4+ and CD8+ T cell magnitudes against mutated spike epitopes of BA.2.86. Functional analysis confirmed that both cytokine expression and proliferative capacity of SARS-CoV-2 spike-specific T cells to BA.2.86-mutated spike epitopes are similarly sustained. In summary, our findings indicate that memory CD4+ and CD8+ T cells continue to provide cell-mediated immune recognition to highly mutated emerging variants such as BA.2.86.

A Kano model-based demand analysis and perceived barriers of pulmonary rehabilitation interventions for patients with chronic obstructive pulmonary disease in China.

BACKGROUND: Pulmonary rehabilitation (PR) has been recognized to be an effective therapy for chronic obstructive pulmonary disease (COPD). However, in China, the application of PR interventions is still less promoted. Therefore, this cross-sectional study aimed to understand COPD patients' intention to receive PR, capture the potential personal, social and environmental barriers preventing their willingness of receiving PR, and eventually identify demanding PR services with the highest priority from patients' point of view. METHODS: In total 237 COPD patients were recruited from 8 health care facilities in Zhejiang, China. A self-designed questionnaire was applied to investigate patients' intention to participate in PR and potentially associated factors, including personal dimension such as personal awareness, demographic factors, COPD status and health-related literacy/behaviors, as well as social policies and perceived environmental barriers. The demand questionnaire of PR interventions based on the Kano model was further adopted. RESULTS: Among the 237 COPD patients, 75.1% of COPD patients were willing to participate in PR interventions, while only 62.9% of the investigated patients had heard of PR interventions. Over 90% of patients believed that the cost of PR services and the ratio of medical insurance reimbursement were potential obstacles hindering them from accepting PR services. The multiple linear regression analysis indicated that the PR skills of medical staff, knowledge promotion and public education levels of PR in the community, patients' transportation concerns and degree of support from family and friends were significantly associated with willingness of participation in PR interventions. By using the Kano model, the top 9 most-requisite PR services (i.e., one-dimensional qualities) were identified from patients' point of view, which are mainly diet guidance, education interventions, psychological interventions and lower limb exercise interventions. Subgroup analysis also revealed that patients' demographics, such as breathlessness level, age, education and income levels, could influence their choice of priorities for PR services, especially services related to exercise interventions, respiratory muscle training, oxygen therapy and expectoration. CONCLUSIONS: This study suggested that PR-related knowledge education among patients and their family, as well as providing basic package of PR services with the most-requisite PR items to COPD patients, were considerable approaches to promote PR attendance in the future.

Simultaneous detection of greenhouse gases CH4 and CO2 based on a dual differential photoacoustic spectroscopy system.

In addition to the atmospheric measurement, detection of dissolved carbon oxides and hydrocarbons in a water region is also an important aspect of greenhouse gas monitoring, such as CH4 and CO2. The first step of measuring dissolved gases is the separation process of water and gases. However, slow degassing efficiency is a big challenge which requires the gas detection technology itself with low gas consumption. Photoacoustic spectroscopy (PAS) is a good choice with advantages of high sensitivity, low gas consumption, and zero background, which has been rapidly developed in recent years and is expected to be applied in the field of dissolved gas detection. In this study, a miniaturized differential photoacoustic cell with a volume of 7.9 mL is designed for CH4 and CO2 detection, and a dual differential method with four microphones is proposed to enhance the photoacoustic signal. What we believe to be a new method increases photoacoustic signal by 4 times and improves the signal to noise ratio (SNR) over 10 times compared with the conventional single-microphone mode. Two distributed feedback (DFB) lasers at 1651 nm and 2004nm are employed to construct the PAS system for CH4 and CO2 detection respectively. Wavelength modulation spectroscopy (WMS) and 2nd harmonic demodulation techniques are applied to further improve the SNR. As a result, sensitivity of 0.44 ppm and 7.39 ppm for CH4 and CO2 are achieved respectively with an integration time of 10 s. Allan deviation analysis indicates that the sensitivity can be further improved to 42 ppb (NNEA=4.7×10-10cm-1WHz-1/2) for CH4 and 0.86 ppm (NNEA=5.3×10-10cm-1WHz-1/2) for CO2 when the integration time is extended to 1000 s.