Abuse of amphetamine-based stimulants is a primary public health concern. Recent studies have underscored a troubling escalation in the inappropriate use of prescription amphetamine-based stimulants. However, the neurophysiological mechanisms underlying the impact of acute methamphetamine exposure (AME) on sleep homeostasis remain to be explored. This study employed non-human primates and electroencephalogram (EEG) sleep staging to evaluate the influence of AME on neural oscillations. The primary focus was on alterations in spindles, delta oscillations, and slow oscillations (SOs) and their interactions as conduits through which AME influences sleep stability. AME predominantly diminishes sleep-spindle waves in the non-rapid eye movement 2 (NREM2) stage, and impacts SOs and delta waves differentially. Furthermore, the competitive relationships between SO/delta waves nesting with sleep spindles were selectively strengthened by methamphetamine. Complexity analysis also revealed that the SO-nested spindles had lost their ability to maintain sleep depth and stability. In summary, this finding could be one of the intrinsic electrophysiological mechanisms by which AME disrupted sleep homeostasis.
Animals ; Methamphetamine ; Electroencephalography ; Male ; Sleep/drug effects* ; Central Nervous System Stimulants ; Delta Rhythm/drug effects* ; Sleep Stages/drug effects*

Dysregulated RNA splicing is a well-recognized characteristic of colorectal cancer (CRC); however, its intricacies remain obscure, partly due to challenges in profiling full-length transcript variants at the single-cell level. Here, we employ high-depth long-read scRNA-seq to define the full-length transcriptome of colorectal epithelial cells in 12 CRC patients, revealing extensive isoform diversities and splicing alterations. Cancer cells exhibited increased transcript complexity, with widespread 3'-UTR shortening and reduced intron retention. Distinct splicing regulation patterns were observed between intrinsic-consensus molecular subtypes (iCMS), with iCMS3 displaying even higher splicing factor activities and more pronounced 3'-UTR shortening. Furthermore, we revealed substantial shifts in isoform usage that result in alterations of protein sequences from the same gene with distinct carcinogenic effects during tumorigenesis of CRC. Allele-specific expression analysis revealed dominant mutant allele expression in key oncogenes and tumor suppressors. Moreover, mutated PPIG was linked to widespread splicing dysregulation, and functional validation experiments confirmed its critical role in modulating RNA splicing and tumor-associated processes. Our findings highlight the transcriptomic plasticity in CRC and suggest novel candidate targets for splicing-based therapeutic strategies.
Humans ; Colorectal Neoplasms/metabolism* ; RNA Isoforms/metabolism* ; Single-Cell Analysis ; RNA Splicing ; Gene Expression Regulation, Neoplastic ; RNA, Neoplasm/metabolism* ; Transcriptome

Radiopharmaceuticals operate by combining radionuclides with carriers. The radiation energy emitted by radionuclides is utilized to selectively irradiate diseased tissues while minimizing damage to healthy tissues. In comparison to external beam radiation therapy, radionuclide drugs demonstrate research potential due to their biological targeting capabilities and reduced normal tissue toxicity. This article reviews the applications and research progress of radiopharmaceuticals in cancer treatment. Several key radionuclides are examined, including ²²³Ra, ⁹⁰Y, Lutetium-177 (¹⁷⁷Lu), ²¹²Pb, and Actinium-225 (²²⁵Ac). It also explores the current development trends of radiopharmaceuticals, encompassing the introduction of novel radionuclides, advancements in imaging technologies, integrated diagnosis and treatment approaches, and equipment-medication combinations. We review the progress in the development of new treatments, such as neutron capture therapy, proton therapy, and heavy ion therapy. Furthermore, we examine the challenges and breakthroughs associated with the clinical translation of radiopharmaceuticals and provide recommendations for the research and development of novel radionuclide drugs.
Humans ; Radiopharmaceuticals/therapeutic use* ; Neoplasms/radiotherapy* ; Radioisotopes/therapeutic use* ; Animals

Objective To observe the effects of electroacupuncture at"Neiguan"and"Gongsun"on autophagy and apoptosis related indexes of interstitial cells of Cajal(ICC)in rats with functional dyspepsia(FD);To explore its possible mechanism on improving gastrointestinal motility of FD.Methods Totally 32 SPF grade SD rats were randomly divided into blank group,model group,electroacupuncture group and Western medicine group,with 8 rats in each group.An FD model was constructed using a composite etiology modeling method.The electroacupuncture group received electroacupuncture at"Neiguan"and"Gongsun",while the Western medicine group received oral administration of mosapride once a day for 7 consecutive days.The general condition,body mass and average daily intake of rats were observed every week,and gastric emptying rate and small intestine propulsion rate were detected,transmission electron microscopy was used to observe the structure of gastric antrum ICC,Western blot was used to observe the expressions of c-kit,Beclin1,LC3Ⅱ/Ⅰ,p62,Caspase-3 protein in gastric antrum tissue,qPCR was used to observe the mRNA expressions of Beclin1,LC3Ⅱ/Ⅰ,p62 and c-kit in gastric antrum tissue,TUNEL staining was used to detect the apoptosis rate of cells in gastric antrum tissue.Results Compared with the blank group,the model group rats were mentally lethargic,clustered and curled up,with reduced activity,rough and dull hair,loose and unformed feces,reduced body mass and daily food intake(P<0.05),and gastric emptying rate and small intestine propulsion rate decreased(P<0.01),ICC mitochondria swelled and dissolved,with varying degrees of vacuolar formation,rough endoplasmic reticulum dilation and destruction,and a large number of autophagosomes,the expressions of Beclin1 and LC3 Ⅱ/Ⅰ protein and mRNA in gastric antrum tissue increased(P<0.01),the expressions of p62,c-kit protein and mRNA decreased(P<0.01),while Caspase-3 protein expression increased(P<0.01),and the apoptosis rate of gastric antral tissue cells increased(P<0.01).Compared with the model group,the condition of rats in electroacupuncture group and the Western medicine group were improved,with increased responsiveness,increased mobility,neat hair,formed feces,increased body mass and daily food intake(P<0.01),and gastric emptying rate and small intestine propulsion rate increase(P<0.01),a normal ICC structure,and a small amount of autophagosomes were still visible,the expressions of Beclin1,LC3Ⅱ/Ⅰ protein and mRNA in gastric antrum tissue decreased(P<0.01),the expressions of p62,c-kit protein and mRNA increased(P<0.01),while Caspase-3 protein expression decreased(P<0.01),and the apoptosis rate of gastric antral tissue cells decreased(P<0.01).There was no statistically significant difference in various indicators between electroacupuncture group and Western medicine group(P>0.05).Conclusion Electroacupuncture at"Neiguan"and"Gongsun"can restore the number and structure of ICC and improve gastrointestinal motility,and its mechanism may be related to the inhibition of autophagy and apoptosis levels.

We surveyed tick species and their carried pathogens for three important emerging zoonotic diseases(Babesiosis,Lyme disease,and fever with thrombocytopenia syndrome)at border areas between China and Mongolia,to provide data support for the construction of a database on cross-border transmission of important tick-borne diseases and the prevention and control of zoonotic tick-borne diseases in border areas.In 2023-2024,tick samples were collected from 12 border areas along the Sino-Mongolian bor-der,and tick species were identified according to morphology and molecular biology,then tested for the pathogens of three newly emerging zoonotic diseases with real-time fluorescence quantitative PCR and conventional PCR.Positive samples were verified through gene sequencing.A total of 2 477 ticks of five genera and nine species were collected from the border areas of China and Mongolia.The dominant tick species were identified as the grassland leatherback tick,the full-groove tick,and the small glaucous-eyed tick.The overall positivity rates of ticks carrying Babesia,Lyme disease spirochetes,and fever with thrombocytopenia virus in the 12 border ar-eas were 8.32%,11.59%,and 0%,respectively.Babesia,the most widely distributed tick species,was detected in ticks at eight areas in the eastern,central,and western parts of the China-Mongolia border.This species was found in eastern,central,and western ports along the Sino-Mongolian border;showed tick positivity rates of 0.37%-38.82%;and was most frequently carried by full-groove hard ticks.Spirochetes of Lyme disease were the next most widely distributed,and were detected in samples from four port areas,primarily in the eastern ports along the Sino-Mongolian border;97.2%of positive samples were detected in full-groove hard ticks.Zoonotic Babe-sia spp.were widely distributed in the border crossing areas of China and Mongolia,and included five species of Babesia microti,Ba-besia venatorum,and Babesia divergens,whereas the Lyme disease spirochetes were prevalent mainly in the east,including five geno-types of Borreliella garinii,Borreliella afzelii,and Borrelia burgdorferi sensu stricto.Co-infection with Babesia and Lyme disease spiro-chetes was present in hard ticks throughout the groove,and co-infected samples accounted for 74.27%of Babesia positive and 53.31%of Lyme disease positive samples.Thus,Babesia and Lyme disease spirochetes were found to be important tick-borne emerging zoo-notic pathogens in the Sino-Mongolian border crossing areas,the infected ticks were primarily full-grooved hard ticks,and co-infections were found.

Objective:To investigate the distribution of iodine in drinking water and the iodine nutrition status of key populations in Boxing County of Shandong Province, and to provide a basis for continuous elimination of iodine deficiency disorders and scientific iodine supplementation.Methods:In 2021, in the historical iodine deficiency towns (districts, referred to as towns) in Boxing County, one water sample of centralized water supply terminal water of each administrative village (neighborhood committee) was collected for water iodine testing. Using stratified cluster sampling method, the historical iodine deficiency areas in Boxing County were divided into 5 areas according to east, west, south, north and center. One town was randomly selected from each area, 20 pregnant women and 40 non-boarding students aged 8 - 10 from a primary school were randomly selected from each town. Thirty pregnant women and 100 students were selected from each of the two historical high iodine towns, and random urine samples were collected from the above-mentioned population for urinary iodine detection and analysis.Results:A total of 329 water samples were collected, and the median water iodine was 10.9 μg/L. Of these, 267 samples (81.2%) were < 40 μg/L, 33 samples (10.0%) were among 40 - 100 μg/L, and 29 samples (8.8%) were > 100 μg/L. A total of 410 urine samples were collected from children, and the median urinary iodine was 162.0 μg/L. The median urinary iodine of children in different towns was compared, and the difference was statistically significant ( H = 86.34, P < 0.001). A total of 109 urine samples were collected from pregnant women, and the median urinary iodine was 57.4 μg/L. The median urinary iodine of pregnant women in different towns were compared, and the difference was statistically significant ( H = 38.35, P < 0.001). Conclusions:The distribution of iodine in drinking water in Boxing County is complex, with areas with high iodine, iodine deficiency, and suitable iodine sources coexisting. Children's iodine nutrition is at an appropriate level, but pregnant women's iodine nutrition is at a deficiency level. Relevant departments should strengthen health promotion, and each region should formulate iodized salt supply strategies based on actual conditions. At the same time, special attention should be paid to the iodine nutrition status of pregnant women.

We surveyed tick species and their carried pathogens for three important emerging zoonotic diseases(Babesiosis,Lyme disease,and fever with thrombocytopenia syndrome)at border areas between China and Mongolia,to provide data support for the construction of a database on cross-border transmission of important tick-borne diseases and the prevention and control of zoonotic tick-borne diseases in border areas.In 2023-2024,tick samples were collected from 12 border areas along the Sino-Mongolian bor-der,and tick species were identified according to morphology and molecular biology,then tested for the pathogens of three newly emerging zoonotic diseases with real-time fluorescence quantitative PCR and conventional PCR.Positive samples were verified through gene sequencing.A total of 2 477 ticks of five genera and nine species were collected from the border areas of China and Mongolia.The dominant tick species were identified as the grassland leatherback tick,the full-groove tick,and the small glaucous-eyed tick.The overall positivity rates of ticks carrying Babesia,Lyme disease spirochetes,and fever with thrombocytopenia virus in the 12 border ar-eas were 8.32%,11.59%,and 0%,respectively.Babesia,the most widely distributed tick species,was detected in ticks at eight areas in the eastern,central,and western parts of the China-Mongolia border.This species was found in eastern,central,and western ports along the Sino-Mongolian border;showed tick positivity rates of 0.37%-38.82%;and was most frequently carried by full-groove hard ticks.Spirochetes of Lyme disease were the next most widely distributed,and were detected in samples from four port areas,primarily in the eastern ports along the Sino-Mongolian border;97.2%of positive samples were detected in full-groove hard ticks.Zoonotic Babe-sia spp.were widely distributed in the border crossing areas of China and Mongolia,and included five species of Babesia microti,Ba-besia venatorum,and Babesia divergens,whereas the Lyme disease spirochetes were prevalent mainly in the east,including five geno-types of Borreliella garinii,Borreliella afzelii,and Borrelia burgdorferi sensu stricto.Co-infection with Babesia and Lyme disease spiro-chetes was present in hard ticks throughout the groove,and co-infected samples accounted for 74.27%of Babesia positive and 53.31%of Lyme disease positive samples.Thus,Babesia and Lyme disease spirochetes were found to be important tick-borne emerging zoo-notic pathogens in the Sino-Mongolian border crossing areas,the infected ticks were primarily full-grooved hard ticks,and co-infections were found.

Objective:To investigate the distribution of iodine in drinking water and the iodine nutrition status of key populations in Boxing County of Shandong Province, and to provide a basis for continuous elimination of iodine deficiency disorders and scientific iodine supplementation.Methods:In 2021, in the historical iodine deficiency towns (districts, referred to as towns) in Boxing County, one water sample of centralized water supply terminal water of each administrative village (neighborhood committee) was collected for water iodine testing. Using stratified cluster sampling method, the historical iodine deficiency areas in Boxing County were divided into 5 areas according to east, west, south, north and center. One town was randomly selected from each area, 20 pregnant women and 40 non-boarding students aged 8 - 10 from a primary school were randomly selected from each town. Thirty pregnant women and 100 students were selected from each of the two historical high iodine towns, and random urine samples were collected from the above-mentioned population for urinary iodine detection and analysis.Results:A total of 329 water samples were collected, and the median water iodine was 10.9 μg/L. Of these, 267 samples (81.2%) were < 40 μg/L, 33 samples (10.0%) were among 40 - 100 μg/L, and 29 samples (8.8%) were > 100 μg/L. A total of 410 urine samples were collected from children, and the median urinary iodine was 162.0 μg/L. The median urinary iodine of children in different towns was compared, and the difference was statistically significant ( H = 86.34, P < 0.001). A total of 109 urine samples were collected from pregnant women, and the median urinary iodine was 57.4 μg/L. The median urinary iodine of pregnant women in different towns were compared, and the difference was statistically significant ( H = 38.35, P < 0.001). Conclusions:The distribution of iodine in drinking water in Boxing County is complex, with areas with high iodine, iodine deficiency, and suitable iodine sources coexisting. Children's iodine nutrition is at an appropriate level, but pregnant women's iodine nutrition is at a deficiency level. Relevant departments should strengthen health promotion, and each region should formulate iodized salt supply strategies based on actual conditions. At the same time, special attention should be paid to the iodine nutrition status of pregnant women.

Objective To observe the effects of electroacupuncture at"Neiguan"and"Gongsun"on autophagy and apoptosis related indexes of interstitial cells of Cajal(ICC)in rats with functional dyspepsia(FD);To explore its possible mechanism on improving gastrointestinal motility of FD.Methods Totally 32 SPF grade SD rats were randomly divided into blank group,model group,electroacupuncture group and Western medicine group,with 8 rats in each group.An FD model was constructed using a composite etiology modeling method.The electroacupuncture group received electroacupuncture at"Neiguan"and"Gongsun",while the Western medicine group received oral administration of mosapride once a day for 7 consecutive days.The general condition,body mass and average daily intake of rats were observed every week,and gastric emptying rate and small intestine propulsion rate were detected,transmission electron microscopy was used to observe the structure of gastric antrum ICC,Western blot was used to observe the expressions of c-kit,Beclin1,LC3Ⅱ/Ⅰ,p62,Caspase-3 protein in gastric antrum tissue,qPCR was used to observe the mRNA expressions of Beclin1,LC3Ⅱ/Ⅰ,p62 and c-kit in gastric antrum tissue,TUNEL staining was used to detect the apoptosis rate of cells in gastric antrum tissue.Results Compared with the blank group,the model group rats were mentally lethargic,clustered and curled up,with reduced activity,rough and dull hair,loose and unformed feces,reduced body mass and daily food intake(P<0.05),and gastric emptying rate and small intestine propulsion rate decreased(P<0.01),ICC mitochondria swelled and dissolved,with varying degrees of vacuolar formation,rough endoplasmic reticulum dilation and destruction,and a large number of autophagosomes,the expressions of Beclin1 and LC3 Ⅱ/Ⅰ protein and mRNA in gastric antrum tissue increased(P<0.01),the expressions of p62,c-kit protein and mRNA decreased(P<0.01),while Caspase-3 protein expression increased(P<0.01),and the apoptosis rate of gastric antral tissue cells increased(P<0.01).Compared with the model group,the condition of rats in electroacupuncture group and the Western medicine group were improved,with increased responsiveness,increased mobility,neat hair,formed feces,increased body mass and daily food intake(P<0.01),and gastric emptying rate and small intestine propulsion rate increase(P<0.01),a normal ICC structure,and a small amount of autophagosomes were still visible,the expressions of Beclin1,LC3Ⅱ/Ⅰ protein and mRNA in gastric antrum tissue decreased(P<0.01),the expressions of p62,c-kit protein and mRNA increased(P<0.01),while Caspase-3 protein expression decreased(P<0.01),and the apoptosis rate of gastric antral tissue cells decreased(P<0.01).There was no statistically significant difference in various indicators between electroacupuncture group and Western medicine group(P>0.05).Conclusion Electroacupuncture at"Neiguan"and"Gongsun"can restore the number and structure of ICC and improve gastrointestinal motility,and its mechanism may be related to the inhibition of autophagy and apoptosis levels.

Objective:To investigate the effect of fecal microbiota transplantation(FMT)on unilateral ureteral obstruction(UUO)-induced renal fibrosis in mice.Methods:Male C57BL/6J mice were randomly divided into the control group,UUO group,UUO+FMT group and myeloid-derived suppressor cells(MDSCs)transfer group.The latter 3 groups were constructed renal fibrosis models by UUO,the UUO+FMT group received FMT from control mice after UUO surgery,and the MDSCs transfer group underwent splenectomy and intravenous injection of MDSCs from the peripheral blood of the UUO+FMT group.Renal tissue specimens were collected at 14 d after UUO for HE and Masson staining.TNF-α and IL-10 expression levels were detected by real-time fluorescence quantitative PCR(qRT-PCR),Western blot and immunofluorescence staining.Results:HE staining showed that the renal tissue structure of the control group was normal.The UUO group showed significant dilatation of renal tubules accompanied by obvious inflammatory cell infiltration.However,the renal lesions in the UUO+FMT group and MDSCs transfer group were significantly improved compared with those in the UUO group.Masson staining showed that the positive area of collagen deposition significantly increased in the UUO group compared with the control group,while the positive area of collagen deposition decreased in the UUO+FMT group and MDSCs transfer group compared with the UUO group.The results of qRT-PCR,Western blot and immunofluorescence showed that the expression levels of TNF-α and IL-10 were elevated in renal tissues of the UUO group compared with the control group.Compared with the UUO group,the expression level of TNF-α decreased while IL-10 increased in the UUO+FMT group and MDSCs transfer group.Conclusions:FMT reduces the expression of TNF-α and increase the expression of IL-10 in the kidney of UUO mice,and alleviates renal fibrosis.FMT may exert a nephroprotective effect by regulating MDSCs.